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Study Evaluates Delamanid as Prevention for People Exposed to MDR-TB

PHOENIx MDR-TB is comparing the safety and efficacy of delamanid, a new drug, with the older TB drug isoniazid for preventing active MDR-TB among individuals exposed to the disease.

Most household members of people with multidrug-resistant tuberculosis (MDR-TB) are likely to acquire latent TB infection. Without adequate preventive care, many of these individuals will develop active MDR-TB disease, in which the bacteria become active and multiply.

According to the World Health Organization, an estimated 460,000 people developed MDR-TB in 2017 worldwide. Existing treatments for MDR-TB are often highly toxic and poorly tolerated, placing patients at high risk for disability and death and curing them only about half the time.

TB kills more people each year than any other infectious disease; therefore, it is essential to prevent latent TB infection from progressing to active MDR-TB disease.

In order to assess treatments for preventing at-risk individuals from developing MDR-TB, the National Institutes of Health (NIH) has launched a new large clinical trial. The phase 3 study is called PHOENIx MDR-TB (Protecting Households on Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients).

The study will enroll approximately 5610 participants who are at high risk for acquiring MDR-TB because they either have an existing latent TB infection, their immune systems are suppressed by HIV or other factors, or they are younger than 5 years of age and therefore have weak immune systems.

The trial is comparing the safety and efficacy of delamanid, a new drug, with the older TB drug isoniazid. Delamanid is 1 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 delamanid will reduce the likelihood that at-risk household members of individuals with MDR-TB will develop active TB disease better than isoniazid.

More than 27 sites in at least 27 countries will enroll participants into the study. Of the 5610 participants, 2158 adults 18 years and older who are being treated for confirmed active MDR-TB through a national TB treatment program will be enrolled along with 3452 members of their households who are at an increased risk for developing active TB.

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. If multiple members of 1 household are enrolled they will all receive the same regimen.

As part of the observation, the household contacts will visit the clinic every 2 to 12 weeks to undergo a physical exam and other health assessments. The participants will be followed for 96 weeks to determine whether the regimen is successful in preventing active TB disease.

“We urgently need to halt the spread of MDR-TB,” Gavin Churchyard, MBBCh, MMed, PhD, founder and chief executive officer of the Aurum Institute for Health Research in Johannesburg, and a lead investigator on the study, said in the NIH’s statement. “Preventing latent MDR-TB from progressing to active disease protects the health of the individual while reducing the transmission of drug-resistant Mycobacterium tuberculosis.”

Final results from the trial are expected in 2024.

The study is co-funded by the National Institute of Allergy and Infectious Diseases, which is part of the NIH, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The trial is being conducted by the AIDS Clinical Trials Group and the International Maternal Pediatric Adolescent Aids Clinical Trials Network. The manufacturer of delamanid, Otsuka Pharmaceutical Co., Ltd. Of Tokyo is donating the drug for the trial.