Gatifloxacin Versus Ceftriaxone in the Treatment of Enteric Fever

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

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.

Study Overview

• Status: Completed
• Conditions: Typhoid Fever; Enteric Fever
• Intervention / Treatment: Drug: Gatifloxacin; Drug: Ceftriaxone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 4

Contacts and Locations

Study Locations

• Nepal
  • Kathmandu, Nepal
    • Civil Hospital
  • Kathmandu, Nepal
    • Patan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Gatifloxacin; Gatifloxacin 10mg/kg/day for 7 days	Drug: Gatifloxacin; Gatifloxacin 10 mg/kg/day for 7 days. Tablets for oral administration.
Active Comparator: Ceftriaxone; ≥2-<14 years - 60mg/kg/ once daily for 7 days; 14 years and older - 2g once daily for 7 days	Drug: Ceftriaxone; ≥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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Oxford University Clinical Research Unit, Vietnam
• Collaborators: University of Oxford; Patan Academy of Health Sciences, Nepal; Patan Hospital, Nepal; Civil Hospital, Nepal
• Investigators: Principal Investigator: Buddha Basnyat, MD, University of Oxford

Publications and helpful links

General Publications

• Arjyal A, Basnyat B, Nhan HT, Koirala S, Giri A, Joshi N, Shakya M, Pathak KR, Mahat SP, Prajapati SP, Adhikari N, Thapa R, Merson L, Gajurel D, Lamsal K, Lamsal D, Yadav BK, Shah G, Shrestha P, Dongol S, Karkey A, Thompson CN, Thieu NTV, Thanh DP, Baker S, Thwaites GE, Wolbers M, Dolecek C. Gatifloxacin versus ceftriaxone for uncomplicated enteric fever in Nepal: an open-label, two-centre, randomised controlled trial. Lancet Infect Dis. 2016 May;16(5):535-545. doi: 10.1016/S1473-3099(15)00530-7. Epub 2016 Jan 20.

Helpful Links

• Oxford University Clinical Research Unit, Viet Nam
• Oxford University Clinical Research Unit, Nepal
• Trial Ethical Approval letters and Informed Consent Forms

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: August 22, 2011
• First Submitted That Met QC Criteria: August 22, 2011
• First Posted (Estimate): August 23, 2011

Study Record Updates

• Last Update Posted (Estimate): October 4, 2016
• Last Update Submitted That Met QC Criteria: October 2, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Ceftriaxone; Typhoid fever; Enteric fever; Gatifloxacin
• Additional Relevant MeSH Terms: Infections; Wounds and Injuries; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Body Temperature Changes; Heat Stress Disorders; Enterobacteriaceae Infections; Salmonella Infections; Hyperthermia; Fever; Typhoid Fever; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Pharmaceutical Solutions; Ophthalmic Solutions; Ceftriaxone; Gatifloxacin
• Other Study ID Numbers: 03NP