search
Back to results

Infant TB Infection Prevention Study (iTIPS)

Primary Purpose

Tuberculosis

Status
Completed
Phase
Phase 2
Locations
Kenya
Study Type
Interventional
Intervention
Isoniazid
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Tuberculosis focused on measuring M. tuberculosis infection, isoniazid, HIV-exposed infants

Eligibility Criteria

6 Weeks - 10 Weeks (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

  • Kisumu County Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Isoniazid

No Isoniazid

Arm Description

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

No INH will be administered to this arm.

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

Severe Adverse Events (SAE)
Number of infants with grade 3 or higher treatment-related adverse events as assessed by DAIDS Table for the Grading Severity of Pediatric Adverse Experiences
Combined Outcome of MTB Infection, TB Disease, and Death
Number of infants with a combined endpoint of MTB infection, TB disease, and death MTB infection as measured by IGRA or tuberculin skin test at 12 months post-enrollment TB disease including microbiologically confirmed (culture or Xpert positive), or probable TB (clinical diagnosis). Death of infant
Combined Outcome of MTB Infection Including IGRA, TST, and Additional Interferon-gamma-independent Immune Markers in QFT-Plus Supernatants
Number of infants with MTB infection as measured by IGRA, or Tuberculin skin test (>10 mm) at 12 months post-enrollment, or Interferon-gamma-independent immune markers in QFT-Plus supernatants Combined outcome will be defined as positive if IGRA OR TST OR interferon-gamma-independent marker is positive and combined outcome will be defined as negative if none of these is positive (if children do not have all three markers the definition will hold for available markers).

Full Information

First Posted
September 16, 2015
Last Updated
March 31, 2023
Sponsor
University of Washington
Collaborators
Thrasher Research Fund
search

1. Study Identification

Unique Protocol Identification Number
NCT02613169
Brief Title
Infant TB Infection Prevention Study
Acronym
iTIPS
Official Title
Preventing Mycobacterium Tuberculosis Infection in HIV-Exposed Infants
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
August 2016 (undefined)
Primary Completion Date
October 2019 (Actual)
Study Completion Date
December 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
Thrasher Research Fund

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Randomized controlled trial (RCT) of isoniazid (INH) vs. no INH to prevent Mycobacterium tuberculosis infection in HIV-exposed uninfected (HEU) infants.
Detailed Description
The purpose of this trial is to determine whether isoniazid (INH) reduces the risk of Mycobacterium tuberculosis (MTB) infection in HIV-exposed but uninfected (HEU) children, as well as to determine epidemiologic and immunologic correlates of MTB infection in HEU.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
Keywords
M. tuberculosis infection, isoniazid, HIV-exposed infants

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
300 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Isoniazid
Arm Type
Experimental
Arm Description
Isoniazid (INH) ~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months.
Arm Title
No Isoniazid
Arm Type
No Intervention
Arm Description
No INH will be administered to this arm.
Intervention Type
Drug
Intervention Name(s)
Isoniazid
Other Intervention Name(s)
INH
Intervention Description
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.
Primary Outcome Measure Information:
Title
Mycobacterium Tuberculosis (MTB) Infection
Description
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
Time Frame
at 12 months post randomization
Title
Mycobacterium Tuberculosis (MTB) Infection Cumulative Incidence
Description
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
Time Frame
at 12 months post randomization
Secondary Outcome Measure Information:
Title
Severe Adverse Events (SAE)
Description
Number of infants with grade 3 or higher treatment-related adverse events as assessed by DAIDS Table for the Grading Severity of Pediatric Adverse Experiences
Time Frame
Over 12 months after randomization
Title
Combined Outcome of MTB Infection, TB Disease, and Death
Description
Number of infants with a combined endpoint of MTB infection, TB disease, and death MTB infection as measured by IGRA or tuberculin skin test at 12 months post-enrollment TB disease including microbiologically confirmed (culture or Xpert positive), or probable TB (clinical diagnosis). Death of infant
Time Frame
Over 12 months after randomization
Title
Combined Outcome of MTB Infection Including IGRA, TST, and Additional Interferon-gamma-independent Immune Markers in QFT-Plus Supernatants
Description
Number of infants with MTB infection as measured by IGRA, or Tuberculin skin test (>10 mm) at 12 months post-enrollment, or Interferon-gamma-independent immune markers in QFT-Plus supernatants Combined outcome will be defined as positive if IGRA OR TST OR interferon-gamma-independent marker is positive and combined outcome will be defined as negative if none of these is positive (if children do not have all three markers the definition will hold for available markers).
Time Frame
Over 12 months after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Weeks
Maximum Age & Unit of Time
10 Weeks
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: HIV exposed infants Aged 6 weeks within (+ 4 weeks) Born to HIV-infected mothers Not premature and over 2.5 kg Exclusion Criteria: Infants with known exposure to active TB in household Premature and < 2.5 kg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Grace John-Stewart, MD, PhD
Organizational Affiliation
University of Washington, Dept of Global Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kisumu County Hospital
City
Kisumu
Country
Kenya

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
17085459
Citation
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.
Results Reference
background
PubMed Identifier
21732834
Citation
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.
Results Reference
background
PubMed Identifier
35607710
Citation
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.
Results Reference
result
PubMed Identifier
32564076
Citation
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.
Results Reference
derived
PubMed Identifier
31969368
Citation
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.
Results Reference
derived

Learn more about this trial

Infant TB Infection Prevention Study

We'll reach out to this number within 24 hrs