The Union hopes India would participate in STREAM trials for MDR-TB drugs

Aarti Dhar, CNS Correspondent, India
[First published in]
The International Union Against TB and Lung Disease (The Union) is hopeful that India would agree to participate in the second stage of the ambitious STREAM studies for the shortened multi-drug resistant TB(MDR-TB) regimen.

According to I.D. Rusen, Senior Vice President (Research and Development) at the Union, who leads the TREAT-TB Initiative and coordinates STREAM clinical studies for shortened MDR-TB regimens going on since 2010, the Union is in talks with the Indian government on the issue and is hopeful that India would agree to participate in future studies.

India has the largest burden of TB and MDR-TB in the world, and according to WHO’s Global TB Report 2015, there were an estimated 220,000 TB-related deaths in India in 2014 – marginally less than 240,000 deaths reported in 2013. The number of patients living with TB had also declined from 2.6 million in 2013 to 2.5 million in 2014. However, the number of new cases increased in the same period— from 2.1 million to 2.2 million. As per the report, there were 480,000 new MDR-TB cases in 2014 globally. Only a quarter of these cases are detected and treated, and of the reported MDR-TB patients treated only 50% are treated successfully. The current standard treatment regimen for MDR-TB lasts for up to 24 months, with the intensive phase requiring daily painful injections. This poses a significant burden both on patients and on the health systems, tasked with administering treatment that is fraught with severe side effects including hearing loss, depression and suicidal tendencies.

"The Union strongly believes that a more accessible and tolerable treatment for MDR-TB was urgently needed. Experience from a pilot programme in Bangladesh utilizing a 9 month treatment regimen demonstrated impressive outcomes," Dr Rusen adds. Results of the phase-1 study of the 9 month Bangladesh treatment regimen, which was a pilot, have shown an overall success rate of 87.9% with a cure rate of 82.5% and only 5.2% death rate. Updated trials on 515 patients showed a success rate of 84.5% with a cure rate of 82.1%. Further evaluation was conducted on 1,000 patients in 9 West African countries (Benin, Burkina Faso, Burudi, Cameroon, Central African Republic, Cote d’Ivoire, Democratic Republic of Congo, Niger and Rwanda) on a modified Bangladesh regimen. An interim analysis of 408 patients in this evaluation demonstrated a success rate of 82.1%. STREAM study is among the ambitious randomized controlled studies going on at present. In STREAM stage -1, the Bangladesh regimen is compared to the locally used WHO regimen in the participating countries.

Stage-1 study sites for STREAM were Addis Ababa in Ethiopia, Ulan Bator in Mongolia, Ho Chi Minh in Vietnam and Sizwe, Durban and Pietermartizburg in South Africa.  So far, 424 patients have been enrolled for the study and the final patient follow-up will be done in the last quarter of 2017 and the results are expected in early 2018. After extensive discussions between the study team, the local investigators and other experts it was agreed that additional regimens, comprising a fully oral 9-month regimen and a 6-month simplified regimen, would also be be evaluated. Both of these include the latest TB drug—bedaquiline.

The first patient was enrolled for STREAM Stage-2 in March this year and so far 10 patients have been enrolled. The number of patients will be 1155 and the recruitment will be completed by middle of 2018. The first patient follow-up is scheduled for early 2021 and the initial end point results are expected to come by the middle of 2030. The project is funded by USAID, DFID, MRC, AFD and bedaquiline provided by Janssen Pharmaceuticals— developers of the new drug.

[First published in]

Aarti Dhar, Citizen News Service - CNS
June 29, 2016