Treatment of mites folliculitis with an ornidazole-based sequential therapy

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Grouping and randomization method
The patients were blind to their treatment drugs and measures were taken to ensure that such a single-blind would not lead to assessment bias. Randomization was then performed by assigning the random numbers from random number tables to the two treatments. This strategy prevents the selection bias and insures against the accidental bias. To achieve allocation concealment, the staff members that involved in assigning random numbers to patients were excluded from selecting numbers.

Treatment
The enrolled patients were randomly assigned to two study groups (n=100 each). One group (79 female, 21 male) received ornidazole (0.5 g/time, t.d., per os) while the other group (72 female, 28 male) received metronidazole (0.2 g/time, q.d.s., per os) for 14 days. After four days of treatment, 50 patients in each group were randomly assigned to receive a single dose of CBI (1 mL, i.m.). The remaining 50 patients in each group were treated with ebastine (10 mg, o.d., per os) for 3 weeks. Topical rbFGF gel was applied to the lesions (1 g, t.d.) for 14 consecutive days beginning on day 7 post-ornidazole or -metronidazole treatment. Following rbFGF gel treatment, patients in the group treated with CBI received no further therapy, while patients in the group treated with ebastine continued antihistamine for one additional week. After completing respective treatments, the subjects in both groups were followed-up during clinical visits at 2, 4, 8, and 12 weeks post-treatment.

Content
The study protocol was approved by the Ethics Committee of Lanzhou General Hospital of Lanzhou Military Region, and a signed Informed Consent form was obtained from each patient prior to enrollment.

End points
The following surrogate endpoints for patients were set and patients will not be enrolled or advised to quit in each of the following situation: 1) not fulfill the inclusion criteria; 2) significant risk of safety issue; 3) no significant improvement of health; 3) don't follow the guidance; 4) no strict compliance of treatment strategy.

Clinical observation
Remission of facial skin lesions; mite numbers.

Biopsy of skin tissues for histopathological examination with consent
Statistical and effective rate analysis plan

Patients
The enrolled patients were randomly assigned to two study groups (n=100 each). One group (79 female, 21 male) received ornidazole (0.5 g/time, t.d., per os) while the other group (72 female, 28 male) received metronidazole (0.2 g/time, q.d.s., per os) for 14 days. After four days of treatment, 50 patients in each group were randomly assigned to receive a single dose of CBI (1 mL, i.m.). The remaining 50 patients in each group were treated with ebastine (10 mg, o.d., per os) for 3 weeks. Topical rbFGF gel was applied to the lesions (1 g, t.d.) for 14 consecutive days beginning on day 7 post-ornidazole or -metronidazole treatment. Following rbFGF gel treatment, patients in the group treated with CBI received no further therapy, while patients in the group treated with ebastine continued antihistamine for one additional week. After completing respective treatments, the subjects in both groups were followed-up during clinical visits at 2, 4, 8, and 12 weeks post-treatment.

Effective rate analysis
All the effective effect analysis will be based on an intention-to-treat population or per-protocol population method.

Adverse reactions and Relapse analysis
In case of severe adverse reactions with either treatment, the patient will be advised to quit the research and subjected to corresponding remedies accordingly.

Statistical method
All data were analyzed using IBM SPSS Statistics for Windows, Version 19.0. (Armonk, NY: IBM Corp).
Efficacy was defined as a remission of existing skin lesions and the absence of any new lesions. Chi-square test was used to compare the efficacies ornidazole and metronidazole after two weeks of treatment. Differences in the efficacies of ornidazole-and metronidazole-based regimens for preventing recurrence of Demodex mite infestations and formation of new lesions after an initial treatment were compared using survival analysis.
P-values < 0.05 were considered statistically significant.

Software and data presentation
The IBM SPSS Statistics for Windows, Version 19.0. (Armonk, NY: IBM Corp) will be used for statistical analysis, and data will be presented as mean ± standard deviation (SD) or percentage where appropriate.  Estimation of sample size is based on the minimum number of cases used in previous clinical trials using metronidazole therapy that the expected error value would be 10%. The level of significance was set as P=0.5 and confidence interval set 95% in the study. Thus, we would need to complete approximately 96 patients each group for the study. A brief outline of the study design is shown in Fig. 1