SMART4TB: Major Global Drug-Resistant TB Clinical Trial Launched
17 December 2025
Crucial treatment-shortening trial with potential to dramatically improve care for one of the most dangerous forms of TB begins enrollment in Mongolia.
The U.S. government-funded Supporting, Mobilizing, and Accelerating Research for Tuberculosis Elimination (SMART4TB) consortium is excited to announce that The Program for Rifampicin-Resistant Disease with Stratified Medicine for TB (PRISM-TB) trial, led by investigators from University of California, San Francisco, has launched at the National Center for Communicable Diseases in Ulaanbaatar, Mongolia with 10 participants enrolled. PRISM-TB (ClinicalTrials.gov NCT06441006) is one of three randomized, controlled trials aiming to optimize TB therapeutics and provide life-saving benefits for the millions suffering from the leading infectious disease killer in the world.
PRISM-TB is a two-stage trial that evaluates a stratified medicine approach to shortening drug-resistant TB treatment with bedaquiline, pretomanid, linezolid and moxifloxacin (BPaLM) to three or four months from a standard of six months. “PRISM-TB is an exciting opportunity to move away from a one-size-fits-all approach and evaluate a more personalized approach that we hope keeps people on treatment and helps them return to their lives faster,” said Bazarragchaa Tsogt, principal investigator for the trial at the National Center for Communicable Diseases.
It is estimated that 390,000 people develop drug-resistant TB each year; this form of TB does not respond to first-line treatments and consequently, is difficult and expensive to treat. Current standard treatments for drug-resistant TB are six to nine months; shorter treatment has the potential to make it easier for more people to complete treatment, to reduce the length of potentially difficult side effects, to ease burden on TB programs and to allow people return to healthy, productive lives faster.
PRISM-TB will enroll 200 participants, including adults, adolescents, pregnant and lactating women and people living with HIV, and randomize them into standard treatment, four months of BPaLM, or a stratified arm of three or six months of BPaLM, depending on individual risk factors.
The treatment stratification uses an algorithm based on factors demonstrated to be associated with TB outcomes like age, sex, HIV status, bacterial load in sputum and presence of cavitary lung disease to determine if a participant receives shorter or longer treatment.
“PRISM-TB will not only generate crucial data that we hope can inform guidelines and improve treatment in the U.S. and around the world, but we are employing a first-ever risk-benefit analysis with a desirability of outcome ranking at the end of Stage One to select the optimal treatment for Stage Two,” said Dr Gustavo Velásquez, PRISM-TB principal investigator and assistant professor of medicine in the Division of HIV, Infectious Diseases, and Global Medicine and the Center for Tuberculosis at University of California, San Francisco. “We believe these unique trial elements in addition to including priority populations such as adolescents and pregnant women will both optimize treatment and improve access.”
PRISM-TB trial drug donations include bedaquiline by Johnson & Johnson and pretomanid by Viatris/Mylan Pharmaceutical Private Limited. In addition to Mongolia, the PRISM-TB trial plans to open in clinical sites in Peru and Uganda soon. SMART4TB anticipates preliminary analysis in 2027.
The SMART4TB Consortium is made possible by the support of the U.S. Government through Cooperative Agreement 7200AA22CA00005. The contents are the sole responsibility of SMART4TB and do not necessarily reflect the views of the United States Government, consortium collaborators or members.
Source: SMART4TB
