HIV, Pregnant HIV Positive Women, Tuberculosis (TB)
Conditions
Keywords
pregnant women with HIV, pregnant women, hiv, tuberculosis, screening, tuberculosis preventive therapy
Brief summary
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.
Interventions
DIAGNOSTIC_TESTCRP screening (TB screening intervention arm)
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.
OTHERDeferred TPT (TPT delivery trial intervention arm)
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.
Sponsors
Makerere University
National Heart, Lung, and Blood Institute (NHLBI)
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
16 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of TB cases detected | Up to 6 months postpartum | 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 |
| Composite safety outcome | Up to 28 days postpartum | 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 |
| Composite effectiveness outcome | Up to 2-years after TPT initiation | The primary effectiveness outcome of the TPT delivery trial is a composite endpoint of maternal 2-year TB incidence and all-cause mortality. |
Countries
Uganda
Contacts
Primary ContactRachel Abbott, MPH
Outcome results
None listed