Nepal Undifferentiated Febrile Illness Trial

NCT02773407 | Completed Phase 3 DMC

• 1 other identifier: 18NP
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 2

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

Conditions

Undifferentiated Febrile Illness

Keywords

Undifferentiated febrile illness; Azithromycin; Cotrimoxazole; Efficacy; Enteric fever; Fever clearance time

Outcome Measures

Primary Outcomes (1)

• Fever clearance time

  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 Outcomes (7)

• Fever failure

  over 7 days post treatment initiation

• Need rescue treatment

  within 63 days

• Microbiological failure

  on day 7 of treatment

• Relapse

  within 28 days of initiation of treatment

• The development of any complication

  within 28 days of initiation of treatment

Study Arms (2)

Group A

ACTIVE COMPARATOR

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

Drug: Azithromycin

Group B

ACTIVE COMPARATOR

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

Interventions

Azithromycin DRUG

Group A

Co-trimoxazole DRUG

Group B

Eligibility Criteria

• Age: 2 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Oxford University Clinical Research Unit, Vietnam: lead
• University of Oxford: collaborator
• Wellcome Trust: collaborator

Study Sites (2)

Nepal Civil Service Hospital

Kathmandu, Nepal

Location

Patan Hospital

Kathmandu, Nepal

Location

Related Publications (13)

• 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.

  PMID: 26633014 BACKGROUND

• 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.

  PMID: 18826840 BACKGROUND

• 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.

  PMID: 25667056 BACKGROUND

• 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.

  PMID: 24282626 BACKGROUND

• 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

  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.

  PMID: 18493312 BACKGROUND

• 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.

  PMID: 17145784 BACKGROUND

• 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.

  PMID: 10858343 BACKGROUND

• 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.

  PMID: 25390062 BACKGROUND

• 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.

  PMID: 17593957 BACKGROUND

• 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.

  PMID: 21531174 BACKGROUND

• 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.

  PMID: 32991678 DERIVED

• 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.

  PMID: 28969659 DERIVED

MeSH Terms

Conditions

Typhoid Fever

Interventions

Azithromycin; Trimethoprim, Sulfamethoxazole Drug Combination

Condition Hierarchy (Ancestors)

Salmonella Infections; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Buddha Basnyat, MBBS,MSc,MD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2016
• First Posted: May 16, 2016
• Study Start: May 23, 2016
• Primary Completion: August 4, 2019
• Study Completion: August 4, 2019
• Last Updated: December 6, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

NE (2)