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  • Costs and health effects of CT perfusion-based selection for endovascular thrombectomy within 6 hours of stroke onset: a model-based health economic evaluation

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Cerebrovascular disease
Original research
Costs and health effects of CT perfusion-based selection for endovascular thrombectomy within 6 hours of stroke onset: a model-based health economic evaluation
  1. Henk van Voorst1,2,
  2. Jan W Hoving1,
  3. Miou S Koopman1,
  4. Jasper D Daems3,4,
  5. Daan Peerlings5,
  6. Erik Buskens6,
  7. Hester Lingsma7,
  8. Henk A Marquering1,8,
  9. Hugo W A M de Jong9,
  10. Olvert A Berkhemer10,10,
  11. Wim H van Zwam11,
  12. Marianne A A van Walderveen12,
  13. Ido R van den Wijngaard13,14,
  14. Diederik W J Dippel15,
  15. Albert J Yoo16,
  16. Bruce Campbell17,
  17. Wolfgang G Kunz18,
  18. Charles B Majoie1,
  19. Bart J Emmer1,
  20. CLEOPATRA,
  21. MR CLEAN Registry
  22. CONTRAST Consortium Investigators
        1. 1 Department of Radiology and Nuclear Medicine, Amsterdam UMC Location AMC, Amsterdam, North Holland, The Netherlands
        2. 2 Department of Biomedical Engineering and Physics, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands
        3. 3 Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands
        4. 4 Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
        5. 5 Department of Radiology, University Medical Center Utrecht, Utrecht, Utrecht, The Netherlands
        6. 6 Epidemiology, University Medical Centre Groningen, Groningen, Groningen, The Netherlands
        7. 7 Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
        8. 8 Biomedical Engineering and Physics, Amsterdam UMC Location AMC, Amsterdam, North Holland, The Netherlands
        9. 9 UMC Utrecht, Utrecht, Utrecht, The Netherlands
        10. 10 Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands
        11. 11 Radiology, Maastricht University Medical Center, Maastricht, The Netherlands
        12. 12 Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands
        13. 13 Neurology, HMC Westeinde, The Hague, Zuid-Holland, The Netherlands
        14. 14 Neurology, Leiden University, Leiden, The Netherlands
        15. 15 Neurology, Erasmus Mc University Medical Center, Rotterdam, The Netherlands
        16. 16 Neurointervention, Texas Stroke Institute, Plano, Texas, USA
        17. 17 The Royal Melbourne Hospital, Parkville, Melbourne, Australia
        18. 18 Ludwig Maximilians University Munich, Munich, Germany
        1. Correspondence to Dr Henk van Voorst, Department of Radiology and Nuclear Medicine, Amsterdam UMC Location AMC, Amsterdam, 1034, The Netherlands; h.vanvoorst{at}amsterdamumc.nl

        Abstract

        Background Although CT perfusion (CTP) is often incorporated in acute stroke workflows, it remains largely unclear what the associated costs and health implications are in the long run of CTP-based patient selection for endovascular treatment (EVT) in patients presenting within 6 hours after symptom onset with a large vessel occlusion.

        Methods Patients with a large vessel occlusion were included from a Dutch nationwide cohort (n=703) if CTP imaging was performed before EVT within 6 hours after stroke onset. Simulated cost and health effects during 5 and 10 years follow-up were compared between CTP based patient selection for EVT and providing EVT to all patients. Outcome measures were the net monetary benefit at a willingness-to-pay of €80 000 per quality-adjusted life year, incremental cost-effectiveness ratio), difference in costs from a healthcare payer perspective (ΔCosts) and quality-adjusted life years (ΔQALY) per 1000 patients for 1000 model iterations as outcomes.

        Results Compared with treating all patients, CTP-based selection for EVT at the optimised ischaemic core volume (ICV≥110 mL) or core-penumbra mismatch ratio (MMR≤1.4) thresholds resulted in losses of health (median ΔQALYs for ICV≥110 mL: −3.3 (IQR: −5.9 to −1.1), for MMR≤1.4: 0.0 (IQR: −1.3 to 0.0)) with median ΔCosts for ICV≥110 mL of −€348 966 (IQR: −€712 406 to −€51 158) and for MMR≤1.4 of €266 513 (IQR: €229 403 to €380 110)) per 1000 patients. Sensitivity analyses did not yield any scenarios for CTP-based selection of patients for EVT that were cost-effective for improving health, including patients aged ≥80 years

        Conclusion In EVT-eligible patients presenting within 6 hours after symptom onset, excluding patients based on CTP parameters was not cost-effective and could potentially harm patients.

        • STROKE
        • HEALTH ECONOMICS
        • NEURORADIOLOGY
        • IMAGE ANALYSIS

        Data availability statement

        Data are available upon reasonable request. The complete de-identified patient data sets from the MR CLEAN-NO IV, and MR CLEAN-MED trials will be available from 18 months after publication until 15 years from publication. Data can be obtained from https://www.contrast-consortium.nl/data-request-form/. The data will be made available to researchers who are CONTRAST consortium members or collaborators, and whose proposed use of the data has been approved by the CONTRAST data access and writing committee. The data will be made available for specified purposes, as defined in the substudy proposal and approved by the CONTRAST data access and writing committee. The data will be made available after approval of the proposal by the CONTRAST data access and writing committee. To ensure publication transparency and quality, researchers should adhere to the CONTRAST publication policy, accessible on https://www.contrast-consortium.nl/publication-policy-contrast/. For the patients included in the MR CLEAN Registry and the local cohort, individual patient data cannot be made available under Dutch law since we did not obtain patient approval for sharing individual patient data. All syntax files and output of statistical analyses are available on reasonable request to the corresponding author.

        https://doi.org/10.1136/jnnp-2023-331862

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          Data availability statement

          Data are available upon reasonable request. The complete de-identified patient data sets from the MR CLEAN-NO IV, and MR CLEAN-MED trials will be available from 18 months after publication until 15 years from publication. Data can be obtained from https://www.contrast-consortium.nl/data-request-form/. The data will be made available to researchers who are CONTRAST consortium members or collaborators, and whose proposed use of the data has been approved by the CONTRAST data access and writing committee. The data will be made available for specified purposes, as defined in the substudy proposal and approved by the CONTRAST data access and writing committee. The data will be made available after approval of the proposal by the CONTRAST data access and writing committee. To ensure publication transparency and quality, researchers should adhere to the CONTRAST publication policy, accessible on https://www.contrast-consortium.nl/publication-policy-contrast/. For the patients included in the MR CLEAN Registry and the local cohort, individual patient data cannot be made available under Dutch law since we did not obtain patient approval for sharing individual patient data. All syntax files and output of statistical analyses are available on reasonable request to the corresponding author.

