Is four-month high-dose rifampicin regimen noninferior to the standard 6-month regimen for pulmonary tuberculosis?

"Efficacy results were closely in tune with that of the high-dose rifapentine-alone group of TBTC Study 31/A5349," the researchers wrote in the study.

Each year, an estimated 10 million people develop tuberculosis, which results in 1.4 million deaths worldwide. A cure is not always achieved in routine treatment that could be because patients may not adhere to the current 6-month regimen as recommended by the WHO (World Health Organization).

Reducing treatment to four months may improve adherence and increase cure rates and treatment completion. Reducing the treatment duration may also reduce the economic costs and inconvenience of treatment for patients.

Rifampicin is the cornerstone of current therapy owing to its ability to kill not only the Mycobacterium tuberculosis (MTB) undergoing rapid metabolism but also the persistent mycobacteria that results in most relapses.

Amina Jindani, Institute for Infection and Immunity, St. George’s, University of London, London, and colleagues aimed to evaluate the safety and efficacy of a higher rifampicin dose at either 1200 or 1800 mg/d in the RIFASHORT trial.

The goal was to accumulate evidence supporting its use for more rapid and secure sterilization of the lungs and a reduction in treatment duration to 4 months.

The researchers enrolled 672 patients from six countries who were given a diagnosis of rifampicin-susceptible pulmonary tuberculosis. They were randomly assigned to a 6-month control regimen (n=191), a similar 4-month regimen of rifampicin at 1200 mg/d (study regimen 1 [SR1]; n=192), or a 4-month regimen of rifampicin at 1800 mg/d (study regimen 2 [SR2]' n=195).

At regular intervals, sputum specimens were collected. The primary endpoint was calculated as a composite of treatment failure and relapse in patients who were sputum smear positive at baseline. The noninferiority margin was 8 percentage points. The non-inferiority of SR2 was tested first using a sequence of ordered hypotheses.

The authors reported the following findings:

• Noninferiority was not shown.
• Favourable response rates were 93, 90, and 87% in the control, SR1, and SR2 groups, respectively, for a country-adjusted absolute risk difference of 6.3 percentage points comparing SR2 with the control group.
• The proportions of participants experiencing a grade 3 or 4 adverse event were 4.0, 4.5, and 4.4% in the control, SR1, and SR2 groups, respectively.

"Four-month high-dose rifampicin regimens for the treatment of pulmonary tuberculosis did not have dose-limiting toxicities or side effects but did not meet noninferiority criteria compared with the standard 6-month control regimen," the researchers concluded.

Reference:

The study titled, "Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis," was published in the journal NEJM Evidence.