Single Dose Ciprofloxacin in the Treatment of Childhood Cholera:Randomized Controlled Clinical Trial
Information source: International Centre for Diarrhoeal Disease Research, Bangladesh
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Condition(s) targeted: Cholera
Intervention: Ciprofloxacin (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: International Centre for Diarrhoeal Disease Research, Bangladesh Official(s) and/or principal investigator(s): Debasish Saha, MBBS,MS, Study Director, Affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
Summary
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.
Clinical Details
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.
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Rates of clinical success
Secondary outcome: 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. Safety. PK-assessment of serum and stool.
Detailed description:
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.
Eligibility
Minimum age: 2 Years.
Maximum age: 15 Years.
Gender(s): Male.
Criteria:
Inclusion Criteria:
Age: 2-15 years. Gender: male. Duration of illness: <24 hours. Written informed consent
for participation in the study from either of the parents, or guardian, and oral assent
from children aged ³ 8 years.
Severe dehydration according to World Health Organisation (WHO) guidelines. Positive stool
dark field microscopic examination for V. cholerae.
Exclusion Criteria:
History of receiving any antimicrobial agent (including study drugs) effective in the
treatment of V. cholerae within 72 hours of screening.
Concomitant infection(s) requiring antimicrobial therapy. A concomitant illness that may
interfere with the evaluation of outcome or safety of the study drugs.
Patients with known chronic renal insufficiency. [As all cholera patients with moderate
to severe dehydration have pre-renal insufficiency on admission, and as it is not possible
to detect whether a patient has renal failure until the patient has been hydrated for at
least 24 hours, serum creatinine will be checked 24 hours post-administration of first
dose of study medication, on Day 5, and at any time as clinically indicated. (If the
baseline creatinine is > 200 mcmol/L, any patient with creatinine > than 200 mcmol/L 24
hours post-administration, will be considered as suffering from renal failure and will be
withdrawn from the trial.) Patients with known cardiac or hepatic impairment, i. e.
SGOT/SGPT or bilirubin > 3 times the upper limit of normal, and patients with a history of
central nervous system (CNS) disorders (known risk of experiencing seizures, a history of
convulsive disorders or head injury trauma, currently on anti-seizure medication or within
two months post-stroke).
Patients previously enrolled in the study. Patients participating in any clinical study
within one month prior to study entry.
Patients’ known to have AIDS. Patients treated with quinolones in the 14 days prior to the
study. Patients known to have underlying rheumatological disease, joint problems, etc.
Patients with a known hypersensitivity to any of the study drug regimens or related
compounds (including fluoroquinolones and macrolides).
Female patients who are lactating, or are sexually active and using unreliable
contraception.
Patients having a known underlying rheumatological disease, joint problems secondary to
trauma or pre-existing conditions known to be associated with arthropathy.
Patients with conditions precluding the performance of a reliable series of
musculoskeletal examinations are to be excluded from trial participation.
Locations and Contacts
International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka 1212, Bangladesh
Additional Information
Starting date: May 2001
Last updated: November 18, 2005
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