Evaluating the Safety of Immediate Versus Deferred Isoniazid Preventive Therapy Among HIV-Infected Pregnant Women

• Register: ClinicalTrials.gov
• Last refreshed on: 15 November 2021
• Main ID: NCT01494038
• Date of registration: 14/12/2011
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Evaluating the Safety of Immediate Versus Deferred Isoniazid Preventive Therapy Among HIV-Infected Pregnant Women
• Scientific title: A Phase IV Randomized Double-Blind Placebo-Controlled Trial to Evaluate the Safety of Immediate (Antepartum-Initiated) Versus Deferred (Postpartum-Initiated) Isoniazid Preventive Therapy Among HIV-Infected Women in High Tuberculosis (TB) Incidence Settings
• Date of first enrolment: August 19, 2014
• Target sample size: 956
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01494038
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: Double (Participant, Care Provider).
• Phase: Phase 4

Countries of recruitment

Botswana, Haiti, India, South Africa, Tanzania, Thailand, Uganda, Zimbabwe

Contacts

• Name: Amita Gupta, MD, MHS
• Affiliation: Johns Hopkins University

Key inclusion & exclusion criteria

Inclusion Criteria:

- Documented HIV-1 infection, defined as positive results from two samples collected at
different time points. All samples tested must be whole blood, serum, or plasma. More
information on this criterion can be found in the protocol.

- Documented HIV treatment, according to World Health Organization (WHO) guidelines, for
prevention of mother-to-child transmission (PMTCT) and standard of care for HIV
infection

- Pregnant females age 18 years or older

- Pregnant females between greater than or equal to 13 and less than 18 who are able and
willing to provide signed informed consent under local law or pregnant females unable
to consent under local law whose parents/legal guardians provide consent or "minimum
age of consent according to locally applicable laws or regulations"

- Pregnancy gestational age confirmed by best available method at site to be greater
than or equal to 14 weeks through less than or equal to 34 weeks (34 weeks, 6 days)

- Weight greater than or equal to 35 kg at screening

- The following laboratory values obtained within 30 days prior to study entry:

- Absolute neutrophil count (ANC) greater than or equal to 750 cells/mm^3

- Hemoglobin greater than or equal to 7.5 g/dL

- Platelet count greater than or equal to 50,000/mm^3

- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT),
alkaline phosphatase (ALT)/serum glutamic pyruvic transaminase (SGPT), and total
bilirubin less than or equal to 1.25 times the upper limit of normal (ULN).
(Note: If participant is taking atazanavir, direct bilirubin may be used to
determine eligibility.)

- Intent to remain in current geographical area of residence for the duration of the
study

Exclusion Criteria:

- Any woman with a positive TB symptom screen per WHO guidelines, including any one or
more of the following: any cough, fever, self-reported weight loss, or night sweats.
Note: If a potential participant is found to be negative for TB upon further testing,
the participant may be rescreened for the study.

- Any positive acid-fast bacillus (AFB) smear, Xpert, or any other rapid TB screening
test or culture from any site within the past 12 weeks, or chest radiograph (x-ray)
with findings suggestive of active TB, or clinician suspects active TB

- Known exposure to AFB smear-positive active TB case within past 12 weeks prior to
study entry

- Reported INH exposure (more than 30 days) in the past year prior to study entry

- Receipt of any TB or atypical mycobacteria therapy for more than 30 days in the past
year

- Evidence of acute hepatitis, such as jaundice, dark urine (not concentrated urine),
and/or acholic stools sustained for more than 3 days within 90 days prior to entry.
More information on this criterion can be found in the protocol.

- Grade 1 or higher peripheral neuropathy. More information on this criterion can be
found in the protocol.

- History of acute systemic adverse reaction or allergy to INH

- Known current heavy alcohol use (more than 2 drinks per week) or alcohol exposure
that, in the investigator's opinion, would compromise participation and the outcome of
this study

- Presence of new AIDS-defining opportunistic infection that has been treated less than
30 days prior to study entry

- Receipt of an investigational agent or chemotherapy for active malignancy within 30
days prior to study entry

- Any clinically significant diseases (other than HIV infection) or clinically
significant findings during the screening medical history or physical examination
that, in the investigator's opinion, would compromise participation and the outcome of
this study



Age minimum: 13 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

HIV Infections

Tuberculosis

Intervention(s)

Drug: Isoniazid (INH)

Drug: Placebo for isoniazid (INH)

Primary Outcome(s)

Incidence Rate of Combined Endpoint: Grade 3 or Higher Adverse Events (AEs) Related to Treatment, or AE Causing Discontinuation of Treatment [Time Frame: Measured from study entry through Week 48 after birth]

Secondary Outcome(s)

Incidence Rate of Tuberculosis (TB) Among Infants [Time Frame: Measured from study entry through Week 48 after birth]

Incidence Rate, up to 12 Weeks Postpartum, of Hepatotoxicity, Defined by DAIDS, Any Cause [Time Frame: Measured from study start through 12 weeks postpartum]

Number of Infants Hospitalized [Time Frame: Measured from study entry through Week 48 after birth]

Number of Infants Which Are HIV-infected [Time Frame: Measured from study entry through study Week 44]

Incidence Rate of Infant Death [Time Frame: Measured from study entry through Week 48 after birth]

Incidence Rate, Antepartum, of Hepatotoxicity, Defined by DAIDS, Related to Treatment [Time Frame: Measured from study entry through delivery]

