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Nepal Undifferentiated Febrile Illness Trial (NUFIT)

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ClinicalTrials.gov Identifier: NCT02773407
Recruitment Status : Active, not recruiting
First Posted : May 16, 2016
Last Update Posted : August 30, 2019
Sponsor:
Collaborators:
University of Oxford
Wellcome Trust
Information provided by (Responsible Party):
Oxford University Clinical Research Unit, Vietnam

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

Condition or disease Intervention/treatment Phase
Undifferentiated Febrile Illness Drug: Azithromycin Drug: Co-trimoxazole Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 330 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Parallel Group, Double Blinded, 1:1, Randomized Controlled Phase III Trial of Co-trimoxazole Versus Azithromycin for the Treatment of Undifferentiated Fever In Nepal
Actual Study Start Date : May 23, 2016
Actual Primary Completion Date : August 4, 2019
Estimated Study Completion Date : August 4, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fever

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



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Fever failure [ Time Frame: over 7 days post treatment initiation ]
    defined by fever clearance time (FCT) >7 days post treatment initiation;

  2. Need rescue treatment [ Time Frame: within 63 days ]
    Requirement for rescue treatment as judged by the Research Medical Officer (RMO) and Attending Physician (AP)

  3. Microbiological failure [ Time Frame: on day 7 of treatment ]
    Blood culture positivity for S. Typhi or an S. Paratyphi

  4. Relapse [ Time Frame: within 28 days of initiation of treatment ]
    Culture-confirmed or syndromic enteric fever relapse

  5. 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

  6. 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

  7. 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



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Ages Eligible for Study:   2 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02773407


Locations
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Nepal
Nepal Civil Service Hospital
Kathmandu, Nepal
Patan Hospital
Kathmandu, Nepal
Sponsors and Collaborators
Oxford University Clinical Research Unit, Vietnam
University of Oxford
Wellcome Trust
Investigators
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Principal Investigator: Buddha Basnyat, MBBS,MSc,MD University of Oxford

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Oxford University Clinical Research Unit, Vietnam
ClinicalTrials.gov Identifier: NCT02773407     History of Changes
Other Study ID Numbers: 18NP
First Posted: May 16, 2016    Key Record Dates
Last Update Posted: August 30, 2019
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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
Keywords provided by Oxford University Clinical Research Unit, Vietnam:
Undifferentiated febrile illness
Azithromycin
Cotrimoxazole
Efficacy
Enteric fever
Fever clearance time
Additional relevant MeSH terms:
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Fever
Body Temperature Changes
Signs and Symptoms
Trimethoprim, Sulfamethoxazole Drug Combination
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Anti-Bacterial Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents