A Phase 4 interventional study of Isoniazid (INH) and Placebo for isoniazid (INH) in HIV Infections and Tuberculosis, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 13 sites in 8 countries. Open to female participants aged 13 Years and older. Per ClinicalTrials.gov, last updated 2021-11-05.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 4, Interventional, and Prevention
Tuberculosis (TB) is a leading cause of death among HIV-infected persons in low-income settings and can be a serious complication for HIV-infected pregnant women and their infants. Isoniazid (INH) preventive therapy (IPT) is effective in preventing TB infection in HIV-infected adults, but the safety of IPT in pregnant women is unknown. This study evaluated the safety of IPT among HIV-infected pregnant women.
TB disease is the most common HIV-related opportunistic infection and is a leading cause of death among HIV-infected persons in low-income settings. When TB occurs during or soon after pregnancy, it can cause complications for the mother as well as infant TB or death. Infant TB is very difficult to diagnose, and up to half of infant TB cases are caused by maternal TB. It has been shown that treatment for active TB is safe and effective during pregnancy and that IPT is safe and effective in preventing TB infection in HIV-infected adults. However, the safety of IPT in HIV-infected pregnant women is not known, especially in regard to its combination with highly active retroviral therapy (HAART). This study evaluated the safety of immediate (antepartum, or before delivery) versus deferred (postpartum, or after delivery) IPT among HIV-infected pregnant women in high TB incidence settings.
HIV-infected pregnant women were randomly assigned (1:1) to one of two arms: Arm A (immediate/antepartum INH) and Arm B (deferred/postpartum INH group). Women in both arms received oral prenatal multivitamins and pyridoxine (vitamin B6) once daily from study entry through Week 40 postpartum.
Study visits for women occurred at screening, entry, every 4 weeks until labor and delivery, at labor and delivery, and every 4 weeks after delivery until 48 weeks postpartum. Visits consisted of giving a medical history and undergoing a physical exam and blood collection; all visits through the delivery visit also included an obstetrical exam. Presence of HIV infection was documented at screening and a tuberculin skin test (TST) was administered at the delivery visit and at the Week 44 postpartum visit. Study visits for infants occurred at birth and at several time points through Week 48. These visits included a medical history, physical exam, and blood collection. Intensive pharmacokinetic (PK) samples, that is, samples taken at many different time points within a 24-hour test period, were collected from a small subset of women, one test period at antepartum and one at postpartum. Sparse PK samples, that is, samples taken at fewer time points within the test period, were collected on all women, once each at antepartum and postpartum.
4,734 studies on the registry are indexed under HIV Infections; 244 are open to participants now.
This study's enrollment of 956 is above the median of 80 across 3,489 interventional studies indexed under HIV Infections.
Browse HIV Infections studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
The following laboratory values obtained within 30 days prior to study entry:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Women in Arm A received immediate, or antepartum-initiated, INH treatment. Women received INH at study entry through Week 28, then switched to placebo for INH treatment through Week 40 postpartum.
Drug: Isoniazid (INH) · Drug: Placebo for isoniazid (INH)
Women in Arm B received deferred, or postpartum-initiated, INH treatment. Women received placebo for INH at study entry through Week 12 postpartum, then switched to INH through Week 40 postpartum.
Drug: Isoniazid (INH) · Drug: Placebo for isoniazid (INH)
300-mg tablet once daily by mouth, either from entry through Week 28 antepartum (Arm A) or from Week 12 postpartum through Week 40 postpartum (Arm B)
Placebo tablet once daily by mouth, either from Week 28 visit through Week 40 postpartum (Arm A) or from entry until Week 12 postpartum visit (Arm B)
Incidence Rate of Combined Endpoint: Grade 3 or Higher Adverse Events (AEs) Related to Treatment, or AE Causing Discontinuation of Treatment
Incidence rate, calculated by Mantel-Haenszel (MH), weighted by gestational age strata 1) gestational age at entry less than 24 weeks or 2) gestational age at entry greater than or equal to 24 weeks. AE's include laboratory results, signs/symptoms, or diagnoses; graded as per Division of AIDS (DAIDS) or by protocol-defined hepatotoxicity measures. Related to treatment indicates possibly, probably, or definitely related to INH or Placebo for INH as judged by Independent Endpoint Review Committee. Discontinuation refers to permanent discontinuation of study treatment.