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          Footnotes

          • HvV and JWH contributed equally.

          • Collaborators CLEOPATRA: CLEOPATRA Principal Investigators: Bart Emmer (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Charles Majoie (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Henk Marquering (PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Hugo de Jong (PhD) (University Medical Center Utrecht, Utrecht, the Netherlands), Hester Lingsma (PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Diederik Dippel (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands). Study coordinators: Arnolt-Jan Hoving (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Henk van Voorst (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Daan Peerlings (MSc) (University Medical Center Utrecht, Utrecht, the Netherlands), Jasper Daems (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Miou Koopman (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands). Local principal investigators (CONTRAST, MR CLEAN Registry, and CLEOPATRA): Jonathan Coutinho (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Bart van der Worp (MD, PhD) (University Medical Center Utrecht, Utrecht, the Netherlands), Rob Lo (MD, PhD) (University Medical Center Utrecht, Utrecht, the Netherlands), Jan Willem Dankbaar (MD, PhD) (University Medical Center Utrecht, Utrecht, the Netherlands), Bob Roozenbeek (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Adriaan van Es (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Pieter-Jan van Doormaal (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Jasper Martens (MD) (Rijnstate Hospital, Arnhem, the Netherlands), Jeanette Hofmeijer (MD, PhD) (Rijnstate Hospital, Arnhem, the Netherlands), Maarten Uyttenboogaart (MD, PhD) (University Medical Center Groningen, Groningen, the Netherlands), Reinoud Bokkers (MD, PhD) (University Medical Center Groningen, Groningen, the Netherlands), Marianne van Walderveen (MD, PhD) (Leiden University Medical Center, Leiden, the Netherlands), Marieke Wermer (MD, PhD) (Leiden University Medical Center, Leiden, the Netherlands), Lonneke Yo (MD, PhD) (Catharina Hospital, Eindhoven, the Netherlands), Koos Keizer (MD, PhD) (Catharina Hospital, Eindhoven, the Netherlands), Rob Gons (MD) (Catharina Hospital, Eindhoven, the Netherlands), Aad van der Lugt (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Julie Staals (MD, PhD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Wim van Zwam (MD, PhD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Inger de Ridder (MD, PhD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Karlijn de Laat (MD, PhD) (HagaZiekenhuis, the Hague, the Netherlands), Lukas van Dijk (MD, PhD) (HagaZiekenhuis, the Hague, the Netherlands), Jelis Boiten (MD, PhD) (Haaglanden Medical Center, the Hague, the Netherlands), Sebastiaan de Bruijn (MD, PhD) (HagaZiekenhuis, the Hague, the Netherlands), Geert Lycklama à Nijeholt (MD, PhD) (Haaglanden Medical Center, the Hague, the Netherlands), Ido van den Wijngaard (MD, PhD) (Haaglanden Medical Center, the Hague, the Netherlands), Paul de Kort (MD, PhD) (Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands), Michel Remmers (MD) (Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands), Anouk van Norden (MD) (Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands), Issam Boukrab (MD) (Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands), Julia van Tuijl (MD) (Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands), Hans Kortman (MD) (Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands), Anton Meijer (MD, PhD) (Radboud University Medical Center, Nijmegen, the Netherlands), Floris Schreuder (MD, PhD) (Radboud University Medical Center, Nijmegen, the Netherlands), Ewoud van Dijk (MD, PhD) (Radboud University Medical Center, Nijmegen, the Netherlands), Hieronymus Boogaarts (MD, PhD) (Radboud University Medical Center, Nijmegen, the Netherlands), Heleen den Hertog (MD, PhD) (Isala Klinieken, Zwolle, the Netherlands), Zwenneke Flach (MD) (Isala Klinieken, Zwolle, the Netherlands), Jan van den Berg (MD) (Isala Klinieken, Zwolle, the Netherlands), Boudewijn van Hasselt (MD) (Isala Klinieken, Zwolle, the Netherlands), Michel Remmers (MD) (Amphia Hospital, Breda, the Netherlands), Anouk van Norden (MD) (Amphia Hospital, Breda, the Netherlands), Farshad Imani (MD) (Amphia Hospital, Breda, the Netherlands), Otto Elgersma (MD, PhD) (Albert Schweitzer Hospital, Dordrecht, the Netherlands), Anouk Rozeman (MD) (Albert Schweitzer Hospital, Dordrecht, the Netherlands), Paul Brouwers (MD, PhD) (Medisch Spectrum Twente, Enschede, the Netherlands), Dick Gerrits (MD) (Medisch Spectrum Twente, Enschede, the Netherlands), Thomas Bulut (MD) (Medisch Spectrum Twente, Enschede, the Netherlands), Paul Brouwers (MD) (Medisch Spectrum Twente, Enschede, the Netherlands), Jan Albert Vos (MD, PhD) (St. Antonius Hospital, Nieuwegein, the Netherlands), Wouter Schonewille (MD, PhD) (St. Antonius Hospital, Nieuwegein, the Netherlands). CLEOPATRA Advisory Board: Albert Yoo (MD, PhD) (Texas Stroke Institute, Plano, TX, USA), Wolfgang Kunz (MD, PhD) (University Hospital, LMU Munich, Munich, Germany), Bruce Campbell (MD, PhD) (Melbourne Brain Center, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia). Trial Office Zorgevaluatie Nederland: Nienke Pannekoek (PhD) (Trialbureau Zorgevaluatie Nederland, Diemen, the Netherlands). Local trial collaborators: Executive and writing committee: Bart Emmer (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Charles Majoie (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Erik Buskens (MD, PhD) (University Medical Center Groningen, Groningen, the Netherlands), Hester Lingsma (PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Henk Marquering (PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Hugo de Jong (PhD) (University Medical Center Utrecht, Utrecht, the Netherlands), Olvert Berkhemer (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Wim van Zwam (MD, PhD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Marianne van Walderveen (MD, PhD) (Leiden University Medical Center, Leiden, the Netherlands), Ido van den Wijngaard (MD, PhD) (Haaglanden Medical Center, the Hague, the Netherlands), Aad van der Lugt (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Diederik Dippel (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Arnolt-Jan Hoving (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Henk van Voorst (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Daan Peerlings (MSc) (University Medical Center Utrecht, Utrecht, the Netherlands), Jasper Daems (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands). Trial statistician: Hester Lingsma (PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands). CONTRAST clinical trial collaborators: CONTRAST research leaders: Diederik Dippel (MD, PhD) (University Medical Center Utrecht, Utrecht, the Netherlands), Aad van der Lugt (MD, PhD) (University Medical Center Utrecht, Utrecht, the Netherlands), Charles Majoie (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Yvo Roos (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Robert van Oostenbrugge (MD, PhD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Wim van Zwam (MD, PhD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands). CONTRAST Imaging assessment committee: Charles Majoie (MD, PhD) – Chair (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Aad van der Lugt (MD, PhD) – Chair (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Wim van Zwam (MD, PhD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Linda Jacobi (MD, PhD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), René van den Berg, (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Ludo Beenen (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Bart Emmer (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Adriaan van Es, (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Pieter-Jan van Doormaal (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Geert Lycklama à Nijeholt (MD, PhD) (Haaglanden Medical Center, the Hague, the Netherlands), Ido van den Wijngaard (MD, PhD) (Haaglanden Medical Center, the Hague, the Netherlands), Albert Yoo (MD, PhD) (Texas Stroke Institute, Plano, TX, USA), Lonneke Yo (MD, PhD) (Catharina Hospital, Eindhoven, the Netherlands), Jasper Martens (MD, PhD) (Rijnstate Hospital, Arnhem, the Netherlands), Bas Hammer (MD, PhD) (HagaZiekenhuis, the Hague, the Netherlands), Stefan Roosendaal (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Anton Meijer (MD, PhD) (Radboud University Medical Center, Nijmegen, the Netherlands), Menno Krietemeijer (MD) (Catharina Hospital, Eindhoven, the Netherlands), Reinoud Bokkers (MD, PhD) (Rijnstate Hospital, Arnhem, the Netherlands), Anouk van der Hoorn (MD, PhD) (Rijnstate Hospital, Arnhem, the Netherlands), Dick Gerrits (MD) (Medisch Spectrum Twente, Enschede, the Netherlands). MR CLEAN Registry Imaging assessment committee: Charles Majoie (MD, PhD) – Chair (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Wim van Zwam (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Aad van der Lugt (University Medical Center