Long-Term Trial Data Boosts Case for Newer Drug-Resistant TB Regimens

2 October 2024

Extended follow-up on patients in a phase 3 clinical trial found that two bedaquiline-containing drug regimens for rifampicin-resistant tuberculosis (TB) maintained superiority compared with a 9-month injectable-based regimen at 132 weeks, researchers reported in the Lancet Respiratory Medicine.

The STREAM stage 2 trial randomized patients aged 15 years or older with rifampicin-resistant TB in seven countries to receive one of four treatments: the long regimen (the 20-month regimen recommended by the World Health Organization from 2011 to 2018), a control regimen (a 9-month regimen with the second-line injectable kanamycin), an oral regimen (9 months with bedaquiline replacing kanamycin), or a 6-month regimen (containing bedaquiline and supplemented with 8 weeks of kanamycin).

Initial analysis at 76 weeks showed that the oral regimen and the 6-month regimen were superior to the control regimen for the primary outcome of favorable status (negative cultures for Mycobacterium tuberculosis). The long-regimen arm of the trial was terminated early.

Effective and safe treatments for drug-resistant TB

In the follow-up analysis, investigators examined unfavorable status (death or a positive culture from one of two most recent samples) at week 132 in the three remaining groups. Among 517 patients in the modified intention-to-treat population, the proportion with unfavorable status was 19.6% in the oral regimen arm, 29.3% in the control regimen arm, and 9.8% in the 6-month regimen arm.

Few serious or severe adverse events were reported after week 76. Treatment-emergent hearing loss was recorded in significantly fewer participants on the oral regimen (3%) than the control regimen (8%), and there was no significant difference in severe hearing loss between the oral regimen and the 6-month regimen.

Death rates were low among participants allocated to the two bedaquiline-containing arms (1.01 per 100 person-years) compared with participants on the control regimen (1.52/1oo person-years).

“The findings of the STREAM stage 2 trial, combined with results of previous trials, show that shorter bedaquiline-containing regimens are an effective and safe treatment for patients with multidrug-resistant tuberculosis,” the investigators wrote. “These data confirm the value of the 9-month regimen recommended in current WHO guidelines and support the use of a 6-month regimen.”

By Chris Dall, MA

Source: CIDRAP