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 measure
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 (if study stopped)
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
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
Basic results (scientific)
Publication list
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24282626
Publication citations
-
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.