Two-stage activity-safety study of daily rifapentine during intensive phase treatment of pulmonary tuberculosis.

Abstract

BACKGROUND:

Rifapentine (RPT) has potent activity against Mycobacterium tuberculosis; however, the optimal dose for anti-tuberculosis treatment is unknown.

OBJECTIVE:

To determine the antimicrobial activity, safety and tolerability of RPT 450 mg or 600 mg administered daily during the first 8 weeks of treatment for pulmonary tuberculosis (TB).

DESIGN:

In a two-stage, randomised open-label study, adults with sputum smear-positive TB were randomised to receive RPT 450 mg, RPT 600 mg or rifampicin (RMP) 600 mg daily for 8 weeks with isoniazid, pyrazinamide and ethambutol. The primary endpoint was sputum culture status on Löwenstein-Jensen (LJ) medium at completion of 8 weeks of treatment.

RESULTS:

A total of 153 participants were enrolled. Both RPT regimens met pre-specified criteria to advance to stage 2. At completion of 8 weeks of treatment, LJ culture conversion occurred in 85% (35/41), 96% (43/45) and 94% (34/36) of participants in the RPT 450 mg, RPT 600 mg and RMP groups, respectively. The proportions of participants discontinuing treatment were similar (respectively 1/54 [2.0%], 1/51 [2.0%] and 4/48 [8.3%] in the RPT 450 mg, RPT 600 mg and RMP groups), as were ⩾grade 3 adverse events (0/54 [0%], 1/51 [2.0%] and 4/48 [8.3%]).

CONCLUSIONS:

There was a trend towards greater efficacy with RPT 600 mg than with RPT 450 mg. Daily RPT was safe and well-tolerated.

• Authors: R Dawson, K Narunsky, D Carman, N Gupte, A Whitelaw, A Efron, G L Barnes, J Hoffman, R E Chaisson, H McIlleron, S E Dorman
• Journal: The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease (Int J Tuberc Lung Dis) Vol. 19 Issue 7 Pg. 780-6 (Jul 2015) ISSN: 1815-7920 [Electronic] France
• PMID: 26056101 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antitubercular Agents
• Pyrazinamide
• Ethambutol
• Isoniazid
• Rifampin
• rifapentine

Topics

• Adult
• Antitubercular Agents (administration & dosage)
• Drug Administration Schedule
• Drug Therapy, Combination
• Ethambutol (therapeutic use)
• Female
• Humans
• Isoniazid (therapeutic use)
• Male
• Mycobacterium tuberculosis (drug effects)
• Pyrazinamide (therapeutic use)
• Rifampin (administration & dosage, adverse effects, analogs & derivatives)
• South Africa
• Sputum (microbiology)
• Treatment Outcome
• Tuberculosis, Pulmonary (drug therapy)
• Young Adult