Trial Outcomes & Findings for Infant TB Infection Prevention Study (NCT NCT02613169)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

300 participants

Primary outcome timeframe

at 12 months post randomization

Results posted on

2023-04-28

Participant Flow

Participant milestones

Participant milestones
Measure	Isoniazid Isoniazid (INH) \~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months. Isoniazid: 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.	No Isoniazid No INH will be administered to this arm.
Overall Study STARTED	150	150
Overall Study COMPLETED	132	133
Overall Study NOT COMPLETED	18	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Isoniazid Isoniazid (INH) \~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months. Isoniazid: 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.	No Isoniazid No INH will be administered to this arm.
Overall Study Withdrawal by Subject	4	1
Overall Study Lost to Follow-up	0	5
Overall Study HIV	0	2
Overall Study No TB infection endpoint	14	9

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Isoniazid n=150 Participants Isoniazid (INH) \~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months. Isoniazid: 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.	No Isoniazid n=150 Participants No INH will be administered to this arm.	Total n=300 Participants Total of all reporting groups
Age, Categorical <=18 years	150 Participants n=150 Participants	150 Participants n=150 Participants	300 Participants n=300 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=150 Participants	0 Participants n=150 Participants	0 Participants n=300 Participants
Age, Categorical >=65 years	0 Participants n=150 Participants	0 Participants n=150 Participants	0 Participants n=300 Participants
Age, Continuous	6.3 weeks n=150 Participants	6.3 weeks n=150 Participants	6.3 weeks n=300 Participants
Sex: Female, Male Female	71 Participants n=150 Participants	71 Participants n=150 Participants	142 Participants n=300 Participants
Sex: Female, Male Male	79 Participants n=150 Participants	79 Participants n=150 Participants	158 Participants n=300 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Kenya	150 participants n=150 Participants	150 participants n=150 Participants	300 participants n=300 Participants

PRIMARY outcome

Timeframe: at 12 months post randomization

Population: Final analysis 132 in Isoniazid (14 without endpoint and 4 discontinued) and 133 in No Isoniazid arm (9 without primary endpoint, 8 discontinued)

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

Outcome measures

Outcome measures
Measure	Isoniazid n=132 Participants Isoniazid (INH) \~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months. Isoniazid: 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.	No Isoniazid n=133 Participants No INH will be administered to this arm.
Mycobacterium Tuberculosis (MTB) Infection	10 participants	18 participants

PRIMARY outcome

Timeframe: at 12 months post randomization

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

Outcome measures

Outcome measures
Measure	Isoniazid n=132 Participants Isoniazid (INH) \~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months. Isoniazid: 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.	No Isoniazid n=133 Participants No INH will be administered to this arm.
Mycobacterium Tuberculosis (MTB) Infection Cumulative Incidence	7.0 TB infections/100 person years	13.4 TB infections/100 person years

SECONDARY outcome

Timeframe: Over 12 months after randomization

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

Outcome measures

Outcome measures
Measure	Isoniazid n=150 Participants Isoniazid (INH) \~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months. Isoniazid: 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.	No Isoniazid n=150 Participants No INH will be administered to this arm.
Severe Adverse Events (SAE)	21 Participants	16 Participants

SECONDARY outcome

Timeframe: Over 12 months after randomization

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

Outcome measures

Outcome measures
Measure	Isoniazid n=146 Participants Isoniazid (INH) \~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months. Isoniazid: 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.	No Isoniazid n=142 Participants No INH will be administered to this arm.
Combined Outcome of MTB Infection, TB Disease, and Death	11 Participants	19 Participants

SECONDARY outcome

Timeframe: Over 12 months after randomization

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).

Outcome measures

Outcome data not reported

Adverse Events

Isoniazid

Serious events: 21 serious events

Other events: 0 other events

Deaths: 0 deaths

No Isoniazid

Serious events: 16 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Isoniazid n=150 participants at risk Isoniazid (INH) \~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months. Isoniazid: 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.	No Isoniazid n=150 participants at risk No INH will be administered to this arm.
Infections and infestations HIV infection	0.00% 0/150 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale	1.3% 2/150 • Number of events 2 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale
Respiratory, thoracic and mediastinal disorders Pneumonia/URTI	3.3% 5/150 • Number of events 5 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale	3.3% 5/150 • Number of events 5 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale
Gastrointestinal disorders Gastroenteritis	5.3% 8/150 • Number of events 8 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale	2.0% 3/150 • Number of events 3 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale
Infections and infestations Malaria	8.0% 12/150 • Number of events 12 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale	4.0% 6/150 • Number of events 6 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale
Surgical and medical procedures Corrective surgery for spina bifida	0.00% 0/150 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale	0.67% 1/150 • Number of events 1 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale
Surgical and medical procedures Corrective surgery for cleft palate	0.67% 1/150 • Number of events 1 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale	0.00% 0/150 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale
Surgical and medical procedures Corrective surgery for encephalocele	0.67% 1/150 • Number of events 1 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale	0.00% 0/150 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale
Injury, poisoning and procedural complications Burns	0.67% 1/150 • Number of events 1 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale	0.00% 0/150 • Adverse event data were collected throughout the study, for two years, two months. Adverse events include Grade ≥3 severe adverse events by DAIDS scale

Other adverse events

Adverse event data not reported

Additional Information

Dr. Sylvia M. LaCourse

University of Washington

Phone: 206-616-5978

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place