Single Dose Ciprofloxacin in the Treatment of Childhood Cholera:Randomized Controlled Clinical Trial
The study will be conducted to compare the efficacy and safety of a single dose of ciprofloxacin oral suspension 20 mg/kg with a 3-day course of erythromycin oral suspension administered in a dose of 12.5 mg/kg every 6 hours (12 doses) in the treatment of children, aged 2-15 years with clinically severe cholera due to V. cholerae O1 or O139.
We hypothesize that single dose ciprofloxacin would result in similar outcome in the clinicalcurewith that of erythromycin given in multiple doses.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomised, Open, Parallel Group Clinical Trial to Compare the Efficacy and Safety of a Single Dose of Ciprofloxacin Oral Suspension 20 Mg/Kg With a 3-Day Course of Erythromycin Oral Suspension Administered in a Dose of 12.5 Mg/Kg Every 6 Hours (12 Doses) in the Treatment of Children,With Clinically Severe Cholera Due to V. Cholerae O1 or O139.|
- Rates of clinical success
- Rates of bacteriologic success at test of cure visit.
- Duration of diarrhoea.
- Rates of clinical relapse.
- Rates of bacteriologic relapse.
- Duration of faecal excretion of V. cholerae O1 or V. cholerae O139.
- Measurements of six-hourly volume of watery stool will be done for the period in which patients are hospitalised.
- Proportion of patients requiring unscheduled intravenous fluids.
- Frequency of vomiting and its volume.
- Frequency of stool per day.
- Frequency of vomit per day.
- PK-assessment of serum and stool.
|Study Start Date:||May 2001|
|Estimated Study Completion Date:||July 2002|
Eligible patients will be admitted to the Clinical Study Ward of the Dhaka and Matlab Hospitals of ICDDR,B. Upon admission, their weight (dehydrated weight) and vital signs will be recorded, and a thorough physical examination, including assessment of dehydration (following WHO guidelines), will be made. Patients will then be rehydrated using intravenous Dhaka Solution (133, 13, 98 and 48 mmol/l of sodium, potassium, chloride and bicarbonate, respectively) over 3-4 hours. Thereafter, they will be observed over a 4-hour Observation Period when their hydration will be maintained using the rice-based oral rehydration solution (ORS) (containing 3.5, 2.5, 1.5 and 50 gram/l of sodium chloride, sodium bicarbonate, potassium chloride and rice powder). Dhaka Solution, as used for initial rehydration, will be used for patients whose hydration cannot be maintained by rice-based ORS.Patients who have a stool output of 20 ml/kg or more during the Observation Period, and who have V. cholerae demonstrated in dark-field microscopic examination of their freshly passed stool sample, will be enrolled upon obtaining written informed consent of their parents or guardians. If possible, assent must be obtained from the child. Patients will then be randomly assigned to receive one of the two treatment regimens. Children will be hospitalised for 5 days, from the initiation of study drug or until resolution of their diarrhoea, whichever will be longer, and they will be asked to return for a follow-up evaluation 10 to 14 days after study entry. Patients are to return for a further follow-up visit at 4 to 6 weeks (Day 28 to Day 42).Patients who develop joint changes during therapy, or during the follow-up period, must be followed up. Any new objective finding noted on clinical joint or gait assessment will be thoroughly evaluated by the investigator. This evaluation may include diagnostic procedures, such as MRI and/or joint fluid assessments, as appropriate. Patients with joint changes during therapy, or during the follow-up period, should be followed up until:a) The adverse event has been resolved orb) Until further change in the patient’s condition is unlikely and a final causality assessment has been made. This may be shorter or longer than 3 months from the time of discharge.Medical history will be obtained and a thorough physical examination will be performed daily. Vital signs and intake/output records will be maintained as from the initiation of rehydration.Patients will be closely monitored through bacteriological and laboratory assessments. Blood, urine and stool specimens will be taken at various time points. Stool culture for enteric pathogens will be done before initiation of the study drug, on study Day 3 and at follow-up visits. Rectal swab culture for V. cholerae will be done on each day of the study during the hospitalisation period, and at follow-up (10 to 14 days and 4 to 6 weeks). Complete blood count, serum electrolytes and creatinine, total bilirubin, SGPT and alkaline phosphatase will be determined before initiation of study drug and on study Day 5. (If the baseline creatinine is > 200 mcmol/L, creatinine will also be determined 24 hours post-administration of first dose of study medication, and any patient with a creatinine > than 200 mcmol/L will be considered as suffering from renal failure and will be withdrawn from the trial.) If possible, urinalysis will be done before initiation of drug therapy and on Day 5 of the study. Serum concentration of ciprofloxacin will be determined on the first day of the study at various time intervals after the first dose of the study drug.
|International Centre for Diarrhoeal Disease Research, Bangladesh|
|Dhaka, Bangladesh, 1212|
|Study Director:||Debasish Saha, MBBS,MS||International Centre for Diarrhoeal Disease Research, Bangladesh|