Condition category
Infections and Infestations
Date applied
11/04/2006
Date assigned
11/04/2006
Last edited
20/03/2013
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 Buddha Basnyat

ORCID ID

Contact details

Patan Hospital
Kathmandu
-
Nepal
+977 (0)1 44 34642/18774
rishibas@wlink.com.np

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

061330; OXTREC 002-06

Study information

Scientific title

Acronym

ED

Study hypothesis

There has been a steady change in Kathmandu in the sensitivity of Salmonella typhi (the bacteria that causes typhoid fever) to all antibiotics. In Kathmandu in 2005 less than 5% of isolates are resistant to first line antibiotics including Chloramphenicol but they do show significantly poorer clinical response to the older fluoroquinolones (Ciprofloxacin and Ofloxacin) with high rates of Nalidixic acid resistance. There has been interest in Kathmandu and in the Indian Sub-Continent about returning to the use of the classical antibiotics for typhoid including Chloramphenicol. It is unclear in this environment, whether this is a reliable therapy for enteric fever or whether Gatifloxacin, a new generation and affordable floroquinolone, would be the better choice.

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Typhoid fever

Intervention

Gatifloxacin versus Chloramphenicol.

Added as of 20/09/2007:
This trial was stopped temporarily in September 2006 at the request of the Nepal Health Research Council and Department of Drug Administration after the reports of dysglycaemia associated with gatifloxacin.

The trial was resumed on Dec 2006 after the ethical committee and the Drug Administration authority were assured that dysglycaemia was not a problem in the young population who are most affected by enteric fever and all the patients in the trial were monitored closely for any dysglycaemia by fingerprick glucose testing.

Please note that due to the reasons stated above, the anticipated end date of this trial has changed. The previous end date of this trial was 30th April 2007.

Intervention type

Drug

Phase

Not Specified

Drug names

Gatifloxacin, Chloramphenicol

Primary outcome measures

Failure of treatment defined as the occurrence of any one of the following:
1. Persistent fever at day ten of treatment
2. Failure to clear completely the admission symptoms at day ten
3. Blood culture positive at day ten of treatment
4. Need for 'rescue' treatment with ceftriaxone
5. Culture confirmed relapse within 28 days of starting therapy
6. The development on treatment of any complication:
6.1 Clinically significant bleeding
6.2. Fall in the Glasgow Coma Score
6.3. Perforation of the gastrointestinal tract
6.4. Admission to hospital within 28 days of starting therapy

Secondary outcome measures

No secondary outcome measures

Overall trial start date

01/05/2006

Overall trial end date

30/06/2008

Reason abandoned

This trial was stopped in September 2006 but has since restarted again (see interventions for more details of this - 20/09/07).
In the light of the reports on dysglycaemia in elderly patients in North American the Dept of Drug Administration (DDA) in Nepal have asked us to provide some additional information on Gatifloxacin. Whilst providing this additional information and following discussion with the DDA and the Nepal Health Research Council, we have suspended the study.

As the investigators, we have had no cause for concern during the study and have not identified any problems with glycaemic control on history taking, regular blood glucose monitoring and during the follow up of the study. We are in the process of providing the additional information requested and will let you know of the decision of the DDA as soon as we know of it.

We hope that we will be able to restart the study following their recommendation. At the time of suspension we have recruited 404 patients, 180 with confirmed enteric fever. As a randomised study we do not feel that the suspension has an impact on the study conduct whilst we wait for the decision.

Eligibility

Participant inclusion criteria

Any patient with suspected uncomplicated enteric fever who gives consent.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

320

Participant exclusion criteria

1. No consent
2. Pregnancy

Recruitment start date

01/05/2006

Recruitment end date

30/06/2008

Locations

Countries of recruitment

Nepal

Trial participating centre

Patan Hospital
Kathmandu
-
Nepal

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

University Offices
Wellington Square
Oxford
OX1 2JD
United Kingdom
+44 (0)1865 270143
research.services@admin.ox.ac.uk

Sponsor type

University/education

Website

http://www.ox.ac.uk

Funders

Funder type

Charity

Funder name

The Wellcome Trust (UK) (grant ref: 061330)

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

1. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21531174

Publication citations

  1. Results

    Arjyal A, Basnyat B, Koirala S, Karkey A, Dongol S, Agrawaal KK, Shakya N, Shrestha K, Sharma M, Lama S, Shrestha K, Khatri NS, Shrestha U, Campbell JI, Baker S, Farrar J, Wolbers M, Dolecek C, Gatifloxacin versus chloramphenicol for uncomplicated enteric fever: an open-label, randomised, controlled trial., Lancet Infect Dis, 2011, 11, 6, 445-454, doi: 10.1016/S1473-3099(11)70089-5.

Additional files

Editorial Notes