Delamanid

THURSDAY, Feb. 6, 2025 -- Three all-oral shortened regimens have noninferior efficacy compared with standard therapy for fluoroquinolone-susceptible, rifampin -resistant tuberculosis , according to a study published in the Jan. 30 issue of the New England Journal of Medicine . Lorenzo Guglielmetti, M.D., Ph.D., from Médecins Sans Frontières in Paris, and colleagues conducted a phase 3, multinational, noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis to five nine-month oral regimens, including combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C), and pyrazinamide (Z). A total of 754 participants were randomly assigned to one of five combinations or standard therapy; 699 were included in the modified intention-to-treat analysis and 562 were included in the per-protocol analysis. The primary end point was a favorable outcome at week 73, defined by two negative sputum culture results or favorable bacteriologic, clinical, and radiologic evolution. The noninferiority margin was −12 percentage points. The researchers found that 80.7 percent of the patients in the standard-therapy group had favorable outcomes in the modified intention-to-treat analysis. In the modified intention-to-treat population, the risk difference between standard therapy and each of the four new regimens was noninferior: 9.8, 8.3, 4.6, and 2.5 percentage points for BCLLfxZ, BLMZ, BDLLfxZ, and DCMZ, respectively. In the per-protocol population, the differences were similar, apart from DCMZ, which was not noninferior. Across the regimens, the proportion of participants with grade 3 or higher adverse events was similar. "The results of this trial support the noninferior efficacy of three all-oral shortened regimens for the treatment of rifampin-resistant tuberculosis," the authors write. Two authors disclosed ties to the biopharmaceutical industry. Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

LOS ANGELES, Nov. 14, 2024 (GLOBE NEWSWIRE) -- ACTG, a global clinical trials network focused on HIV and other infectious diseases, announced two oral presentations on tuberculosis (TB) therapy that took place at The Union Conference on Lung Health 2024, in Bali, Indonesia. The oral presentation “Six Months is a Lot of Time to Lie:” Disclosure and Treatment Preferences Among Participants in a Tuberculosis Therapeutic Trial was presented by Faith Mugodhi, M.Sc., H.S.W., University of Zimbabwe-Clinical Trials Research Centre (UZ-CTRC). The oral presentation High Prevalence of Fluoroquinolone Resistance and katG Mutations in Adult Index Patients in a Multinational MDR-TB Prevention Trial was presented by Soyeon Kim, Sc.D., IMPAACT Senior Statistician, Frontier Science Foundation. “ACTG is honored to share these important findings with the many global stakeholders who are gathered in Indonesia at the Union Conference,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California, Los Angeles. “TB is one of ACTG’s key research priorities, as the disease remains a leading killer worldwide. The knowledge gained from the research presented today has the potential to inform our approach to TB treatment and ultimately improve the experiences of people with TB.” “Six Months is a Lot of Time to Lie:” Disclosure and Treatment Preferences Among Participants in a Tuberculosis Therapeutic Trial was a sub-study that investigated experiences around disclosure and treatment preferences among participants in ACTG 5362. Also known as CLO-FAST, this multi-center treatment-shortening trial for drug-susceptible TB randomized individuals to receive either a three-month regimen containing clofazimine (which can be associated with skin hyperpigmentation) or the six-month standard of care. The sub-study consisted of exploratory, qualitative in-depth interviews with 23 participants undergoing treatment in CLO-FAST from India, Malawi, and Zimbabwe. This presentation reported that all sub-study participants with TB had voluntarily disclosed their TB status to at least one other person. Nearly half of participants (43.5 percent) feared inadvertent disclosure of their status due to their treatment and attendance at the TB clinic; 80 percent (n=8) of these were taking clofazimine. One in five participants reported experiencing stigma or discrimination as a result of inadvertent disclosure, including being treated badly by their families or communities. Today’s presentation also found that participants had different preferences around the kind of treatment they received. Two-thirds (n=15) of participants reported that they would prefer the shortened regimen even if one of the medications led to a change in their skin color, while one-third (n=8) reported a preference for the longer regimen. That preference was associated with anticipation of stigma and beliefs that a longer regimen is more potent against TB. These data suggest that anticipated stigma and pre-existing beliefs may be important in understanding treatment preferences. High Prevalence of Fluoroquinolone Resistance and katG Mutations in Adult Index Patients in a Multinational MDR-TB Prevention Trial is an analysis from the PHOENIx study, an ongoing clinical trial evaluating the efficacy and safety of preventive treatment for multi-drug resistant TB (MDR-TB) with delamanid compared to isoniazid, conducted jointly by the ACTG and IMPAACT (International Maternal Pediatric Adolescent AIDS Clinical Trials) networks. (IMPAACT is a global collaboration of investigators, institutions, community representatives, and other partners, with a mission to improve health outcomes for infants, children, and adolescents as well as pregnant and postpartum people who are impacted by or living with HIV by evaluating novel treatments and interventions for HIV and its complications for tuberculosis and other related complications, through the conduct of high-quality clinical trials.) Knowledge of drug susceptibility in people with active TB is important for the provision of both efficacious treatment for their TB disease and TB preventive treatment for their contacts. This presentation sought to describe drug resistance patterns in adults with MDR-TB whose household members were approached to participate in PHOENIx. Between June 2019 and October 2023, 1,353 adults with documented MDR-TB were enrolled from 28 sites and 13 countries in Africa, Asia, and Central and South America. Among those for whom isoniazid mutation data were available, 73 percent (n=783 of 1078) had high-level resistance (katG mutations). Among the 699 participants who had fluoroquinolone drug-susceptibility testing available, 20 percent (n=139) had fluoroquinolone resistance. These results suggest that it is important to have non-fluoroquinolone options for TB preventive treatment. They also support the relevance of the PHOENIx trial’s evaluation of delamanid vs. isoniazid for TB preventive treatment in high-risk household contacts of adults with MDR-TB. Primary results of the clinical trial are anticipated in 2027. CLO-FAST is led by John Metcalfe, M.D., Ph.D., M.P.H., University of California San Francisco; Samuel Pierre, M.D., Les Centres Gheskio, Haiti; and Kimberly Scarsi, Pharm.D., M.S., University of Nebraska Medical Center and study drugs were supplied by the Global Drug Facility. PHOENIx is jointly conducted by ACTG and IMPAACT and led by Gavin Churchyard M.B.Ch.B., M.Med., Ph.D., The Aurum Institute NPC; Amita Gupta, M.D., M.H.S., Johns Hopkins University; Anneke Hesseling, M.B.Ch.B., M.Sc., Ph.D., Desmond Tutu TB Centre - Stellenbosch University; and Susan Swindells, M.B.B.S., University of Colorado. Delamanid is supplied for PHOENIx by Otsuka Pharmaceutical Company, Ltd. ACTG is led by Dr. Currier and Joseph J. Eron, M.D., University of North Carolina (ACTG Vice-Chair). The studies are sponsored by the National Institute of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID, which also funds ACTG) under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634. IMPAACT is also funded by NIAID with support and co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH). About ACTGACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at hundreds of locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve. Disclaimer: This content is solely the responsibility of ACTG and does not necessarily represent the official views of the NIH. Media Contact:Jenna Conley, ACTGjenna@conleycommunications.net