Utrecht, Utrecht, the Netherlands), Geert Lycklama à Nijeholt (MD, PhD) (Haaglanden Medical Center, the Hague, the Netherlands), Marianne van Walderveen (MD, PhD) (Leiden University Medical Center, Leiden, the Netherlands), Marieke Sprengers (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Sjoer Jenniskens (MD, PhD) (Radboud University Medical Center, Nijmegen, the Netherlands), René van den Berg (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Albert Yoo (MD, PhD) (University Hospital, LMU Munich, Munich, Germany), Ludo Beenen (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Alida Postma (MD, PhD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Stefan Roosendaal (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Bas van der Kallen (MD, PhD) (Rijnstate Hospital, Arnhem, the Netherlands), Ido van den Wijngaard (MD, PhD) (Haaglanden Medical Center, the Hague, the Netherlands), Adriaan van Es (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Bart Emmer (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Jasper Martens (MD) (Rijnstate Hospital, Arnhem, the Netherlands), Lonneke Yo (MD, PhD) (Catharina Hospital, Eindhoven, the Netherlands), Jan Albert Vos (MD, PhD) (St. Antonius Hospital, Nieuwegein, the Netherlands), Joost Bot (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Pieter-Jan van Doormaal (MD, PhD) (University Medical Center Utrecht, Utrecht, the Netherlands), Anton Meijer (MD, PhD) (Radboud University Medical Center, Nijmegen, the Netherlands), Elyas Ghariq (MD) (Haaglanden Medical Center, the Hague, the Netherlands), Reinoud Bokkers (MD, PhD) (University Medical Center Groningen, Groningen, the Netherlands), Menno Krietemeijer (MD) (Catharina Hospital, Eindhoven, the Netherlands), Hieronymus Boogaarts (MD, PhD) (Radboud University Medical Center, Nijmegen, the Netherlands), Rob Lo (MD, PhD) (University Medical Center Utrecht, Utrecht, the Netherlands), Wouter Dinkelaar (MD) (Albert Schweitzer Hospital, Dordrecht, the Netherlands), Auke Appelman (MD, PhD) (University Medical Center Groningen, Groningen, the Netherlands), Bas Hammer (MD) (HagaZiekenhuis, the Hague, the Netherlands), Sjoert Pegge (MD) (HagaZiekenhuis, the Hague, the Netherlands), Anouk van der Hoorn (MD, PhD) (Rijnstate Hospital, Arnhem, the Netherlands), Saman Vinke (MD, PhD) (Radboud University Medical Center, Nijmegen, the Netherlands), Sandra Cornelissen (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Christiaan van der Leij (MD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Rutger Brans (MD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Jeanette Bakker (MD, PhD) (Albert Schweitzer Hospital, Dordrecht, the Netherlands), Maarten Uyttenboogaart (MD, PhD) (University Medical Center Groningen, Groningen, the Netherlands), Miou Koopman (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Lucas Smagge (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Olvert A. Berkhemer (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Jeroen Markenstein (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Eef Hendriks (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Patrick Brouwer (MD, PhD) (Leiden University Medical Center, Leiden, the Netherlands). Data management group: Bart Emmer (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Charles Majoie (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Henk van Voorst (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Arnolt-Jan Hoving (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands). CONTRAST imaging data management: Aad van der Lugt (MD, PhD) (University Medical Center Utrecht, Utrecht, the Netherlands), Charles Majoie (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Adriaan Versteeg (University Medical Center Utrecht, Utrecht, the Netherlands), Lennard Wolff (MD) (University Medical Center Utrecht, Utrecht, the Netherlands), Jiahang Su (MSc) (University Medical Center Utrecht, Utrecht, the Netherlands), Manon Tolhuisen (MSc) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Henk van Voorst (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands). MR CLEAN Registry clinical/imaging data acquisition: Esmee Venema (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Vicky Chalos (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Ralph Geuskens (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Tim van Straaten (Radboud University Medical Center, Nijmegen, the Netherlands), Saliha Ergezen (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Roger Harmsma (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Daan Muijres (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Anouk de Jong (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Olvert Berkhemer (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Merel Boers (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), J. Huguet (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Paul Groot (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Marieke Mens (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Katinka van Kranendonk (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Kilian Treurniet (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Manon Tolhuisen (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Heitor Alves (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Annick Weterings (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Eleonora Kirkels (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Eva Voogd (Rijnstate Hospital, Arnhem, the Netherlands), Lieve Schupp (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Sabine L. Collette (University Medical Center Groningen, Groningen, the Netherlands), Adrien Groot (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Natalie LeCouffe (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Praneeta Konduri (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Haryadi Prasetya (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Nerea Arrarte Terreros (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Lucas Ramos (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Nikki Boodt (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Anne Pirson (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Agnetha Bruggeman (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Nadinda van der Ende (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Rabia Deniz (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Susan Olthuis (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Floor Pinckaers (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands). CLEOPATRA local collaborators: Arnolt-Jan Hoving (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Henk van Voorst (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Daan Peerlings (MSc) (University Medical Center Utrecht, Utrecht, the Netherlands), Jasper Daems (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Agnetha Bruggeman (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Miou Koopman (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Anke Wouters (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Floor Pinckaers (MD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Susan Olthuis (MD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands). CONTRAST local collaborators: Josje Brouwer (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Manon Kappelhof (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Vicky Chalos (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Kilian Treurniet (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Sophie van den Berg (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Natalie LeCouffe (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Rob van de Graaf (MD) (University Medical Center Utrecht, Utrecht, the Netherlands), Robert-Jan Goldhoorn (MD, PhD) (Rijnstate Hospital, Arnhem, the Netherlands), Aladdin Taha (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Samantha Donse-Donkel (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Wouter Hinsenveld (MD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Anne Pirson (MD) (Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands), Lotte Sondag (MD) (Haaglanden Medical Center, the Hague, the Netherlands), Manon Kappelhof (MD, PhD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Rik Reinink (MD) (University Medical Center Groningen, Groningen, the Netherlands), Manon Tolhuisen (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Josje Brouwer (MD) (Amsterdam University Medical Centers, location University of Amsterdam, Amsterdam the Netherlands), Lennard Wolff (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Sabine Collette (University Medical Center Groningen, Groningen, the Netherlands), Wouter van der Steen (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands). MR CLEAN Registry: Executive committee: Diederik W.J. Dippel (Department of Neurology, Erasmus MC University Medical Center), Aad van der Lugt (Department of Radiology, Erasmus MC University Medical Center), Charles B.L.M. Majoie (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Yvo B.W.E.M. Roos (Department of Neurology, Amsterdam UMC, location University of Amsterdam), Robert J. van Oostenbrugge (Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Cardiovascular Diseases Maastricht (CARIM), Maastricht, the Netherlands), Wim H. van Zwam (Department of Radiology & Nuclear Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Cardiovascular Diseases Maastricht (CARIM), Maastricht, the Netherlands), Jelis Boiten (Department of Neurology, Haaglanden MC, the Hague), Jan Albert Vos (Department of Radiology, Sint Antonius Hospital, Nieuwegein). Study coordinators: Ivo G.H. Jansen (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Maxim J.H.L. Mulder (Department of Neurology, Erasmus MC University Medical Center; Department of Radiology, Erasmus MC University Medical Center), Robert- Jan B. Goldhoorn (Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of Radiology & Nuclear Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Cardiovascular Diseases Maastricht (CARIM), Maastricht, the Netherlands), Kars C.J. Compagne (Department of Radiology, Erasmus MC University Medical Center), Manon Kappelhof (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Josje Brouwer (Department of Neurology, Amsterdam UMC, location University of Amsterdam), Sanne J. den Hartog (Department of Neurology, Erasmus MC University Medical Center; Department of Radiology, Erasmus MC University Medical Center; Department of Public Health, Erasmus MC University Medical Center), Wouter H. Hinsenveld (Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of Radiology & Nuclear Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands), Lotte van den Heuvel (Department of Neurology, Erasmus MC University Medical Center; Department of Public Health, Erasmus MC University Medical Center). Local principal investigators: Diederik W.J. Dippel (Department of Neurology, Erasmus MC University Medical Center), Bob Roozenbeek (Department of Neurology, Erasmus MC University Medical Center), Aad van der Lugt (Department of Radiology, Erasmus MC University Medical Center), Pieter Jan van Doormaal (Department of Radiology, Erasmus MC University Medical Center), Charles B.L.M. Majoie (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Yvo B.W.E.M. Roos (Department of Neurology, Amsterdam UMC, location University of Amsterdam), Bart J. Emmer (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Jonathan M. Coutinho (Department of Neurology, Amsterdam UMC, location University of Amsterdam), Wouter J. Schonewille (Department of Neurology, Sint Antonius Hospital, Nieuwegein), Jan Albert Vos (Department of Radiology, Sint Antonius Hospital, Nieuwegein), Marieke J.H. Wermer (Department of Neurology, Leiden University Medical Center), Marianne A.A. van Walderveen (Department of Radiology, Leiden University Medical Center), Adriaan C.G.M. van Es (Department of Radiology, Leiden University Medical Center), Julie Staals (Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Cardiovascular Diseases Maastricht (CARIM), Maastricht, the Netherlands), Robert J. van Oostenbrugge (Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Cardiovascular Diseases Maastricht (CARIM), Maastricht, the Netherlands), Wim H. van Zwam (Department of Radiology & Nuclear Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Cardiovascular Diseases Maastricht (CARIM), Maastricht, the Netherlands), Jeannette Hofmeijer (Department of Neurology, Rijnstate Hospital, Arnhem), Jasper M. Martens (Department of Radiology, Rijnstate Hospital, Arnhem), Geert J. Lycklama à Nijeholt (Department of Radiology, Haaglanden MC, the Hague), Jelis Boiten (Department of Neurology, Haaglanden MC, the Hague), Sebastiaan F. de Bruijn (Department of Neurology, HAGA Hospital, the Hague), Lukas C. van Dijk (Department of Radiology, HAGA Hospital, the Hague), H. Bart van der Worp (Department of Neurology, University Medical Center Utrecht), Rob H. Lo (Department of Radiology, University Medical Center Utrecht), Ewoud J. van Dijk (Department of Neurology, Radboud University Medical Center, Nijmegen), Hieronymus D. Boogaarts (Department of Neurosurgery, Radboud University Medical Center, Nijmegen), J. de Vries (Department of Neurology, Isala Klinieken, Zwolle), Paul L.M. de Kort (Department of Neurology, Elisabeth-TweeSteden ziekenhuis, Tilburg), Julia van Tuijl (Department of Neurology, Elisabeth-TweeSteden ziekenhuis, Tilburg), Issam Boukrab (Department of Radiology, Elisabeth-TweeSteden ziekenhuis, Tilburg), Jo P. Peluso (Department of Radiology, Elisabeth-TweeSteden ziekenhuis, Tilburg), Puck Fransen (Department of Neurology, Isala Klinieken, Zwolle), Jan S.P. van den Berg (Department of Neurology, Isala Klinieken, Zwolle), Heleen M. den Hertog (Department of Neurology, Isala Klinieken, Zwolle), Boudewijn A.A.M. van Hasselt (Department of Radiology, Isala Klinieken, Zwolle), Leo A.M. Aerden (Department of Neurology, Reinier de Graaf Gasthuis, Delft), René J. Dallinga (Department of Radiology, Reinier de Graaf Gasthuis, Delft), Maarten Uyttenboogaart (Department of Neurology, University Medical Center Groningen), Omid Eschgi (Department of Radiology, University Medical Center Groningen), Reinoud P.H. Bokkers (Department of Radiology, University Medical Center Groningen), Tobien H.C.M.L. Schreuder (Department of Neurology, Zuyderland Medical Center, Heerlen), Roel J.J. Heijboer (Department of Radiology, Zuyderland Medical Center, Heerlen), Koos Keizer (Department of Neurology, Catharina Hospital, Eindhoven), Rob A.R. Gons (Department of Neurology, Catharina Hospital, Eindhoven), Lonneke S.F. Yo (Department of Radiology, Catharina Hospital, Eindhoven), Emiel J.C. Sturm (Department of Radiology, Medisch Spectrum Twente, Enschede; Deventer Hospital, Medisch Spectrum Twente, Enschede), Tomas Bulut (Department of Radiology, Medisch Spectrum Twente, Enschede), Paul J.A.M. Brouwers (Department of Neurology, Medisch Spectrum Twente, Enschede), Anouk D. Rozeman (Department of Neurology, Albert Schweitzer Hospital, Dordrecht), Otto Elgersma (Department of Radiology, Albert Schweitzer Hospital, Dordrecht), Michel J.M. Remmers (Department of Neurology, Amphia Hospital, Breda), Thijs E.A.M. de Jong (Department of Radiology, Amphia Hospital, Breda). Imaging assessment committee: Charles B.L.M. Majoie (chair) (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Wim H. van Zwam (Department of Radiology & Nuclear Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Cardiovascular Diseases Maastricht (CARIM), Maastricht, the Netherlands), Aad van der Lugt (Department of Radiology, Erasmus MC University Medical Center), Geert J. Lycklama à Nijeholt (Department of Radiology, Haaglanden MC, the Hague), Marianne A.A. van Walderveen (Department of Radiology, Leiden University Medical Center), Marieke E.S. Sprengers (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Sjoerd F.M. Jenniskens (Department of Radiology, Radboud University Medical Center, Nijmegen), René van den Berg (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Albert J. Yoo (Department of Radiology, Texas Stroke Institute, Texas, United States of America), Ludo F.M. Beenen (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Alida A. Postma (Department of Radiology & Nuclear Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands; MHeNs School for Mental Health and Neuroscience, Maastricht, the Netherlands), Stefan D. Roosendaal (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Bas F.W. van der Kallen (Department of Radiology, Haaglanden MC, the Hague), Ido R. van den Wijngaard (Department of Radiology, Haaglanden MC, the Hague), Adriaan C.G.M. van Es (Department of Radiology, Leiden University Medical Center), Bart J. Emmer (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Jasper M. Martens (Department of Radiology, Rijnstate Hospital, Arnhem), Lonneke S.F. Yo (Department of Radiology, Catharina Hospital, Eindhoven), Jan Albert Vos (Department of Radiology, Sint Antonius Hospital, Nieuwegein), Joost Bot (Department of Radiology, Amsterdam UMC, Vrije Universiteit van Amsterdam, Amsterdam), Pieter-Jan van Doormaal (Department of Radiology, Erasmus MC University Medical Center), Anton Meijer (Department of Radiology, Radboud University Medical Center, Nijmegen), Elyas Ghariq (Department of Radiology, Haaglanden MC, the Hague), Reinoud P.H. Bokkers (Department of Radiology, University Medical Center Groningen), Marc P. van Proosdij (Department of Radiology, Noordwest Ziekenhuisgroep, Alkmaar), G. Menno Krietemeijer (Department of Radiology, Catharina Hospital, Eindhoven), Jo P. Peluso (Department of Radiology, Elisabeth-TweeSteden ziekenhuis, Tilburg), Hieronymus D. Boogaarts (Departmentof Neurosurgery, Radboud University Medical Center, Nijmegen), Rob Lo (Department of Radiology, University Medical Center Utrecht), Wouter Dinkelaar (Department of Radiology, Albert Schweitzer Hospital, Dordrecht), Auke P.A. Appelman (Department of Radiology, University Medical Center Groningen), Bas Hammer (Department of Radiology, HAGA Hospital, the Hague), Sjoert Pegge (Department of Radiology, Radboud University Medical Center, Nijmegen), Anouk van der Hoorn (Department of Radiology, University Medical Center Groningen), Saman Vinke (Department of Neurosurgery, Radboud University Medical Center, Nijmegen), Sandra Cornelissen (Department of Radiology, Erasmus MC University