Infant TB Infection Prevention Study

NCT02613169 | Completed Phase 2 Results DMC

• 1 other identifier: STUDY00000341
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized controlled trial (RCT) of isoniazid (INH) vs. no INH to prevent Mycobacterium tuberculosis infection in HIV-exposed uninfected (HEU) infants.

Conditions

Tuberculosis

Keywords

M. tuberculosis infection; isoniazid; HIV-exposed infants

Outcome Measures

Primary Outcomes (2)

• Mycobacterium Tuberculosis (MTB) Infection

  Among HEU infants enrolled at approximately 6 weeks of age, compare the risk of acquiring MTB infection during 1 year of follow-up in infants randomized to receive INH vs. no INH using an interferon-gamma release (IGRA) QuantiFERON-TB Gold Plus (QFT-Plus) assay or tuberculin skin test as part of a composite endpoint to determine MTB infection status

  at 12 months post randomization

• Mycobacterium Tuberculosis (MTB) Infection Cumulative Incidence

  Among HEU infants enrolled at approximately 6 weeks of age, compare the risk of acquiring MTB infection during 1 year of follow-up in infants randomized to receive INH vs. no INH using an interferon-gamma release (IGRA) QuantiFERON-TB Gold Plus (QFT-Plus) assay or tuberculin skin test as part of a composite endpoint to determine MTB infection status

  at 12 months post randomization

Secondary Outcomes (3)

• Severe Adverse Events (SAE)

  Over 12 months after randomization

• Combined Outcome of MTB Infection, TB Disease, and Death

  Over 12 months after randomization

• Combined Outcome of MTB Infection Including IGRA, TST, and Additional Interferon-gamma-independent Immune Markers in QFT-Plus Supernatants

  Over 12 months after randomization

Study Arms (2)

Isoniazid

EXPERIMENTAL

Isoniazid (INH) \~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months.

Drug: Isoniazid

No Isoniazid

NO INTERVENTION

No INH will be administered to this arm.

Interventions

Isoniazid DRUG

HIV-exposed uninfected infants will be randomized to receive either INH or no INH daily for 12 months for the prevention of Mycobacterium tuberculosis (MTB) infection.

Also known as: INH

Isoniazid

Eligibility Criteria

• Age: 6 Weeks - 10 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• HIV exposed infants
• Aged 6 weeks within (+ 4 weeks)
• Born to HIV-infected mothers
• Not premature and over 2.5 kg

You may not qualify if:

• Infants with known exposure to active TB in household
• Premature and \< 2.5 kg

Sponsors & Collaborators

• University of Washington: lead
• Thrasher Research Fund: collaborator

Study Sites (1)

Kisumu County Hospital

Kisumu, Kenya

Location

Related Publications (5)

• Zar HJ, Cotton MF, Strauss S, Karpakis J, Hussey G, Schaaf HS, Rabie H, Lombard CJ. Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial. BMJ. 2007 Jan 20;334(7585):136. doi: 10.1136/bmj.39000.486400.55. Epub 2006 Nov 3.

  PMID: 17085459 BACKGROUND

• Madhi SA, Nachman S, Violari A, Kim S, Cotton MF, Bobat R, Jean-Philippe P, McSherry G, Mitchell C; P1041 Study Team. Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children. N Engl J Med. 2011 Jul 7;365(1):21-31. doi: 10.1056/NEJMoa1011214.

  PMID: 21732834 BACKGROUND

• LaCourse SM, Escudero JN, Mecha J, Warr AJ, Richardson BA, Carimo N, Cranmer LM, Maleche-Obimbo E, Matemo D, Kinuthia J, Hawn TR, John-Stewart G. Cumulative Mycobacterium tuberculosis Infection Incidence (Measured Primarily by Tuberculin Skin Test) Among Infants With Human Immunodeficiency Virus Exposure: Observational Follow-up of an Isoniazid Prophylaxis Trial. Clin Infect Dis. 2022 Dec 19;75(12):2253-2256. doi: 10.1093/cid/ciac393.

  PMID: 35607710 RESULT

• LaCourse SM, Richardson BA, Kinuthia J, Warr AJ, Maleche-Obimbo E, Matemo D, Cranmer LM, Mecha J, Escudero JN, Hawn TR, John-Stewart G. A Randomized Controlled Trial of Isoniazid to Prevent Mycobacterium tuberculosis Infection in Kenyan Human Immunodeficiency Virus-Exposed Uninfected Infants. Clin Infect Dis. 2021 Jul 15;73(2):e337-e344. doi: 10.1093/cid/ciaa827.

  PMID: 32564076 DERIVED

• LaCourse SM, Richardson BA, Kinuthia J, Warr AJ, Maleche-Obimbo E, Matemo D, Cranmer LM, Escudero JN, Hawn TR, John-Stewart GC. Infant TB Infection Prevention Study (iTIPS): a randomised trial protocol evaluating isoniazid to prevent M. tuberculosis infection in HIV-exposed uninfected children. BMJ Open. 2020 Jan 21;10(1):e034308. doi: 10.1136/bmjopen-2019-034308.

  PMID: 31969368 DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

Isoniazid

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Sylvia M. LaCourse
• Organization: University of Washington

sylvial2@uw.edu

206-616-5978

Study Officials

• Grace John-Stewart, MD, PhD

  University of Washington, Dept of Global Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Global Health, Medicine, Epidemiology, Pediatrics

Study Record Dates

• First Submitted: September 16, 2015
• First Posted: November 24, 2015
• Study Start: August 1, 2016
• Primary Completion: October 1, 2019
• Study Completion: December 1, 2020
• Last Updated: April 28, 2023
• Results First Posted: June 10, 2021

Record last verified: 2023-03

Locations

KE (1)