A large clinical trial to assess treatments for preventing people at high risk from developing multidrug-resistant tuberculosis (MDR-TB) has begun. The study is comparing the safety and efficacy of a new MDR-TB drug, delamanid, with the decades-old TB drug isoniazid for preventing active MDR-TB disease in children, adolescents, and adults at high risk who are exposed to adult household members with MDR-TB. Study participants are at high risk for MDR-TB because they either have latent TB infection, immune systems suppressed by HIV or other factors, or are younger than age 5 years and therefore have a weak immune system.
Most household members of people with MDR-TB are likely to acquire latent TB infection, in which the bacterium Mycobacterium tuberculosis lives in the body without making a person sick. Without adequate preventive care, many of these individuals will progress to active MDR-TB disease, in which the bacteria become active and multiply. An estimated 460,000 people globally developed MDR-TB in 2017, according to the World Health Organization.
Existing treatments for MDR-TB are often highly toxic and poorly tolerated, placing patients at high risk of disability and death and curing them only about half the time. Treatment options are limited, and expensive, and recommended medicines are not always available. Moreover, TB kills more people each year than any other infectious disease. For all these reasons, it is essential to prevent latent TB infection from progressing to active MDR-TB disease.
Delamanid is one of the first drugs available specifically to treat people with MDR-TB and the first to exist in a formulation suitable for children. The study investigators hypothesize that prophylactic treatment with delamanid will prove better than isoniazid at reducing the likelihood that at-risk household members of individuals with MDR-TB will develop active TB disease. Isoniazid is the standard drug for TB prevention in many of the study’s host countries.
The Phase 3 clinical trial is called PHOENIx MDR-TB, short for Protecting Households on Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients. The study is co-funded by NIAID and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, also part of NIH. The AIDS Clinical Trials Group (ACTG) and the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network, both funded by NIH, are conducting the PHOENIx MDR-TB study. The manufacturer of delamanid, Otsuka Pharmaceutical Co., Ltd. of Tokyo, is donating the drug to the trial.
The PHOENIx MDR-TB study will take place at more than 27 sites in at least 12 countries, including Botswana, Brazil, Haiti, India, Kenya, Peru, the Philippines, South Africa, Tanzania, Thailand, Uganda, and Zimbabwe. The study team will enroll approximately 5,610 participants, including 2,158 adults ages 18 and older who are being treated for confirmed active MDR-TB through their country’s national TB treatment program and 3,452 members of their households who are at high risk for developing active TB disease. The participating household members will be assigned at random to receive either oral delamanid daily for 26 weeks or oral isoniazid plus vitamin B6 daily for 26 weeks. All at-risk members of the same household will receive the same drug regimen.