Medical Center), Christiaan van der Leij (Department of Radiology & Nuclear Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands), Rutger Brans (Department of Radiology & Nuclear Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands), Jeanette Bakker (Department of Radiology, Albert Schweitzer Hospital, Dordrecht), Maarten Uyttenboogaart (Department of Neurology, University Medical Center Groningen), Miou Koopman (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Lucas Smagge (Department of Radiology, Erasmus MC University Medical Center), Olvert A. Berkhemer (Department of Neurology, Erasmus MC University Medical Center; Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam; Department of Radiology & Nuclear Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands), Jeroen Markenstein (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Eef Hendriks (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Patrick Brouwer (Department of Radiology, Leiden University Medical Center), Dick Gerrits (Department of Radiology, Medisch Spectrum Twente, Enschede). Writing committee: Diederik W.J. Dippel (chair) (Department of Neurology, Erasmus MC University Medical Center), Aad van der Lugt (Department of Radiology, Erasmus MC University Medical Center), Charles B.L.M. Majoie (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Yvo B.W.E.M. Roos (Department of Neurology, Amsterdam UMC, location University of Amsterdam), Robert J. van Oostenbrugge (Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Cardiovascular Diseases Maastricht (CARIM), Maastricht, the Netherlands), Wim H. van Zwam (Department of Radiology & Nuclear Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Cardiovascular Diseases Maastricht (CARIM), Maastricht, the Netherlands), Geert J. Lycklama à Nijeholt (Department of Radiology, Haaglanden MC, the Hague), Jelis Boiten (Department of Neurology, Haaglanden MC, the Hague), Jan Albert Vos (Department of Radiology, Sint Antonius Hospital, Nieuwegein), Wouter J. Schonewille (Department of Neurology, Sint Antonius Hospital, Nieuwegein), Jeannette Hofmeijer (Department of Neurology, Rijnstate Hospital, Arnhem), Jasper M. Martens (Department of Radiology, Rijnstate Hospital, Arnhem), H. Bart van der Worp (Department of Neurology, University Medical Center Utrecht), Rob H. Lo (Department of Radiology, University Medical Center Utrecht). Adverse event committee: Robert J. van Oostenbrugge (chair) (Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Cardiovascular Diseases Maastricht (CARIM), Maastricht, the Netherlands), Jeannette Hofmeijer (Department of Neurology, Rijnstate Hospital, Arnhem), H. Zwenneke Flach (Department of Radiology, Isala Klinieken, Zwolle). Trial methodologist: Hester F. Lingsma (Department of Public Health, Erasmus MC University Medical Center). Research nurses / local trial coordinators: Naziha el Ghannouti (Department of Neurology, Erasmus MC University Medical Center), Martin Sterrenberg (Department of Neurology, Erasmus MC University Medical Center), Wilma Pellikaan (Department of Neurology, Sint Antonius Hospital, Nieuwegein), Rita Sprengers (Department of Neurology, Amsterdam UMC, location University of Amsterdam), Marjan Elfrink (Department of Neurology, Rijnstate Hospital, Arnhem), Michelle Simons (Department of Neurology, Rijnstate Hospital, Arnhem), Marjolein Vossers (Department of Radiology, Rijnstate Hospital, Arnhem), Joke de Meris (Department of Neurology, Haaglanden MC, the Hague), Tamara Vermeulen (Department of Neurology, Haaglanden MC, the Hague), Annet Geerlings (Department of Neurology, Radboud University Medical Center, Nijmegen), Gina van Vemde (Department of Neurology, Isala Klinieken, Zwolle), Tiny Simons (Department of Neurology, Zuyderland Medical Center, Heerlen), Gert Messchendorp (Department of Neurology, University Medical Center Groningen), Nynke Nicolaij (Department of Neurology, University Medical Center Groningen), Hester Bongenaar (Department of Neurology, Catharina Hospital, Eindhoven), Karin Bodde (Department of Neurology, Reinier de Graaf Gasthuis, Delft), Sandra Kleijn (Department of Neurology, Medisch Spectrum Twente, Enschede), Jasmijn Lodico (Department of Neurology, Medisch Spectrum Twente, Enschede), Hanneke Droste (Department of Neurology, Medisch Spectrum Twente, Enschede), Maureen Wollaert (Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands), Sabrina Verheesen (Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands), D. Jeurrissen (Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands), Erna Bos (Department of Neurology, Leiden University Medical Center), Yvonne Drabbe (Department of Neurology, HAGA Hospital, the Hague), Michelle Sandiman (Department of Neurology, HAGA Hospital, the Hague), Nicoline Aaldering (Department of Neurology, Rijnstate Hospital, Arnhem), Berber Zweedijk (Department of Neurology, University Medical Center Utrecht), Jocova Vervoort (Department of Neurology, Elisabeth-TweeSteden ziekenhuis, Tilburg), Eva Ponjee (Department of Neurology, Isala Klinieken, Zwolle), Sharon Romviel (Department of Neurology, Radboud University Medical Center, Nijmegen), Karin Kanselaar (Department of Neurology, Radboud University Medical Center, Nijmegen), Denn Barning (Department of Radiology, Leiden University Medical Center), Laurine van der Steen (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam). Clinical/imaging data aquisition: Esmee Venema (Department of Public Health, Erasmus MC University Medical Center), Vicky Chalos (Department of Neurology, Erasmus MC University Medical Center; Department of Public Health, Erasmus MC University Medical Center), Ralph R. Geuskens (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Tim van Straaten (Department of Neurology, Radboud University Medical Center, Nijmegen), Saliha Ergezen (Department of Neurology, Erasmus MC University Medical Center), Roger R.M. Harmsma (Department of Neurology, Erasmus MC University Medical Center), Daan Muijres (Department of Neurology, Erasmus MC University Medical Center), Anouk de Jong (Department of Neurology, Erasmus MC University Medical Center), Olvert A. Berkhemer (Department of Neurology, Erasmus MC University Medical Center; Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam; Department of Radiology & Nuclear Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands), Anna M.M. Boers (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam; Department of Biomedical Engineering & Physics, Amsterdam UMC, location University of Amsterdam), J. Huguet (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), P.F.C. Groot (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Marieke A. Mens (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Katinka R. van Kranendonk (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Kilian M. Treurniet (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Manon L. Tolhuisen (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam; Department of Biomedical Engineering & Physics, Amsterdam UMC, location University of Amsterdam), Heitor Alves (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Annick J. Weterings (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Eleonora L.F. Kirkels (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Eva J.H.F. Voogd (Department of Neurology, Rijnstate Hospital, Arnhem), Lieve M. Schupp (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Sabine L. Collette (Department of Neurology, University Medical Center Groningen), (Department of Radiology, University Medical Center Groningen), Adrien E.D. Groot (Department of Neurology, Amsterdam UMC, location University of Amsterdam), Natalie E. LeCouffe (Department of Neurology, Amsterdam UMC, location University of Amsterdam), Praneeta R. Konduri (Department of Biomedical Engineering & Physics, Amsterdam UMC, location University of Amsterdam), Haryadi Prasetya (Department of Biomedical Engineering & Physics, Amsterdam UMC, location University of Amsterdam), Nerea Arrarte-Terreros (Department of Biomedical Engineering & Physics, Amsterdam UMC,location University of Amsterdam), Lucas A. Ramos (Department of Biomedical Engineering & Physics, Amsterdam UMC, location University of Amsterdam), Nikki Boodt (Department of Neurology, Erasmus MC University Medical Center; Department of Radiology, Erasmus MC University Medical Center; Department of Public Health, Erasmus MC University Medical Center), Anne F.A.V Pirson (Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands), Agnetha A.E. Bruggeman (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Nadinda A.M. van der Ende (Department of Neurology, Erasmus MC University Medical Center; Department of Radiology, Erasmus MC University Medical Center), Rabia Deniz (Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam), Susanne G.H. Olthuis (Department of Neurology, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Cardiovascular Diseases Maastricht (CARIM), Maastricht, the Netherlands), Floor Pinckaers (Department of Radiology & Nuclear Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands; School for Cardiovascular Diseases Maastricht (CARIM), Maastricht, the Netherlands). CONTRAST clinical trial collaborators: Research leaders: Diederik Dippel (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Charles Majoie (MD, PhD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands). Consortium coordinator: Rick van Nuland, (PhD) (Lygature, Utrecht, the Netherlands). Imaging assessment committee: Charles Majoie (MD, PhD) – Chair (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Aad van der Lugt (MD, PhD) – Chair (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Adriaan van Es (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands; Leiden University Medical Center, Leiden, the Netherlands), Pieter-Jan van Doormaal (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), René van den Berg (MD, PhD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Ludo Beenen (MD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Bart Emmer (MD, PhD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Stefan Roosendaal (MD, PhD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Wim van Zwam (MD, PhD) (Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands), Alida Annechien Postma (MD, PhD) (School for Mental Health and Sciences (Mhens), Maastricht University Medical Center, Maastricht, The Netherlands), Lonneke Yo (MD, PhD) (Catharina Hospital, Eindhoven, the Netherlands), Menno Krietemeijer (MD) (Catharina Hospital, Eindhoven, the Netherlands), Geert Lycklama (MD, PhD) (Haaglanden Medical Centre, the Hague, the Netherlands), Jasper Martens (MD) (Rijnstate Hospital, Arnhem, the Netherlands), Sebastiaan Hammer (MD, PhD) (Radboud University Medical Center, Nijmegen, the Netherlands), Anton Meijer (MD, PhD) (Radboud University Medical Center, Nijmegen, the Netherlands), Reinoud Bokkers (MD, PhD) (University Medical Center Groningen, Groningen, the Netherlands), Anouk van der Hoorn (MD, PhD) (University Medical Center Groningen, Groningen, the Netherlands), Ido van den Wijngaard (MD, PhD) (Leiden University Medical Center, Leiden, the Netherlands; Haaglanden Medical Centre, the Hague, the Netherlands), Albert Yoo (MD, PhD) (Texas Stroke Institute, Dallas-Fort Worth, Texas, United States of America), Dick Gerrits (MD) (Medisch Spectrum Twente, Enschede, The Netherlands). Adverse event committee: Robert van Oostenbrugge (MD, PhD) – Chair (Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands), Bart Emmer (MD, PhD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Jonathan M. Coutinho (MD, PhD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Martine Truijman (MD, PhD) (Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands), Julie Staals (MD, PHD) (Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands), Bart van der Worp (MD, PhD) (University Medical Center Utrecht, Brain Center Rudolf Magnus, Utrecht, the Netherlands), J. Boogaarts (MD, PhD) (Radboud University Medical Center, Nijmegen, the Netherlands), Ben Jansen (MD, PhD) (Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands), Sanne Zinkstok (MD, PhD) (TerGooi, Hilversum, The Netherlands). Outcome assessment committee: Yvo Roos (MD, PhD) – Chair (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Peter Koudstaal (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Diederik Dippel (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Jonathan M. Coutinho (MD, PhD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Koos Keizer (MD, PhD) (University Medical Center Utrecht, Brain Center Rudolf Magnus, Utrecht, the Netherlands), Sanne Manschot (MD, PhD) (Haaglanden Medical Centre, the Hague, the Netherlands), Jelis Boiten (MD, PhD) (Haaglanden Medical Centre, the Hague, the Netherlands), Henk Kerkhoff (MD, PhD) (Albert Schweitzer Hospital, Dordrecht, the Netherlands), Ido van den Wijngaard (MD, PhD) (Leiden University Medical Center, Leiden, the Netherlands; Haaglanden Medical Centre, the Hague, the Netherlands). Data management group: Hester Lingsma (PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Diederik Dippel (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Vicky Chalos (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Olvert Berkhemer (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands; Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands). Imaging data management: Aad van der Lugt (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Charles Majoie (MD, PhD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Adriaan Versteeg (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Lennard Wolff (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Matthijs van der Sluijs (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Henk van Voorst (MD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Manon Tolhuisen (Msc) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands). Biomaterials and translational group: Hugo ten Cate (MD, PhD) (Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands), Moniek de Maat (PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Samantha Donse-Donkel (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Heleen van Beusekom (PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Aladdin Taha (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Aarazo Barakzie (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands). Local collaborators: Vicky Chalos (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Rob van de Graaf (MD, PhD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Wouter van der Steen (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Aladdin Taha (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Samantha Donse-Donkel (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Lennard Wolff (MD) (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Kilian Treurniet (MD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Sophie van den Berg (MD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Natalie LeCouffe (MD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Manon Kappelhof (MD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Rik Reinink (MD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Manon Tolhuisen (MD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Leon Rinkel (MD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Josje Brouwer (MD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Agnetha Bruggeman (MD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Henk van Voorst (MD) (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Robert-Jan Goldhoorn (MD) (Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands), Wouter Hinsenveld (MD) (Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands), Anne Pirson (MD) (Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands), Susan Olthuis (MD) (Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands), Simone Uniken Venema (MD) (University Medical Center Utrecht, Brain Center Rudolf Magnus, Utrecht, the Netherlands), Sjan Teeselink (MD) (Radboud University Medical Center, Nijmegen, the Netherlands), Lotte Sondag (MD) (Radboud University Medical Center, Nijmegen, the Netherlands), Sabine Collette (MD) (University Medical Center Groningen, Groningen, the Netherlands). Research nurses: Martin Sterrenberg (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Naziha El Ghannouti (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Laurine van der Steen (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands), Sabrina Verheesen (Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands), Jeannique Vranken (Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands), Ayla van Ahee (University Medical Center Utrecht, Brain Center Rudolf Magnus, Utrecht, the Netherlands), Hester Bongenaar (Catharina Hospital, Eindhoven, the Netherlands), Maylee Smallegange (Catharina Hospital, Eindhoven, the Netherlands), Lida Tilet (Catharina Hospital, Eindhoven, the Netherlands), Joke de Meris (Haaglanden Medical Centre, the Hague, the Netherlands), Michelle Simons (Rijnstate Hospital, Arnhem, the Netherlands), Wilma Pellikaan (St. Antonius Hospital, Nieuwegein, the Netherlands), Wilma van Wijngaarden (St. Antonius Hospital, Nieuwegein, the Netherlands), Kitty Blauwendraat (St. Antonius Hospital, Nieuwegein, the Netherlands), Yvonne Drabbe (HagaZiekenhuis, the Hague, the Netherlands), Michelle Sandiman-Lefeber (HagaZiekenhuis, the Hague, the Netherlands), Anke Katthöfer (HagaZiekenhuis, the Hague, the Netherlands), Eva Ponjee (Isala, Zwolle, the Netherlands), Rieke Eilander (Isala, Zwolle, the Netherlands), Anja van Loon (Amphia Hospital, Breda, the Netherlands), Karin Kraus (Amphia Hospital, Breda, the Netherlands), Suze Kooij (Albert Schweitzer Hospital, Dordrecht, the Netherlands), Annemarie Slotboom (Albert Schweitzer Hospital, Dordrecht, the Netherlands), Marieke de Jong (University Medical Center Groningen, Groningen, the Netherlands), Friedus van der Minne (University Medical Center Groningen, Groningen, the Netherlands), Esther Santegoets (Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands), Rita Sprengers (Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands). Study monitors: Leontien Heiligers (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Yvonne Martens (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Naziha El Ghannouti (Erasmus MC University Medical Center, Rotterdam, the Netherlands).

