Rifapentine in High Doses in Pregnancy with TB (Radiant-Moms) study

Columbia University Health Sciences, New York NY

Investigators

Abstract

Modified Project Summary/Abstract Section The risk of tuberculosis (TB) is twice as high during and immediately after pregnancy than any other time in an adult’s life, and pregnant women with TB and HIV are at higher risk for mortality. More than 200,000 pregnant women develop TB annually, with the majority living in Africa and Asia. Pregnancy carries a high risk of adverse outcomes including miscarriage, preterm birth and increased risk of maternal to child HIV spread. Thus, optimizing care for pregnant and breastfeeding women (PBW) should be a global priority. However, PBW are routinely excluded from TB clinical trials and denied equal access to novel TB treatment options. In 2013, a panel of experts published a consensus statement for accelerated inclusion of PBW in TB clinical trials; in 2023, communities affected by TB called for inclusion of PBW in TB research. A new shorter TB treatment regimen is now recommended as an option for adults and adolescents globally; but not PBW. Potential access to this regimen will remain limited in PBW without the required data regarding dosing and safety for PBW and the developing fetus. There is a perception that the standard regimen is sufficient and safe, and PBW would not want to take a new regimen. However, no one has asked PBW or healthcare providers (HCP) in TB-endemic countries what guides their decisions to take or recommend treatment regimens in PBW. The Radiant-Moms study will use discrete choice experiment (DCE) to examine preferences among PBW and HCP regarding novel shorter TB treatment regimens during the pregnancy and postpartum periods. We will conduct the study in South Africa and the Philippines, representing different geographical settings with high TB burden and varying HIV prevalence. We will employ a two-phase mixed-methods design. In Phase I we will use qualitative methods to elicit input from stakeholders from the target populations: PBW, HCP, relevant informants, and community influencers from each country to determine optimal DCE survey design. We will also conduct in-depth qualitative cohort interviews in PBW with recent TB over time to gain an in-depth understanding of experiences during pregnancy and the postpartum period. In Phase II, we will conduct a quantitative survey among PBW and HCP, including preferences for attributes of TB treatment regimens and service delivery models (DCE). We will also identify barriers and facilitators to inclusion of PBW in TB trials. Radiant-Moms will generate evidence to support the evaluation, adoption, and safe practical implementation of new shorter TB treatment regimens during pregnancy and postpartum programmatically and provide global impetus and guidelines for their broader use with substantial benefits that shorter effective treatment may confer to PBW and their infants. Data from this study will help inform prioritization and implementation of future trials including safety and pharmacokinetic studies of new TB regimens in pregnancy and the postpartum period. Radiant-Moms will provide a model for the earlier and appropriate inclusion of PBW in clinical trials of novel TB treatments, for drug-susceptible and drug-resistant TB and prevention in the future.