An open randomised comparison of gatifloxacin versus ofloxacin for the treatment of uncomplicated enteric fever

ISRCTN ISRCTN63006567
DOI https://doi.org/10.1186/ISRCTN63006567
Protocol serial number ctu01tyjan08
Sponsor University of Oxford (UK)
Funder The Wellcome Trust (UK) (grant ref: 077078)
Submission date
16/07/2008
Registration date
17/07/2008
Last edited
29/11/2013
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Christiane Dolececk
Scientific

The Oxford University Clinical Research Unit (OUCRU)
Hospital for Tropical Diseases
190 Ben Ham Tu
Ho Chi Minh City
Q5
Viet Nam

+84 8 924 1983
cdolececk@oucru.org

Study information

Primary study designInterventional
Study designAn open randomised two-way comparison trial
Secondary study designRandomised controlled trial
Study type Participant information sheet
Scientific title
Study objectivesWe hypothesise that gatifloxacin is more effective than ofloxacin in the treatment of enteric fever.
Ethics approval(s)Ethics approval received from:
1. Oxford Tropical Medicine Research Ethics Committee (OXTREC) (UK) on the 20th June 2006 (ref: 23/08)
2. Nepalese Local Ethics Committee on the 24th June 2008
Health condition(s) or problem(s) studiedEnteric fever (typhoid and paratyphoid fever)
InterventionGatifloxacin (10 mg/kg/day) once daily oral dose for 7 days versus ofloxacin (20 mg/kg/) twice daily oral dose for 7 days.

1. Prior to admission to the study:
1.1. Full history and clinical examination. In particular the following data will be documented: clinical manifestations according to a standard case record form (CRF).
1.2. Chest X-ray and other radiological investigations, including abdominal ultrasound, as clinically indicated

2. On admission to the study:
2.1. Name and address of the patient will be recorded on a detachable cover sheet of the CRF, (for mapping purposes)
2.2. Full blood counts including white cell differential, biochemistry (serum glutamic oxaloacetic transaminase [SGOT], serum glutamic pyruvic transaminase [SGPT], creatinine, glucose)
2.3. Blood for on-going host genetic studies of enteric fever from the patient
2.4. Microbiology:
2.4.1. Blood cultures (5 - 8 ml of blood)
2.4.2. Stool culture pre-treatment
2.5. Blood for typhoid diagnostic study (2 ml ethylenediaminetetraacetic acid [EDTA] blood)

3. Day 1 - Discharge:
Patients will be managed as outpatients and seen at home every day to day 10 or longer (until the patient gets better). The Nurse/Dr/Paramedic will visit the patient twice per day (at 12 hourly intervals) for 10 days or longer (until the patient gets better).
3.1. Treatment will be given under directly observed therapy
3.2. GPS mapping of patient's house
3.3. Axillary temperature will be recorded at 12 hourly intervals
3.4. Random glucose monitoring, daily from day 1 till day 8
3.5. Blood for pharmacokinetic study (2 ml of blood, sparse sampling, either one blood sample or two blood samples after the third dose of gatifloxacin or ofloxacin)

At all visits fever and clinical symptoms will be monitored (feeling better or not, fever, headache, anorexia, pain abdomen, cough, constipation, diarrhoea, vomiting, nausea, confusion, black stool, sweating/dizziness, fainting/blackouts, nocturia/polyuria or others) and recorded with particular attention to:
3.6. Any side effects of the drug
3.7. Complications of the disease (if any occur)

4. Day 8:
4.1. Patients will be re-examined by the study physicians at Patan Hospital
4.2. Blood cultures will be performed day 8
4.3. Full blood counts including white cell differential, biochemistry (SGOT, SGPT, creatinine) will be repeated
4.4. Faeces will be re-cultured day 8
4.5. Blood for typhoid diagnostic study (2 ml)

5. Day 15:
All patients will be re-examined by the study physicians at Patan Hospital.

Further follow up will be performed for six months.
Intervention typeDrug
PhaseNot Specified
Drug / device / biological / vaccine name(s)Gatifloxacin, ofloxacin
Primary outcome measure(s)

The overall failure of the treatment. Overall failure of treatment is defined as the occurrence of any one of the following (acute treatment failure plus complication plus relapse):
1. Persistent fever at day 10 of treatment
2. Blood culture positive at day 10 of treatment
3. Need for 'rescue' treatment with ceftriaxone
4. Culture confirmed relapse within 28 days of starting therapy
5. The development of any typhoid fever related complications during treatment:
5.1. Clinically significant bleeding
5.2. Fall in the Glasgow Coma Score
5.3. Perforation of the gastrointestinal tract
5.4. Admission to hospital within 28 days of starting therapy

Key secondary outcome measure(s)

1. Fever clearance time (FCT)
2. Syndromic clinical relapse occurring within 28 days of starting therapy that is thought to be due to typhoid or paratyphoid fever (fever, abdominal pain, change in bowel habit, headache, etc), blood cultures negative and no other cause identified
3. Stool carriage of Salmonella typhi or S. paratyphi at 1, 3, or 6 months

Completion date31/07/2010

Eligibility

Participant type(s)Patient
Age groupNot Specified
SexAll
Target sample size at registration200
Key inclusion criteria1. Patients give fully informed consent
2. Aged above 2 years and weigh more than 10 kg, either sex
3. Patients with fever for more than 3 days
4. Patients have no signs of severe typhoid fever, are not obtunded or shocked, are not visibly jaundiced and have no signs of gastrointestinal bleeding or any other evidence of severity
5. No previous history of hypersensitivity to either of the trial drugs
6. No known previous treatment with a fluoroquinolone antibiotic or third generation cephalosporin or macrolide within one week of hospital admission (patients who have received chloramphenicol, ampicillin, or co-trimoxazole will be included as long as they have not shown evidence of clinical response)
7. Patients are not pregnant or breast-feeding
Key exclusion criteriaDoes not comply with the above inclusion criteria
Date of first enrolment01/08/2008
Date of final enrolment31/07/2010

Locations

Countries of recruitment

  • Nepal
  • Viet Nam

Study participating centre

The Oxford University Clinical Research Unit (OUCRU)
Ho Chi Minh City
Q5
Viet Nam

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 31/10/2013 Yes No
Participant information sheet Participant information sheet 11/11/2025 11/11/2025 No Yes
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