Short-course TB therapy fails in three international trials

The primary efficacy endpoint, the percentage of patients with an unfavorable outcome after 24 months, was 17.2% in the control group and 21.0% in the experimental group, a significant difference. In particular, more than twice as many patients in the experimental group (14.6%) had a relapse than in the control group (7.1%). As with Dr. Gillespie’s study, Dr. Merle’s study failed to show that the short-course regimen was noninferior to the standard regimen. Again, “the expectations raised by [phase I and II trials] were not borne out in this phase III trial,” they said (N. Engl. J. Med. 2014 Oct. 23 [doi:10.1056/NEJMoa1315817]).

The third trial, involving 827 patients in South Africa, Zimbabwe, Botswana, and Zambia, compared the standard control regimen against a 4-month regimen in which isoniazid was replaced by moxifloxacin and a 6-month regimen in which isoniazid was replaced by moxifloxacin, said Dr. Amina Jindani of St. George’s University of London and University College London and her associates.

In the per-protocol analysis, unfavorable outcomes occurred in 4.9% of the control group and 3.2% of the 6-month experimental group, compared with 18.2% of the short-course experimental group. The corresponding figures for the intention-to-treat analysis were 14.4%, 13.7%, and 26.9%, respectively.

Again, this discrepancy was attributed primarily to the significantly higher relapse rate in the short-course, compared with the control treatments – 26 cases with 4 months of treatment vs. 5 cases each with 6 months, Dr. Jindani and her associates said (N. Engl. J. Med. 2014 Oct. 23 [doi:10.1056/NEJMoa1314210]).