Single Dose Ciprofloxacin in the Treatment of Childhood Cholera:Randomized Controlled Clinical Trial

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Brief Title

Single Dose Ciprofloxacin in the Treatment of Childhood Cholera:Randomized Controlled Clinical Trial

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.

Brief 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.
    

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.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Rates of clinical success

Secondary Outcome

 Rates of bacteriologic success at test of cure visit.

Condition

Cholera

Intervention

Ciprofloxacin


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

180

Start Date

May 2001

Completion Date

July 2002


Eligibility 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.
      

Gender

Male

Ages

2 Years - 15 Years

Accepts Healthy Volunteers

No

Contacts

Debasish Saha, MBBS,MS, , 

Location Countries

Bangladesh

Location Countries

Bangladesh

Administrative Informations


NCT ID

NCT00142272

Organization ID

2000-032_



Study Sponsor

International Centre for Diarrhoeal Disease Research, Bangladesh

Collaborators

 Bayer

Study Sponsor

Debasish Saha, MBBS,MS, Study Director, International Centre for Diarrhoeal Disease Research, Bangladesh


Verification Date

September 2005