          • Contributors HvV: Lead author, conceptual design, conducted research and statistical analysis, initial writing manuscript. JWH: Data collection and processing, conceptual design, initial writing of manuscript and revisions. MSK: Data collection and processing, conceptual design, revision of manuscript. JDD: Data collection and processing, revision of manuscript. DP: Data collection and processing, conceptual design, revision of manuscript. EB: Co-lead statistician and health economist, conceptual design, revision of manuscript, funding of project. HL: Co-lead statistician and health economist, conceptual design, revision of manuscript, funding of project. HAM: Conceptual design (technical imaging analysis), revision of manuscript, funding of project. HWAMdJ: Conceptual design (technical imaging analysis), revision of manuscript, funding of project. OAB: Revision of manuscript, data collection and processing, project administration. WHvZ: Conceptual design, revision of manuscript, project administration, data collection. MAAvW: Revision of manuscript, data collection. IRvdW: Revision of manuscript, data collection. DWJD: Revision of manuscript, data collection, project administration, funding of project, conceptual design. AJY: Revision of manuscript, data collection, conceptual design. BC: Revision of manuscript, conceptual design. WGK: Revision of manuscript, analytical model development, conceptual design. CBM: conceptual design, revision of manuscript, project administration, data collection, funding of project. BJE: conceptual design, revision of manuscript, lead project administration, data collection, funding of project. BJE is the guarantor.