Time frame: Measured from study entry through Week 48 after birth
Number of Mothers With a Fetal Death
Fetal deaths include both stillbirths and spontaneous abortions; in case of a multiple birth, mothers who had at least one fetal death
Time frame: Measured from study entry through end of pregnancy
Number of Mothers With a Fetus Small for Gestational Age
Small for gestational age was determined by physician at site
Time frame: Measured at delivery
Number of Mothers With an Infant Born Prematurely
Premature birth is defined as gestational age of \< 37 weeks at delivery.
Time frame: Measured at delivery
Number of Mothers With a Low Birth-weight Infant
Low birth weight is defined as weight \< 2500 mg
Time frame: Measured on day of birth
Number of Mothers With an Infant With a Congenital Anomaly
Includes congenital anomalies meeting the Metropolitan Atlanta Congenital Defects Program criteria.
Time frame: Measured from study entry through Week 48 after birth
Number of Mothers With an Adverse Pregnancy Outcome: Spontaneous Abortion, Stillbirth, Premature Birth, Low Birth Weight, or Congenital Anomaly
In case of a multiple birth, mothers who had at least one adverse pregnancy outcome. Spontaneous abortion is intra-uterine fetal death prior to 20 weeks of gestational age; stillbirth, the same, \>= 20 weeks; preterm delivery, \< 37 weeks of gestational age; low birth weight, \< 2,500 grams, and congenital anomalies meeting the Metropolitan Atlanta Congenital Defects Program criteria.
Time frame: Measured from study entry through Week 48 after birth
Number of Infants With Grade 3 or Higher Clinical or Laboratory AE
Laboratory, sign/symptom, or diagnoses graded as 3 or higher by DAIDS criteria.
Time frame: Measured from study entry through Week 48 after birth
Number of Infants With Grade 3 or Higher Clinical or Laboratory AE Related to Treatment
As before, but AE is judged to be possibly, probably, or definitely related to INH or Placebo for INH, by clinic medical staff
Time frame: Measured from study entry through Week 48 after birth
Number of Infants Which Are HIV-infected
HIV infection determined during follow-up period. Infection at birth or during breastfeeding
Time frame: Measured from study entry through study Week 44
Number of Infants Hospitalized
Hospitalization due to reasons other than birth
Time frame: Measured from study entry through Week 48 after birth
Incidence Rate of TB Infection Among Mothers
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. Probable or confirmed TB infection, as judged by Secondary Endpoint Review Committee
Time frame: Measured from study entry to Week 48 after birth
Incidence Rate of Tuberculosis (TB) Among Infants
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. Probable or confirmed TB, or congenital TB as defined using the Cantwell criteria (see reference), judged by the Secondary Endpoint Review Committee. Includes an infant death due to unknown cause.
Time frame: Measured from study entry through Week 48 after birth
Incidence Rate of Infant Death
Incidence rate was calculated by Mantel-Haenszel, weighted by gestational age strata.
Time frame: Measured from study entry through Week 48 after birth
Incidence Rate of Maternal Deaths
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
Time frame: Measured from study entry through Week 48 postpartum
Incidence Rate of Combined Endpoints: Maternal TB or Maternal Death
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
Time frame: Measured from study entry through Week 48 after birth
Incidence Rate of Combined Endpoints: Infant TB or Infant Death
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
Time frame: Measured from study entry through Week 48 after birth
Incidence Rate of Combined Endpoints: Maternal TB, Maternal Death, Infant TB, or Infant Death
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
Time frame: Measured from study entry through Week 48 after birth
Incidence Rate of Combined Endpoint, Antepartum: Grade 3 or Higher AE Related to Treatment, or Discontinuation of Treatment Due to AE
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata
Time frame: Measured from study entry through end of pregnancy
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
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
Time frame: Measured from study entry through 12 weeks after birth
Incidence Rate, Antepartum, of Grade 3 or Higher AE
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
Time frame: Measured from study entry through end of pregnancy
Incidence Rate, up to 12 Weeks Postpartum, of Grade 3 or Higher AE
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
Time frame: Measured from study entry through 12 weeks postpartum
Incidence Rate, Antepartum, of Hepatotoxicity, Defined by Protocol-specific Definition of Hepatotoxicity, Related to Treatment
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata. Protocol-specific definition of hepatotoxicity: Any one of the following: 1) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 5 times the upper limit of normal (ULN), where ULN is specified by the clinic physician; 2) Total bilirubin \> 3 X ULN; 3) ALT greater than 3 X ULN and total bilirubin greater than 2 X ULN; or 4) ALT \> 3 X ULN and persistent symptomatic clinical hepatitis
Time frame: Measured from study entry through delivery
Incidence Rate, to 12 Weeks Postpartum, of Hepatotoxicity, Protocol-specific Definition, Related to Treatment
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata
Time frame: Measured from study entry through 12 weeks postpartum
Incidence Rate, Antepartum, of Hepatotoxicity, Protocol-specific Definition, Any Cause
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
Time frame: Measured from study entry through delivery
Incidence Rate, to 12 Weeks Postpartum, of Hepatotoxicity, Protocol-specific Definition, Any Cause
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
Time frame: Measured from study entry through 12 weeks postpartum
Incidence Rate, Antepartum, of Hepatotoxicity, Defined by DAIDS, Related to Treatment
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. Hepatotoxicity definition as defined by DAIDS AE grading criteria 1.0.
Time frame: Measured from study entry through delivery
Incidence Rate, up to 12 Weeks Postpartum, of Hepatotoxicity, Defined by DAIDS, Related to Treatment
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata
Time frame: Measured from study start through 12 weeks postpartum
Incidence Rate, Antepartum, of Hepatotoxicity, Defined by DAIDS, Any Cause
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
Time frame: Measured from study entry through delivery
Incidence Rate, up to 12 Weeks Postpartum, of Hepatotoxicity, Defined by DAIDS, Any Cause
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
Time frame: Measured from study start through 12 weeks postpartum
Number of Mothers With Tuberculosis Resistant to INH
Resistance to INH from isolates of Mycobacterium tuberculosis, as a percentage of mothers who develop culture-confirmed TB
Time frame: Measured from study entry through Week 48 postpartum
Number of Infants With Tuberculosis Resistant to INH
Resistance to INH from isolates of Mycobacterium tuberculosis, as a percentage of infants who develop culture-confirmed TB
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
Pharmacokinetic parameter was estimated from population PK modeling fitted to the intensive PK data. AUC0-24h was predicted using population pharmacokinetic model using the NONMEM software program. A 2-compartment model with first-order absorption with transit compartment and first-order elimination with well-stirred liver model to capture hepatic clearance and first-pass extraction with 1 parameter (hepatic intrinsic clearance) was used,
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.
Pharmacokinetic (PK) Parameter: Adjusted Mean of Area Under the Curve (AUC24h), for EFV
Pharmacokinetic parameter was estimated from population PK modeling fitted to the intensive PK data. AUC0-24h was predicted using population pharmacokinetic model using the NONMEM software program. A 2-compartment model with first-order absorption with transit compartment and first-order elimination with well-stirred liver model to capture hepatic clearance and first-pass extraction with 1 parameter (hepatic intrinsic clearance) was used,
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.
Agreement Between Interferon-gamma Release Assay (IGRA) TB Test and Tuberculin Skin Test (TST) Results, Women at Delivery
IGRA done by Quantiferon Gold Test (QGIT). For women, TST is considered positive if greater than or equal to 5 mm
Time frame: Measured at delivery
Agreement Between IGRA and TST TB Test Results, Infant
The TST result was positive if greater than or equal to 10 mm in HIV-negative infants, or greater than or equal to 5 mm in HIV-positive infants.
Time frame: Measured at week 44 after birth
Agreement Between IGRA and TST TB Tests, Women at 44 Weeks Postpartum
IGRA done by Quantiferon Gold Test (QGIT). For women, TST is considered positive if greater than or equal to 5 mm
Time frame: Measured at Week 44 postpartum
Number of Women by Level of Adherence to Prescribed Regimen, as Assessed by Self-report
Adherence is the percentage of expected doses taken during the 28 week active treatment period, categorized as poor (\<60%), reasonable (\>= 60%, \<80%), good (\>=80%, \<90%), or excellent (\>= 90%). Measured by participant's self-report of doses taken within the last 3 days.
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
Number of Women by Level of Adherence to Prescribed Regimen, as Assessed by Pill Count
Adherence is the percentage of expected doses taken during the 28 week active treatment period. Pill count: participants returned their prescription pill containers, and the remaining (unused) pills were counted.
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
HIV-infected pregnant women and their infants, gestational age greater than 14 but less than 34 weeks, who reside in a high TB prevalence area. Recruited at participating medical clinics in those areas, a total of 13 sites in Haiti, India, Thailand, and in 5 countries in central and southern Africa. Recruitment from August 2014 to April 2016.
| Milestone | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Started | 477 | 479 |
| Completed | 389 | 396 |
| Not completed | 88 | 83 |
| Withdrew: Protocol violation | 1 | 1 |
| Withdrew: Lost to follow-up | 18 | 20 |
| Withdrew: Withdrawal by subject | 44 | 34 |
| Withdrew: Not able to get to clinic | 21 | 15 |
| Withdrew: Not willing to adhere to reqs | 2 | 9 |
| Withdrew: Death | 2 | 4 |
Incidence rate, calculated by Mantel-Haenszel (MH), weighted by gestational age strata 1) gestational age at entry less than 24 weeks or 2) gestational age at entry greater than or equal to 24 weeks. AE's include laboratory results, signs/symptoms, or diagnoses; graded as per Division of AIDS (DAIDS) or by protocol-defined hepatotoxicity measures. Related to treatment indicates possibly, probably, or definitely related to INH or Placebo for INH as judged by Independent Endpoint Review Committee. Discontinuation refers to permanent discontinuation of study treatment.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate of Combined Endpoint: Grade 3 or Higher Adverse Events (AEs) Related to Treatment, or AE Causing Discontinuation of Treatment | 15.03 | 14.93 |
Fetal deaths include both stillbirths and spontaneous abortions; in case of a multiple birth, mothers who had at least one fetal death
| Participants | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Number of Mothers With a Fetal Death | 17 | 9 |
Small for gestational age was determined by physician at site
No measurements were reported for this outcome.
Premature birth is defined as gestational age of \< 37 weeks at delivery.
| Participants | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Number of Mothers With an Infant Born Prematurely | 48 | 40 |
Low birth weight is defined as weight \< 2500 mg
| Participants | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Yes | 62 | 46 |
| No | 368 | 400 |
Includes congenital anomalies meeting the Metropolitan Atlanta Congenital Defects Program criteria.
| Participants | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Yes | 10 | 6 |
| No | 430 | 452 |
In case of a multiple birth, mothers who had at least one adverse pregnancy outcome. Spontaneous abortion is intra-uterine fetal death prior to 20 weeks of gestational age; stillbirth, the same, \>= 20 weeks; preterm delivery, \< 37 weeks of gestational age; low birth weight, \< 2,500 grams, and congenital anomalies meeting the Metropolitan Atlanta Congenital Defects Program criteria.
| Participants | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Yes | 106 | 78 |
| No | 343 | 382 |
Laboratory, sign/symptom, or diagnoses graded as 3 or higher by DAIDS criteria.
| Participants | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Number of Infants With Grade 3 or Higher Clinical or Laboratory AE | 193 | 196 |
As before, but AE is judged to be possibly, probably, or definitely related to INH or Placebo for INH, by clinic medical staff
| Participants | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Number of Infants With Grade 3 or Higher Clinical or Laboratory AE Related to Treatment | 5 | 6 |
HIV infection determined during follow-up period. Infection at birth or during breastfeeding
| Participants | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Yes | 3 | 7 |
| No | 436 | 451 |
| Unknown | 6 | 6 |
Hospitalization due to reasons other than birth
| Participants | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Number of Infants Hospitalized | 73 | 75 |
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. Probable or confirmed TB infection, as judged by Secondary Endpoint Review Committee
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate of TB Infection Among Mothers | 0.60 | 0.59 |
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. Probable or confirmed TB, or congenital TB as defined using the Cantwell criteria (see reference), judged by the Secondary Endpoint Review Committee. Includes an infant death due to unknown cause.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate of Tuberculosis (TB) Among Infants | 0.54 | 0.52 |
Incidence rate was calculated by Mantel-Haenszel, weighted by gestational age strata.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate of Infant Death | 2.99 | 4.42 |
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate of Maternal Deaths | 0.40 | 0.78 |
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate of Combined Endpoints: Maternal TB or Maternal Death | 1.00 | 1.38 |
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate of Combined Endpoints: Infant TB or Infant Death | 2.99 | 4.68 |
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate of Combined Endpoints: Maternal TB, Maternal Death, Infant TB, or Infant Death | 3.42 | 4.72 |
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate of Combined Endpoint, Antepartum: Grade 3 or Higher AE Related to Treatment, or Discontinuation of Treatment Due to AE | 15.93 | 13.79 |
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| 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 | 16.98 | 10.09 |
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate, Antepartum, of Grade 3 or Higher AE | 56.36 | 50.88 |
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate, up to 12 Weeks Postpartum, of Grade 3 or Higher AE | 56.48 | 40.59 |
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata. Protocol-specific definition of hepatotoxicity: Any one of the following: 1) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 5 times the upper limit of normal (ULN), where ULN is specified by the clinic physician; 2) Total bilirubin \> 3 X ULN; 3) ALT greater than 3 X ULN and total bilirubin greater than 2 X ULN; or 4) ALT \> 3 X ULN and persistent symptomatic clinical hepatitis
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate, Antepartum, of Hepatotoxicity, Defined by Protocol-specific Definition of Hepatotoxicity, Related to Treatment | 1.77 | 2.59 |
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate, to 12 Weeks Postpartum, of Hepatotoxicity, Protocol-specific Definition, Related to Treatment | 7.91 | 4.52 |
Incidence rate calculated by Mantel-Haenszel, weighted by gestational age strata.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate, Antepartum, of Hepatotoxicity, Protocol-specific Definition, Any Cause | 1.77 | 2.59 |
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate, to 12 Weeks Postpartum, of Hepatotoxicity, Protocol-specific Definition, Any Cause | 8.37 | 4.98 |
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata. Hepatotoxicity definition as defined by DAIDS AE grading criteria 1.0.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate, Antepartum, of Hepatotoxicity, Defined by DAIDS, Related to Treatment | 1.77 | 2.59 |
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate, up to 12 Weeks Postpartum, of Hepatotoxicity, Defined by DAIDS, Related to Treatment | 7.91 | 4.52 |
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate, Antepartum, of Hepatotoxicity, Defined by DAIDS, Any Cause | 1.77 | 2.59 |
Incidence rates calculated by Mantel-Haenszel, weighted by gestational age strata.
| events per 100 person-years | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Incidence Rate, up to 12 Weeks Postpartum, of Hepatotoxicity, Defined by DAIDS, Any Cause | 8.37 | 4.98 |
Resistance to INH from isolates of Mycobacterium tuberculosis, as a percentage of mothers who develop culture-confirmed TB
| Participants | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Number of Mothers With Tuberculosis Resistant to INH | 1 | 0 |
Resistance to INH from isolates of Mycobacterium tuberculosis, as a percentage of infants who develop culture-confirmed TB
No measurements were reported for this outcome.
Pharmacokinetic parameter was estimated from population PK modeling fitted to the intensive PK data. AUC0-24h was predicted using population pharmacokinetic model using the NONMEM software program. A 2-compartment model with first-order absorption with transit compartment and first-order elimination with well-stirred liver model to capture hepatic clearance and first-pass extraction with 1 parameter (hepatic intrinsic clearance) was used,
| hour*mg/L | Fast Metabolizers | Intermediate Metabolizers | Slow Metabolizers |
|---|---|---|---|
| Third trimester of pregnancy | 3.63 (2.88 to 4.88) | 6.55 (5.31 to 7.88) | 21.6 (18.5 to 26.0) |
| Week 16 postpartum | 4.25 (3.29 to 5.54) | 7.67 (6.49 to 9.18) | 25.3 (22.2 to 26.0) |
Pharmacokinetic parameter was estimated from population PK modeling fitted to the intensive PK data. AUC0-24h was predicted using population pharmacokinetic model using the NONMEM software program. A 2-compartment model with first-order absorption with transit compartment and first-order elimination with well-stirred liver model to capture hepatic clearance and first-pass extraction with 1 parameter (hepatic intrinsic clearance) was used,
| hour*mg/L | Fast Metabolizers | Intermediate Metabolizers | Slow Metabolizers |
|---|---|---|---|
| Third trimester of pregnancy | 38.5 (33.4 to 47.6) | 62.5 (51.4 to 94.9) | 153.02 (140.21 to 167) |
| Week 16 postpartum | 46.9 (42.1 to 59.7) | 76.2 (61.1 to 111) | 186 (166 to 210) |
IGRA done by Quantiferon Gold Test (QGIT). For women, TST is considered positive if greater than or equal to 5 mm
| Participants | Positive IGRA TB Test | Negative IGRA TB Test |
|---|---|---|
| Positive tuberculin skin test | 87 | 27 |
| Negative tuberculin skin test | 121 | 490 |
The TST result was positive if greater than or equal to 10 mm in HIV-negative infants, or greater than or equal to 5 mm in HIV-positive infants.
| Participants | Positive IGRA Test | Negative IGRA Tuberculin Test |
|---|---|---|
| Positive tuberculin skin test | 8 | 45 |
| Negative tuberculin skin test | 34 | 597 |
IGRA done by Quantiferon Gold Test (QGIT). For women, TST is considered positive if greater than or equal to 5 mm
| Participants | Positive IGRA TB Test | Negative IGRA TB Test |
|---|---|---|
| Positive tuberculin skin test | 100 | 20 |
| Negative tuberculin skin test | 127 | 459 |
Adherence is the percentage of expected doses taken during the 28 week active treatment period, categorized as poor (\<60%), reasonable (\>= 60%, \<80%), good (\>=80%, \<90%), or excellent (\>= 90%). Measured by participant's self-report of doses taken within the last 3 days.
| Participants | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Excellent adherence | 400 | 363 |
| Good adherence | 47 | 35 |
| Reasonable adherence | 15 | 8 |
| Poor adherence | 4 | 7 |
| Unknown | 11 | 66 |
Adherence is the percentage of expected doses taken during the 28 week active treatment period. Pill count: participants returned their prescription pill containers, and the remaining (unused) pills were counted.
| Participants | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) |
|---|---|---|
| Excellent adherence | 408 | 376 |
| Good adherence | 42 | 28 |
| Reasonable adherence | 8 | 6 |
| Poor adherence | 5 | 3 |
| Unknown | 14 | 66 |
Collected over From study entry to study completion at week 48 postpartum or premature study discontinuation. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Mother/Immediate INH | 2/477 (0.4%) | 71/477 (14.9%) | 438/477 (91.8%) |
| Mother/Deferred INH | 4/479 (0.8%) | 69/479 (14.4%) | 449/479 (93.7%) |
| Infant/Immediate INH | 11/445 (2.5%) | 86/445 (19.3%) | 417/445 (93.7%) |
| Infant/Deferred INH | 17/464 (3.7%) | 91/464 (19.6%) | 430/464 (92.7%) |
| Event | Mother/Immediate INH | Mother/Deferred INH | Infant/Immediate INH | Infant/Deferred INH |
|---|---|---|---|---|
| Sepsis neonatalInfections and infestations | 0/477 | 0/479 | 11/445 | 16/464 |
| Premature babyPregnancy, puerperium and perinatal conditions | 0/477 | 0/479 | 10/445 | 12/464 |
| Foetal deathPregnancy, puerperium and perinatal conditions | 12/477 | 9/479 | 0/445 | 0/464 |
| PneumoniaInfections and infestations | 0/477 | 1/479 | 8/445 | 10/464 |
| Pre-eclampsiaPregnancy, puerperium and perinatal conditions | 8/477 | 2/479 | 0/445 | 0/464 |
| Urinary tract infectionInfections and infestations | 7/477 | 5/479 | 0/445 | 0/464 |
| Meconium aspiration syndromeRespiratory, thoracic and mediastinal disorders | 0/477 | 0/479 | 6/445 | 3/464 |
| GastroenteritisInfections and infestations | 1/477 | 3/479 | 3/445 | 6/464 |
| Premature labourPregnancy, puerperium and perinatal conditions | 2/477 | 6/479 | 0/445 | 0/464 |
| Neonatal asphyxiaRespiratory, thoracic and mediastinal disorders | 0/477 | 0/479 | 5/445 | 3/464 |
| Event | Mother/Immediate INH | Mother/Deferred INH | Infant/Immediate INH | Infant/Deferred INH |
|---|---|---|---|---|
| Haemoglobin decreasedInvestigations | 199/477 | 191/479 | 353/445 | 365/464 |
| Neutrophil count decreasedInvestigations | 81/477 | 87/479 | 270/445 | 264/464 |
| Alanine aminotransferase increasedInvestigations | 187/477 | 206/479 | 31/445 | 31/464 |
| Aspartate aminotransferase increasedInvestigations | 141/477 | 151/479 | 9/445 | 2/464 |
| Blood glucose decreasedInvestigations | 144/477 | 128/479 | 1/445 | 1/464 |
| Neuropathy peripheralNervous system disorders | 94/477 | 109/479 | 0/445 | 0/464 |
| Weight decreasedInvestigations | 96/477 | 97/479 | 15/445 | 12/464 |
| CoughRespiratory, thoracic and mediastinal disorders | 46/477 | 35/479 | 66/445 | 87/464 |
| DiarrhoeaGastrointestinal disorders | 37/477 | 25/479 | 79/445 | 83/464 |
| GastroenteritisInfections and infestations | 25/477 | 20/479 | 58/445 | 50/464 |
All women in study.
| Age, Continuous(years) | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) | Total |
|---|---|---|---|
| Median | 29 (25 to 33) | 29 (24 to 33) | 29 (24 to 33) |
| Sex: Female, Male(Participants) | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) | Total |
|---|---|---|---|
| Female | 477 | 479 | 956 |
| Male | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 32 | 35 | 67 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 445 | 444 | 889 |
| White | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) | Total |
|---|---|---|---|
| Haiti | 8 | 15 | 23 |
| Botswana | 60 | 60 | 120 |
| Tanzania | 41 | 39 | 80 |
| South Africa | 91 | 91 | 182 |
| Uganda | 83 | 83 | 166 |
| Zimbabwe | 162 | 157 | 319 |
| Thailand | 15 | 18 | 33 |
| India | 17 | 16 | 33 |
| Gestational age at entry(Participants) | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) | Total |
|---|---|---|---|
| 14 - <24 weeks | 161 | 160 | 321 |
| 24 - 34 weeks | 316 | 319 | 635 |
| CD4 Count(Participants) | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) | Total |
|---|---|---|---|
| < 350 cells/mm^3 | 118 | 114 | 232 |
| 350 - <500 cells/mm^3 | 129 | 128 | 257 |
| 500 - <650 cells/mm^3 | 95 | 105 | 200 |
| >= 650 cells/mm^3 | 133 | 130 | 263 |
| Efavirenz-containing anti-retroviral (ARV) regimen(Participants) | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) | Total |
|---|---|---|---|
| No | 72 | 70 | 142 |
| Yes | 405 | 409 | 814 |
| Tuberculosis (TB) test result by Interferon-Gamma Release Assay (IGRA)(Participants) | Arm A (Immediate INH Treatment) | Arm B (Deferred INH Treatment) | Total |
|---|---|---|---|
| Positive | 139 | 144 | 283 |
| Negative | 301 | 297 | 598 |
| Indeterminate | 30 | 31 | 61 |
PDFs hosted by the registry, ClinicalTrials.gov.
This study is completed, as verified in Oct 2018. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Isoniazid
National Institute of Allergy and Infectious Diseases (NIAID) →