Condition category
Infections and Infestations
Date applied
16/07/2008
Date assigned
17/07/2008
Last edited
29/11/2013
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Christiane Dolececk

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

ctu01tyjan08

Study information

Scientific title

Acronym

Study hypothesis

We hypothesise that gatifloxacin is more effective than ofloxacin in the treatment of enteric fever.

Ethics approval

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

Study design

An open randomised two-way comparison trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Enteric fever (typhoid and paratyphoid fever)

Intervention

Gatifloxacin (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 type

Drug

Phase

Not Specified

Drug names

Gatifloxacin, ofloxacin

Primary outcome measures

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

Secondary outcome measures

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

Overall trial start date

01/08/2008

Overall trial end date

31/07/2010

Reason abandoned

Eligibility

Participant inclusion criteria

1. 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

Participant type

Patient

Age group

Not Specified

Gender

Both

Target number of participants

200 patients

Participant exclusion criteria

Does not comply with the above inclusion criteria

Recruitment start date

01/08/2008

Recruitment end date

31/07/2010

Locations

Countries of recruitment

Nepal

Trial participating centre

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

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

Clinical Trials and Research Governance
Manor House
John Radcliffe Hospital
Headington
Oxford
OX3 9DZ
United Kingdom

Sponsor type

University/education

Website

http://www.ox.ac.uk/

Funders

Funder type

Charity

Funder name

The Wellcome Trust (UK) (grant ref: 077078)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24282626

Publication citations

  1. Results

    Koirala S, Basnyat B, Arjyal A, Shilpakar O, Shrestha K, Shrestha R, Shrestha UM, Agrawal K, Koirala KD, Thapa SD, Karkey A, Dongol S, Giri A, Shakya M, Pathak KR, Campbell J, Baker S, Farrar J, Wolbers M, Dolecek C, Gatifloxacin versus ofloxacin for the treatment of uncomplicated enteric fever in Nepal: an open-label, randomized, controlled trial., PLoS Negl Trop Dis, 2013, 7, 10, e2523, doi: 10.1371/journal.pntd.0002523.

Additional files

Editorial Notes