PRISM-TB is an international, seamless, multicenter, open-label, randomized, controlled, pragmatic, stratified medicine, treatment shortening, multi-arm multi-stage (MAMS), noninferiority Phase 2/3 clinical trial for fluoroquinolone-susceptible multidrug-resistant/rifampin-resistant pulmonary tuberculosis (FQ-S MDR/RR-TB). In Stage 1, participants will be randomized among one of three treatment arms (one control and two experimental). Following the interim analysis (at the end of Stage 1) based on DOOR outcome comparisons and the entirety of the data, one of the four possible experimental strategies will be identified and continue into Stage 2. In Stage 2, participants will be randomized among one of two treatment arms (one control and one experimental).
The trial objective is to identify, among participants with fluoroquinolone-susceptible multidrug-resistant/rifampicin-resistant tuberculosis (FQ-S MDR/RR-TB), the preferred BPaLM strategy of 13 or 17 weeks for participants stratified to receive shorter treatment and 17 or 24 weeks for participants stratified to receive longer treatment, as defined by a prespecified stratification algorithm, and to evaluate whether this BPaLM strategy has noninferior efficacy to the control strategy at Week 73.
Who can participate
Age range
14 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Confirmed fluoroquinolone-susceptible rifampicin-resistant pulmonary tuberculosis, based on sputum Xpert MTB/RIF and Xpert MTB/XDR, and/or other validated molecular test, and/or phenotypic drug susceptibility testing.
. Aged ≥ 14 years.
. A verifiable address or residence location that is readily available for visiting, willingness to consent to home visits and phone calls, and willingness to inform the study team of any change of address during the treatment and follow-up period.
. Ability and willingness of individual to provide written informed consent or written consent from a parent, guardian, or caregiver and assent of the child participant per local ethics committee guidance.
. Documentation of negative HIV infection status within 30 days prior to study entry or documentation confirming HIV infection at any time before study entry.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Primary Efficacy Outcome: Desirability of Outcome Ranking (DOOR)
. For individuals with HIV: CD4+ cell count ≥ 50 cells/mm3 based on testing performed within 30 days prior to study entry.
. For individuals with HIV: Currently being treated with dolutegravir-based antiretroviral therapy (ART), or plan to initiate dolutegravir-based ART at or before study week 8.
. For individuals who are pregnant: at screening, evidence by ultrasound of a viable singleton pregnancy with an estimated gestational age at enrollment of ≥ 14 weeks as per screening ultrasound.
Exclusion criteria
. Known allergy/sensitivity, intolerance, or any hypersensitivity to components of study TB drugs or their formulation.
. One or more of the following laboratory parameters:
. Absolute neutrophil count (ANC) \< 1000/mm3.
. Hemoglobin level \< 8.0 g/dL.
. Serum or plasma alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times the upper limit of normal.
. Serum or plasma total bilirubin ≥ 3 times the upper limit of normal.
. Serum or plasma creatinine level ≥ 3 times the upper limit of normal.
. Evidence of laboratory values consistent with or equivalent to grade 4 toxicity (i.e., potentially life-threatening).