Nepal Undifferentiated Febrile Illness Trial (NUFIT)

December 5, 2023 updated by: Oxford University Clinical Research Unit, Vietnam

Parallel Group, Double Blinded, 1:1, Randomized Controlled Phase III Trial of Co-trimoxazole Versus Azithromycin for the Treatment of Undifferentiated Fever In Nepal

The purpose of the study is to determine whether azithromycin or cotrimoxazole is the best empirical treatment for undifferentiated febrile illness in Nepal

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Fever is one of the most common presenting symptoms of patients presenting to health centers in Nepal. Many of the times, it is difficult to diagnose the cause of the fever by initial history, clinical examination and basic laboratory tests and the patents are treated as presumed enteric fever or fever without focus needing antimicrobials. In fact there are various causes of similarly presenting febrile illnesses including typhoid, paratyphoid, murine typhus, scrub typhus etc.

Many of the traditionally used drugs including fluoroquinolones are now resistant against enteric fever in south asia. Oral azithromycin is now commonly used to treat undifferentiated febrile illness and remains effective against enteric fever. Many physicians now also use co-trimoxazole as it was very commonly used in the treatment of enteric fever in the past. Resistance to co-trimoxazole emerged two decades ago, but has subsequently largely disappeared and nearly all Salmonella Typhi and Paratyphi A strains from Nepal are now susceptible. Anecdotal reports claim that it seems to work very well against undifferentiated febrile illness in Nepal; it is largely stocked in government health facilities and is a popular and cheap treatment option.

Both azithromycin and co-trimoxazole are available in Nepal and are extensively used in the treatment of undifferentiated febrile illness. Therefore it is important to know the better oral option to treat enteric fever and other febrile illnesses and also to have an alternative oral treatment in case resistance to azithromycin emerges.

The investigators purpose to conduct a head to head, parallel group, 1:1, double blinded randomized controlled trial to compare azithromycin and co-trimoxazole for the treatment of undifferentiated febrile illness and determine the best empirical treatment for undifferentiated febrile illness in Nepal.

Study Type

Interventional

Enrollment (Actual)

330

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Nepal
      • Kathmandu, Nepal
        • Patan Hospital
      • Kathmandu, Nepal
        • Nepal Civil Service Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 61 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Fever of ≥ 38.0°C and for ≥4 days without a focus of infection
  • ≥ 2 years and <65 years of age
  • Able to take tablets orally
  • Patient residing in Kathmandu Valley
  • Able to come for follow up
  • Can be reached by telephone/mobile phone 24 hours a day.
  • Written informed consent to participate in the study including assent for minors in addition to parental consent.

Exclusion Criteria:

  • Fever >14 days
  • Pregnancy
  • Obtundation
  • Shock
  • Visible jaundice
  • Presence of signs of gastrointestinal bleeding
  • History of hypersensitivity to either of the trial drugs
  • Patient requiring intravenous antibiotic or hospital admission for any reason.
  • Contraindication of drug for any reason (e.g. drug interactions).
  • Any patient fulfilling inclusion criteria but already on antimicrobials and responding clinically to the treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group A
Azithromycin tablets 20mg/kg/day for 7 days (Maximum dose 1000mg/day)
Drug: Azithromycin
Active Comparator: Group B
Co-trimoxazole tablets (Trimethoprim 10 mg/kg+Sulphamethoxazole 50 mg/kg) in two divided doses everyday for 7 days (maximum 3000mg/day)
Drug: Co-trimoxazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fever clearance time
Time Frame: at least 2 days
time from the first dose of a study drug until a temperature ≤37.5°C for at least 2 days
at least 2 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fever failure
Time Frame: over 7 days post treatment initiation
defined by fever clearance time (FCT) >7 days post treatment initiation;
over 7 days post treatment initiation
Need rescue treatment
Time Frame: within 63 days
Requirement for rescue treatment as judged by the Research Medical Officer (RMO) and Attending Physician (AP)
within 63 days
Microbiological failure
Time Frame: on day 7 of treatment
Blood culture positivity for S. Typhi or an S. Paratyphi
on day 7 of treatment
Relapse
Time Frame: within 28 days of initiation of treatment
Culture-confirmed or syndromic enteric fever relapse
within 28 days of initiation of treatment
The development of any complication
Time Frame: within 28 days of initiation of treatment
any complication: e.g. clinically significant bleeding, fall in the Glasgow Coma Score, perforation of the gastrointestinal tract and hospital admission
within 28 days of initiation of treatment
Time-to-treatment failure
Time Frame: within 63 days
the time from the first dose of treatment until the date of the earliest failure event
within 63 days
Adverse events
Time Frame: within 63 days
grade 3/4 adverse events, serious adverse events, adverse events of any grade leading to modification of study drug dose or interruption/early discontinuation
within 63 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oxford University Clinical Research Unit, Vietnam

Collaborators

University of Oxford
Wellcome Trust

Investigators

  • Principal Investigator: Buddha Basnyat, MBBS,Msc,MD, University of Oxford

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 23, 2016

Primary Completion (Actual)

August 4, 2019

Study Completion (Actual)

August 4, 2019

Study Registration Dates

First Submitted

May 5, 2016

First Submitted That Met QC Criteria

May 13, 2016

First Posted (Estimated)

May 16, 2016

Study Record Updates

Last Update Posted (Estimated)

December 6, 2023

Last Update Submitted That Met QC Criteria

December 5, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18NP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymised individual participant data will be made available to researcher and public as a supporting material via open access journal and/or upon request by qualified research groups

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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