Gatifloxacin Versus Ceftriaxone in the Treatment of Enteric Fever

Study Overview
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Brief Summary
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The investigators aim to compare two antibiotic treatments for enteric (typhoid) fever. Three hundred patients at Patan Hospital will be enrolled in the study. Patients will be assigned to one of the two treatments by chance and followed for 6 months. The two treatment groups will be compared to see which treatment is more likely to make the patient better.

Detailed Description
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With the study hypothesis that Gatifloxacin is superior to Ceftriaxone in terms of treatment failure in patients with enteric fever, a comparative study will be conducted at Patan Hospital. 300 patients who are diagnosed with enteric fever will be enrolled into the study. The patients will be randomized to one of two groups. One group will receive treatment with Gatifloxacin for 7 days, and the other with Ceftriaxone. The patients will be followed during the treatment courses and at several points of 6 months after initial presentation. The endpoints then will be compared between two groups.

Official Title
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Randomized, Open-label, Superiority Trial of the Effectiveness of Gatifloxacin Versus Ceftriaxone for the Treatment of Uncomplicated Enteric Fever.

Conditions
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Enteric Fever, Typhoid Fever

Intervention / Treatment
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* Drug: Ceftriaxone
* Drug: Gatifloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Suspected or culture proven enteric fever >= 2 <= 45 years of age Fever >= 38°C for >= 4 days Informed consent to participate in the study Exclusion Criteria: Pregnancy Obtundation Shock Visible jaundice Presence of signs of gastrointestinal bleeding Evidence of severe disease Diabetes History of hypersensitivity to either of the trial drugs Known previous treatment with a quinolone antibiotic or 3rd generation cephalosporin or macrolide within one week of hospital admission.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gatifloxacin<br>Gatifloxacin 10mg/kg/day for 7 days | Drug: Gatifloxacin<br>* Gatifloxacin 10 mg/kg/day for 7 days. Tablets for oral administration.<br>|
| Active Comparator: Ceftriaxone<br>≥2-<14 years - 60mg/kg/ once daily for 7 days 14 years and older - 2g once daily for 7 days | Drug: Ceftriaxone<br>* ≥2-<14 years - 60mg/kg/ once daily for 7 days 14 years and older - 2g once daily for 7 days Intravenous infusion. Vials of crystalline powder.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of treatment failure | Any one (1) of the following defines treatment failure: Fever clearance time >7 x 24hours post treatment initiation Blood culture positive at Day 8 of treatment (microbiological failure) Requirement of rescue treatment Culture confirmed or syndromic relapse within 28 days of initiation of treatment The development on treatment of any enteric fever related complication within 28 days of initiation of treatment including, clinically significant bleeding, fall in the Glasgow Coma Score, perforation of the gastrointestinal tract or admission to hospital Both the absolute risk of treatment failure and the time to treatment failure will be analyzed | upon occurance, within 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| S.typhi or S.paratyphi carriage | Stool culture positive for S.typhi or S.paratyphi carriage | 1 month, 3 months and 6 months | 
| Number of adverse events | Treatment tolerance as defined by the number of adverse events, serious adverse events and disease complications | within 6 months | 
| Household transmission | Total number of febrile episodes, hospital visits and hospital admissions within household members | within 6 months | 
| Time to fever clearance | Time from first dose of treatment until a temperature which is ≤37•5°C for a 48 hour period is first recorded. | upon occurance, within 7 days | 
| Rate of culture-positive and syndromic clinical relapses |  | within 28 days of starting therapy | 
| Rate of relapses confirmed using additional diagnostic techniques | Additional techniques will include culture-PCR and gene expression profiling. | within 28 days of starting therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gatifloxacin, Ceftriaxone, Enteric fever, Typhoid fever