Nepal Undifferentiated Febrile Illness Trial

NCT ID: NCT02773407

Last Updated: 2023-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

330 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-23

Study Completion Date

2019-08-04

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Undifferentiated Febrile Illness

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Undifferentiated febrile illness Azithromycin Cotrimoxazole Efficacy Enteric fever Fever clearance time

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Group A

Azithromycin tablets 20mg/kg/day for 7 days (Maximum dose 1000mg/day)

Group Type ACTIVE_COMPARATOR

Azithromycin

Intervention Type DRUG

Group B

Co-trimoxazole tablets (Trimethoprim 10 mg/kg+Sulphamethoxazole 50 mg/kg) in two divided doses everyday for 7 days (maximum 3000mg/day)

Group Type ACTIVE_COMPARATOR

Co-trimoxazole

Intervention Type DRUG

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Azithromycin

Intervention Type DRUG

Co-trimoxazole

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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).
Minimum Eligible Age

2 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Oxford

OTHER

Sponsor Role collaborator

Wellcome Trust

OTHER

Sponsor Role collaborator

Oxford University Clinical Research Unit, Vietnam

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Buddha Basnyat, MBBS,MSc,MD

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Nepal Civil Service Hospital

Kathmandu, , Nepal

Site Status

Patan Hospital

Kathmandu, , Nepal

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Nepal

References

Explore related publications, articles, or registry entries linked to this study.

Crump JA, Kirk MD. Estimating the Burden of Febrile Illnesses. PLoS Negl Trop Dis. 2015 Dec 3;9(12):e0004040. doi: 10.1371/journal.pntd.0004040. eCollection 2015 Dec. No abstract available.

Reference Type BACKGROUND
PMID: 26633014 (View on PubMed)

Zimmerman MD, Murdoch DR, Rozmajzl PJ, Basnyat B, Woods CW, Richards AL, Belbase RH, Hammer DA, Anderson TP, Reller LB. Murine typhus and febrile illness, Nepal. Emerg Infect Dis. 2008 Oct;14(10):1656-9. doi: 10.3201/eid1410.080236.

Reference Type BACKGROUND
PMID: 18826840 (View on PubMed)

Thompson CN, Blacksell SD, Paris DH, Arjyal A, Karkey A, Dongol S, Giri A, Dolecek C, Day N, Baker S, Thwaites G, Farrar J, Basnyat B. Undifferentiated febrile illness in Kathmandu, Nepal. Am J Trop Med Hyg. 2015 Apr;92(4):875-878. doi: 10.4269/ajtmh.14-0709. Epub 2015 Feb 9.

Reference Type BACKGROUND
PMID: 25667056 (View on PubMed)

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 Oct 31;7(10):e2523. doi: 10.1371/journal.pntd.0002523. eCollection 2013.

Reference Type BACKGROUND
PMID: 24282626 (View on PubMed)

Arjyal A , Basnyat B, Nhan HT, Koirala S, Giri A, Joshi N, et al. A randomised controlled trial of gatifloxacin versus ceftriaxone for the treatment of uncomplicated enteric fever in Nepal. Submitted. 2015;3099(15):1-11

Reference Type BACKGROUND

Dolecek C, Tran TP, Nguyen NR, Le TP, Ha V, Phung QT, Doan CD, Nguyen TB, Duong TL, Luong BH, Nguyen TB, Nguyen TA, Pham ND, Mai NL, Phan VB, Vo AH, Nguyen VM, Tran TT, Tran TC, Schultsz C, Dunstan SJ, Stepniewska K, Campbell JI, To SD, Basnyat B, Nguyen VV, Nguyen VS, Nguyen TC, Tran TH, Farrar J. A multi-center randomised controlled trial of gatifloxacin versus azithromycin for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. PLoS One. 2008 May 21;3(5):e2188. doi: 10.1371/journal.pone.0002188.

Reference Type BACKGROUND
PMID: 18493312 (View on PubMed)

Parry CM, Ho VA, Phuong le T, Bay PV, Lanh MN, Tung le T, Tham NT, Wain J, Hien TT, Farrar JJ. Randomized controlled comparison of ofloxacin, azithromycin, and an ofloxacin-azithromycin combination for treatment of multidrug-resistant and nalidixic acid-resistant typhoid fever. Antimicrob Agents Chemother. 2007 Mar;51(3):819-25. doi: 10.1128/AAC.00447-06. Epub 2006 Dec 4.

Reference Type BACKGROUND
PMID: 17145784 (View on PubMed)

Chinh NT, Parry CM, Ly NT, Ha HD, Thong MX, Diep TS, Wain J, White NJ, Farrar JJ. A randomized controlled comparison of azithromycin and ofloxacin for treatment of multidrug-resistant or nalidixic acid-resistant enteric fever. Antimicrob Agents Chemother. 2000 Jul;44(7):1855-9. doi: 10.1128/AAC.44.7.1855-1859.2000.

Reference Type BACKGROUND
PMID: 10858343 (View on PubMed)

Chand HJ, Rijal KR, Neupane B, Sharma VK, Jha B. Re-emergence of susceptibility to conventional first line drugs in Salmonella isolates from enteric fever patients in Nepal. J Infect Dev Ctries. 2014 Nov 13;8(11):1483-7. doi: 10.3855/jidc.4228.

Reference Type BACKGROUND
PMID: 25390062 (View on PubMed)

Pandit A, Arjyal A, Day JN, Paudyal B, Dangol S, Zimmerman MD, Yadav B, Stepniewska K, Campbell JI, Dolecek C, Farrar JJ, Basnyat B. An open randomized comparison of gatifloxacin versus cefixime for the treatment of uncomplicated enteric fever. PLoS One. 2007 Jun 27;2(6):e542. doi: 10.1371/journal.pone.0000542.

Reference Type BACKGROUND
PMID: 17593957 (View on PubMed)

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 Jun;11(6):445-54. doi: 10.1016/S1473-3099(11)70089-5. Epub 2011 Apr 29.

Reference Type BACKGROUND
PMID: 21531174 (View on PubMed)

Giri A, Karkey A, Dangol S, Arjyal A, Pokharel S, Rijal S, Gajurel D, Sharma R, Lamsal K, Shrestha P, Prajapati G, Pathak S, Shrestha SR, K C RK, Pandey S, Thapa A, Shrestha N, Thapa RK, Poudyal B, Phuong DNT, Baker S, Kestelyn E, Geskus R, Thwaites G, Basnyat B. Trimethoprim-sulfamethoxazole Versus Azithromycin for the Treatment of Undifferentiated Febrile Illness in Nepal: A Double-blind, Randomized, Placebo-controlled Trial. Clin Infect Dis. 2021 Oct 5;73(7):e1478-e1486. doi: 10.1093/cid/ciaa1489.

Reference Type DERIVED
PMID: 32991678 (View on PubMed)

Pokharel S, Basnyat B, Arjyal A, Mahat SP, Kc RK, Bhuju A, Poudyal B, Kestelyn E, Shrestha R, Phuong DNT, Thapa R, Karki M, Dongol S, Karkey A, Wolbers M, Baker S, Thwaites G. Co-trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: study protocol for a randomized controlled trial. Trials. 2017 Oct 2;18(1):450. doi: 10.1186/s13063-017-2199-6.

Reference Type DERIVED
PMID: 28969659 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

18NP

Identifier Type: -

Identifier Source: org_study_id