Agreement Between IGRA and TST TB Test Results, Infant [Time Frame: Measured at week 44 after birth]

Agreement Between Interferon-gamma Release Assay (IGRA) TB Test and Tuberculin Skin Test (TST) Results, Women at Delivery [Time Frame: Measured at delivery]

Incidence Rate, to 12 Weeks Postpartum, of Hepatotoxicity, Protocol-specific Definition, Any Cause [Time Frame: Measured from study entry through 12 weeks postpartum]

Incidence Rate of Maternal Deaths [Time Frame: Measured from study entry through Week 48 postpartum]

Number of Women by Level of Adherence to Prescribed Regimen, as Assessed by Self-report [Time Frame: Adherence reported every 4 weeks during active treatment; study entry through week 28 for Arm A, week 12 postpartum through week 40 postpartum for Arm B]

Incidence Rate, up to 12 Weeks Postpartum, of Hepatotoxicity, Defined by DAIDS, Related to Treatment [Time Frame: Measured from study start through 12 weeks postpartum]

Incidence Rate of Combined Endpoints: Maternal TB or Maternal Death [Time Frame: Measured from study entry through Week 48 after birth]

Incidence Rate, Antepartum, of Hepatotoxicity, Defined by Protocol-specific Definition of Hepatotoxicity, Related to Treatment [Time Frame: Measured from study entry through delivery]

Incidence Rate of Combined Endpoints: Maternal TB, Maternal Death, Infant TB, or Infant Death [Time Frame: Measured from study entry through Week 48 after birth]

Number of Mothers With a Fetus Small for Gestational Age [Time Frame: Measured at delivery]

Number of Mothers With an Adverse Pregnancy Outcome: Spontaneous Abortion, Stillbirth, Premature Birth, Low Birth Weight, or Congenital Anomaly [Time Frame: Measured from study entry through Week 48 after birth]

Incidence Rate, Antepartum, of Hepatotoxicity, Protocol-specific Definition, Any Cause [Time Frame: Measured from study entry through delivery]

Incidence Rate, Antepartum, of Grade 3 or Higher AE [Time Frame: Measured from study entry through end of pregnancy]

Number of Infants With Grade 3 or Higher Clinical or Laboratory AE [Time Frame: Measured from study entry through Week 48 after birth]

Number of Mothers With an Infant With a Congenital Anomaly [Time Frame: Measured from study entry through Week 48 after birth]

Agreement Between IGRA and TST TB Tests, Women at 44 Weeks Postpartum [Time Frame: Measured at Week 44 postpartum]

Incidence Rate of Combined Endpoint, Antepartum: Grade 3 or Higher AE Related to Treatment, or Discontinuation of Treatment Due to AE [Time Frame: Measured from study entry through end of pregnancy]

Incidence Rate, to 12 Weeks Postpartum, of Hepatotoxicity, Protocol-specific Definition, Related to Treatment [Time Frame: Measured from study entry through 12 weeks postpartum]

Number of Infants With Grade 3 or Higher Clinical or Laboratory AE Related to Treatment [Time Frame: Measured from study entry through Week 48 after birth]

Pharmacokinetic (PK) Parameter: Adjusted Mean of Area Under the Curve of Plasma Concentration Versus Time (AUC24h), for INH [Time Frame: Measured at antepartum (third trimester and >= 2 weeks after starting study drug) and week 16 postpartum (+/-) 4 weeks) while on active INH; blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dosing.]

Incidence Rate of Combined Endpoints: Infant TB or Infant Death [Time Frame: Measured from study entry through Week 48 after birth]

Number of Mothers With a Fetal Death [Time Frame: Measured from study entry through end of pregnancy]

Number of Mothers With a Low Birth-weight Infant [Time Frame: Measured on day of birth]

Incidence Rate, up to 12 Weeks Postpartum, of Grade 3 or Higher AE [Time Frame: Measured from study entry through 12 weeks postpartum]

Number of Infants With Tuberculosis Resistant to INH [Time Frame: Measured from study entry through Week 48 after birth]

Number of Mothers With an Infant Born Prematurely [Time Frame: Measured at delivery]

Pharmacokinetic (PK) Parameter: Adjusted Mean of Area Under the Curve (AUC24h), for EFV [Time Frame: Measured at antepartum (third trimester and >= 2 weeks after starting study drug) and week 16 postpartum (+/-) 4 weeks) while on active INH; blood samples were drawn pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dosing.]

Incidence Rate of Combined Endpoint, up to 12 Weeks Postpartum: Grade 3 or Higher AE Related to Treatment, or Discontinuation of Treatment Due to AE [Time Frame: Measured from study entry through 12 weeks after birth]

Incidence Rate of TB Infection Among Mothers [Time Frame: Measured from study entry to Week 48 after birth]

Incidence Rate, Antepartum, of Hepatotoxicity, Defined by DAIDS, Any Cause [Time Frame: Measured from study entry through delivery]

Number of Mothers With Tuberculosis Resistant to INH [Time Frame: Measured from study entry through Week 48 postpartum]

Number of Women by Level of Adherence to Prescribed Regimen, as Assessed by Pill Count [Time Frame: Adherence reported every 4 weeks during active treatment; study entry through week 28 for Arm A, week 12 postpartum through week 40 postpartum for Arm B]

Secondary ID(s)

10732

IMPAACT P1078

P1078

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 20/11/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01494038