HYDERABAD, INDIA – The National Institute of Allergy and Infectious Diseases is investing $70 million in a phase III clinical trial assessing the use of tuberculosis treatments in preventing multidrug-resistant tuberculosis infection among high-risk individuals, including infected household contacts of MDR-TB patients and people living with HIV, institute officials announced here.
The trial will compare the effectiveness of using delamanid – one of only three new MDR-TB drugs to be developed in half a century – with isoniazid, the standard TB drug used in treating latent TB infection, Dr. Peter Kim of the NIH said.
Household contacts of people with active TB disease are at increased risk of both latent infection and active TB disease. In high tuberculosis prevalence settings, child household contacts of TB patients are three to four times more likely to develop latent infection and five times more likely to develop active disease, while adults are two to three times more likely to have latent infection and three times more likely to have active disease, Dr. Rebecca Harris of the London School of Tropical Medicine and Hygiene presented here.
Household contacts in low TB prevalence settings have higher risk than those in low burden settings, she said.
Despite the “palpable excitement here about prevention advances,” Dr. Kim said, referring to this meeting’s focus on TB prevention and the announcements made here about advances in TB vaccine development and access to prevention drugs, “We still don’t know what we can do to prevent MDR-TB,” which infects nearly half a million people every year globally.
An effective measure to prevent becoming infected and sick with tuberculosis was not available for Manasi Khade, whose father was treated for MDR-TB in Mumbai, India – often referred to as the global epicenter of TB drug resistance. She became infected with extensively drug resistant TB at the age of 19.
Khade, who spoke here of her experience surviving XDR-TB – the most difficult-to-treat form of the disease – was one of the lucky few in India who had access to bedaquiline through a compassionate use program. Her father did not, and in the course of treatment lost sight in one eye and the ability to walk, even three years after being cured.
Researchers hypothesize that “prophylactic treatment with delaminid will prove better than isoniazid at reducing the likelihood that at-risk household members of individuals with MDR-TB will develop active TB disease,” NIH officials said.
The Protecting Households on Exposure to Newly Diagnosed Index Multidrug-Resistant TB Patients study – or PHOENIx MDR-TB study – is enrolling 5,610 participants, including 2,158 adults being treated for MDR-TB and 3,452 members of their households who are at high risk of developing active disease, Kim said. High-risk individuals include those who have latent TB infection, children under five, and those living with HIV or have immunosuppression from other conditions. Household members will be randomly assigned to receive either oral delamanid daily for 26 weeks or oral isoniazid plus vitamin B6 daily for 26 weeks.
The study is being conducted at 27 sites in 12 countries, including Brazil, Haiti, India, Kenya, Peru, South Africa and Thailand.
Delamanid’s manufacturer, Otsuka Pharmaceutical, is donating the drug for the trial, Dr. Kim said, raising questions from tuberculosis treatment advocates on whether the company intends to reduce the $1,700 cost for a six-month supply.