BOSTON — A shorter treatment regimen consisting of rifapentine, moxifloxacin, isoniazid and pyrazinamide was more active than a control regimen against drug-susceptible pulmonary tuberculosis, researchers reported at the 2014 Conference on Retroviruses and Opportunistic Infections.
“Our interest is in trying to shorten the duration of treatment for active TB,” Susan Dorman, MD, associate professor of medicine in the division of infectious diseases at The Johns Hopkins University, said during her presentation. “Currently, treatment for drug-susceptible TB is 6 months long, and despite being efficacious and resulting in cure, it is long. Shorter treatments could potentially be associated with better adherence, less transmission and a lower likelihood of drug-resistant TB.”
The study took place in Rio de Janeiro, which Dorman said has a medium incidence of TB. The researchers randomly assigned adults with smear-positive pulmonary TB to the investigational regimen or a control regimen. The investigational regimen (PMHZ) included 7.5 mg/kg per day rifapentine (Priftin, Sanofi-Aventis), 400 mg per day moxifloxacin, plus isoniazid and pyrazinamide. The control regimen (REHZ) included 10 mg/kg per day rifampin, plus ethambutol, isoniazid and pyrazinamide. The patients received directly observed treatment 7 days a week for 8 weeks and sputum was collected weekly for culture.
Originally, the plan was to enroll 216 patients into the open-label superiority trial, Dorman said. However, the trial was stopped early because of slow enrollment and operational issues at the study site and drug procurement issues. The study included 121 patients.
Among the 62 patients in the PMHZ arm, nine (15%) discontinued treatment for any reason, as did eight of 59 patients (14%) in the REHZ arm. There was no difference in discontinuations due to toxicity. Dorman said 5% of the patients in the REHZ arm experienced liver toxicity, but no patients in the PMHZ arm did; however, 5% of the patients in the PMHZ arm experienced an allergic reaction.
In a modified intention-to-treat analysis, 51 patients (85%) in the PMHZ arm had a stable culture conversion on Löwenstein-Jensen solid medium at the end of the intensive phase, as did 44 (86%) of patients in the REHZ arm (P=.85). In liquid mycobacteria growth indicator tube (MGIT) medium, 39 patients (85%) in the PMHZ arm and 29 patients (69%) in the REHZ arm had stable culture conversion (P=.08).
A per-protocol analysis included patients who completed their treatment in 71 days or fewer and had an end-of-intensive phase culture. Thirty-six patients (94%) in the PMHZ arm and 27 patients (73%) in the REHZ arm had a stable culture conversion in MGIT medium (P=.01).
“Despite the trial being stopped early, there was a trend that favored the investigational arm,” Dorman said. “This is the first study in several decades that has swapped out and swapped in two drugs at the same time. Most of the recent TB studies have swapped one drug at a time, which is useful in understanding the contribution of individual drugs. Regardless, we prescribe regimens for TB, and it’s the potency of the regimen that is critical.”
Dorman said since the trial began, it became clear that the dose of rifapentine used was too low.
“This raises the possibility that the moxifloxacin, in combination with rifapentine, contributed much to the efficacy, resulting in activity that was good, despite the low dose of rifapentine,” she said.
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Conde M. #93. Presented at: CROI 2014; March 3-6, 2014; Boston.