Gatifloxacin Versus Ceftriaxone in the Treatment of Enteric Fever

• ClinicalTrials.gov Identifier: NCT01421693
• Recruitment Status: Completed
• First Posted: August 23, 2011
• Last Update Posted: October 4, 2016
• Sponsor: Oxford University Clinical Research Unit, Vietnam
• Collaborators: University of Oxford; Patan Academy of Health Sciences, Nepal; Patan Hospital, Nepal; Civil Hospital, Nepal
• Information provided by (Responsible Party): Oxford University Clinical Research Unit, Vietnam

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Enteric Fever; Typhoid Fever	Drug: Ceftriaxone; Drug: Gatifloxacin	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, Open-label, Superiority Trial of the Effectiveness of Gatifloxacin Versus Ceftriaxone for the Treatment of Uncomplicated Enteric Fever.
• Study Start Date: September 2011
• Actual Primary Completion Date: July 2014
• Actual Study Completion Date: January 2015

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Rate of treatment failure [ Time Frame: upon occurance, within 28 days ]

   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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Nepal

Civil Hospital

Kathmandu, Nepal

Patan Hospital

Kathmandu, Nepal

Sponsors and Collaborators

Oxford University Clinical Research Unit, Vietnam

University of Oxford

Patan Academy of Health Sciences, Nepal

Patan Hospital, Nepal

Civil Hospital, Nepal

Investigators

• Principal Investigator: Buddha Basnyat, MD; University of Oxford

More Information

Additional Information:

Oxford University Clinical Research Unit, Viet Nam 

Oxford University Clinical Research Unit, Nepal 

Trial Ethical Approval letters and Informed Consent Forms 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Oxford University Clinical Research Unit, Vietnam
• ClinicalTrials.gov Identifier: NCT01421693
• Other Study ID Numbers: 03NP
• First Posted: August 23, 2011
• Last Update Posted: October 4, 2016
• Last Verified: October 2016

Keywords provided by Oxford University Clinical Research Unit, Vietnam:

Gatifloxacin; Ceftriaxone; Enteric fever; Typhoid fever

Additional relevant MeSH terms:

Typhoid Fever; Fever; Hyperthermia; Body Temperature Changes; Heat Stress Disorders; Wounds and Injuries; Salmonella Infections; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Ceftriaxone; Gatifloxacin; Anti-Bacterial Agents; Anti-Infective Agents; Ophthalmic Solutions; Pharmaceutical Solutions; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents