TB SCReening Improves Preventive Therapy Uptake in Pregnant Women With HIV

N/ANot Yet RecruitingNCT07278453

University of California, San Francisco1,500 enrolled

Overview

Because pregnant women have been excluded from clinical research, including tuberculosis (TB) research, little is known about diagnosing, treating and preventing TB in pregnant women. We plan to perform a two-stage randomized trial that will identify best practices for screening pregnant and postpartum women for active TB (screening by symptoms vs. C-reactive protein levels) and the optimal timing of TPT initiation, relative to pregnancy (immediately during pregnancy or deferred to postpartum). Because undiagnosed TB among pregnant women with HIV is associated with many devastating complications to both the mother and fetus, this research has the potential to improve maternal and birth outcomes worldwide.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SCREENING

Masking

DOUBLE

Enrollment

1,500

Conditions

Pregnant HIV Positive Women HIV Tuberculosis (TB)

Interventions

CRP screening (TB screening intervention arm)DIAGNOSTIC_TEST

In the TB screening trial, participants will be randomized to one of two WHO-recommended TB screening strategies: symptom-based TB screening (current practice) or CRP-based TB screening. Participants randomized to CRP-based screening will have CRP concentrations measured by study staff at the point-of-care, using blood obtained by finger prick. Participants randomized to the CRP arm with CRP ≥5 mg/L will be regarded as TB screen-positive. Participants randomized to the CRP arm with CRP \<5 mg/L will be regarded as TB screen-negative.

Deferred TPT (TPT delivery trial intervention arm)OTHER

In the TB preventive therapy (TPT) delivery trial, participants will be randomized to either immediate (antepartum) TPT (current recommendation) or deferred (postpartum) TPT, where TPT is deferred to 4 weeks postpartum. Participants randomized to deferred TPT will initiate TPT 4 weeks after delivery.

Eligibility

Sex: FEMALEMin age: 16 YearsHealthy volunteers:

Medical Language ↔ Plain English

For the TB screening trial, eligible patients include pregnant women with a viable singleton pregnancy by ultrasound, confirmed HIV infection, no current or planned TB treatment, no treatment with a drug with anti-mycobacterial activity within the past 2 weeks, no history of TB treatment or TPT within the past 2 years, lives within 20 km of the enrollment site, plans to deliver at the enrollment site, no plans to transfer antenatal care to a non-participating clinic, and no signs or symptoms of early or active labor. For the TPT delivery trial, eligible participants are participants in the TB screening trial who screened negative for TB by their randomization assignment, are eligible for TPT, are not taking any drug contraindicated for use with rifamycins, are not a contact with a TB case with known drug resistance to isoniazid or rifampin, are not heavy or binge alcohol consumers, do not have a history of liver disease, do not have liver enzymes ≥3-times the upper limit of normal.

Outcomes

Primary Outcomes

Proportion of TB cases detected

The primary outcome for the TB screening trial is the proportion of TB cases detected by baseline and repeated rounds of TB screening, up to 6-months postpartum

Time frame: Up to 6 months postpartum

Composite safety outcome

The primary safety outcome of the TPT delivery trial is the composite endpoint that includes spontaneous abortion, stillbirth, low birthweight, preterm birth and neonatal death

Time frame: Up to 28 days postpartum

Composite effectiveness outcome

The primary effectiveness outcome of the TPT delivery trial is a composite endpoint of maternal 2-year TB incidence and all-cause mortality.

Time frame: Up to 2-years after TPT initiation