          • Funding The CLEOPATRA healthcare evaluation study was funded by Leading the Change (LtC). LtC is financed by Zorgverzekeraars Nederland (ZN) and supports various healthcare evaluations in the Netherlands as part of the ‘Healthcare Evaluation Netherlands’ project. LtC was not involved in the study design, monitoring, data collection, statistical analyses, interpretation of results or manuscript writing, but the progress of the study was continuously monitored by LtC. The MR CLEAN-NO IV trial (ISRCTN80619088) and MR CLEAN-MED trial (ISRCTN76741621) were part of the Collaboration for New Treatments of Acute Stroke (CONTRAST) consortium. The CONTRAST consortium acknowledges the support from the Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation (CVON2015-01: CONTRAST), and from the Brain Foundation Netherlands (HA2015.01.06). The collaboration project is additionally financed by the Ministry of Economic Affairs by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public–private partnerships (LSHM17016). This work was funded in part through unrestricted funding by Stryker, Medtronic and Cerenovus. The funding sources were not involved in study design, monitoring, data collection, statistical analyses, interpretation of results or manuscript writing.

          • Competing interests BJE reports grants from LtC (ZonMW and TKI-PPP of Health Holland). WHvZ reports speaker fees from Cerenovus, NicoLab and Stryker, and consulting fees from Philips, all paid to Institution. DWJD report grants from the Dutch Heart Foundation, Brain Foundation Netherlands, ZON MW, Stryker, Medtronic, Cerenovus, Thrombolytic Science, received by the Erasmus University Medical Center outside this project. AJY reports Research grants from Medtronic, Cerenovus, Penumbra, Stryker, and Genentech. Consultant for Penumbra, Cerenovus, Nicolab, Philips, Vesalio, Zoll Circulation, and NIH/NINDS. CBM: grants from Healthcare Evaluation Netherlands, CVON/Dutch Heart Foundation, TWIN foundation and Stryker during the conduct of the study and from European Commission outside this project (all paid to institution) and is shareholder of Nicolab. All other contributors report no other conflicts of interest.

          • Provenance and peer review Not commissioned; externally peer reviewed.

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