Protocol for Thesis Faculty of Medical Sciences University of Delhi Dr XYZ Postgraduate student Department of ABCD University College of Medical Sciences & GTB Hospital

Supervisor:Dr. A Professor Dept. of ABCD UCMS & GTB Hospital Delhi Co-Supervisors:Dr. B Professor Dept. of EFGH UCMS & GTB Hospital Delhi Dr. C Professor & Head Dept. of IJKL UCMS & GTB Hospital Delhi

Title Single Dose Azithromycin versus Ciprofloxacin for Cholera in Children: A Randomized Controlled Trial

Background Cholera: significant health concern Ciprofloxacin: effective Flouroquinolone resistance: hence alternatives required Oral single-dose azithromycin: good results in adults Children: no similar studies

Aim Treatment efficacy of single dose Azithromycin versus Ciprofloxacin in children with cholera

Objectives 1.To compare clinical success of single dose treatment with Azithromycin and with Ciprofloxacin in children with cholera 2.To compare bacteriological success of single dose treatment with Azithromycin and with Ciprofloxacin in children with cholera

Setting: Departments of ABCD and EFGH, University College of Medical Sciences and GTB Hospital, Delhi. Study Design: Randomized, open labeled, clinical controlled trial. Study Period: November 2017-March 2019 Consent and Ethics: Written informed consent and Institutional Ethical Clearance

Participants Inclusion criteria Children (2-12 years) with (all three) Acute watery diarrhea (≤24 h) Severe dehydration, Positive for V. cholerae by HD examination or stool culture Exclusion criteria Severe under-nutrition Co-existing systemic illness Blood in stool Receiving antibiotic/antidiarrheal within preceding 24 h

Sample size Equivalence study At least 87 patients (each group) to ensure difference in clinical success rate between groups should not exceed 10% Power= 80% α error= 5% β error= 20% * Khan WA, et al. Randomised controlled comparison of single-dose ciprofloxacin and doxycycline for cholera caused by Vibrio cholerae 01 or Lancet. 1996;348(9023):

Methods Randomization: Simple Allocation: sealed envelope technique Intervention: Immediate rehydration (WHO Guidelines) followed by  Oral azithromycin {20 mg/kg, dispersible tab} single dose  Oral ciprofloxacin {20mg/kg dispersible tab} single dose Monitoring: 8 hourly (from drug delivery) Time of discharge: 72 hours (day 3) or until resolution of watery diarrhea, whichever is later. Follow-up visit: day 7

Bacteriological procedures Stool collection: Fresh stool / rectal swab Hanging drop examination Transport : Alkaline peptone water/ Cary Blair media. Stool culture: Bile salt agar, Mac Conkey agar and thiosulphate citrate bile sucrose agar. Incubation: 37ºC for 24 hours Enrichment: alkaline peptone water Serotyping: Slide agglutination test Antimicrobial susceptibility testing: Kirby-Bauer disc diffusion techinque

Outcome measures Primary Clinical success (resolution of diarrhea within 72 hrs ) Bacteriological success (cessation of Vibrio cholerae excretion by day 3) Secondary Recovery Time: total duration of diarrhea Total requirement of ORS/ intravenous therapy Proportion of children with clinical or bacteriological relapse

Statistical analysis Chi-square/Fisher’s exact test: to compare frequency of – Clinical and Bacteriological success – Clinical or bacteriological relapse Unpaired t-test: to compare – Duration of diarrhea & excretion of Vibrio – requirement of RL and ORS P<0.05 Repeated measure ANOVA: for variables like mean frequency of stool (Days 1, 2, 3 and 7) and level of significance to allow multiple comparisons

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