Daily rifapentine for treatment of pulmonary tuberculosis: a randomized, dose-ranging trial

Published Date:

02/19/2015

Authors:

Dorman SE1, Savic RM, Goldberg S, Stout JE, Schluger N, Muzanyi G, Johnson JL, Nahid P, Hecker EJ, Heilig CM, Bozeman L, Feng PJ, Moro RN, Mac Kenzie W, Dooley KE, Nuermberger EL, Vernon A, Weiner M; the Tuberculosis Trials Consortium.

External link

Original Article

RATIONALE:

Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown.

OBJECTIVES:

We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment.

METHODS:

Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase.

MEASUREMENTS AND MAIN RESULTS:

A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration-time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively).

CONCLUSIONS:

Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629).

Events

«

November 2017

»
S
M
T
W
T
F
S
·
·
·
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
·
·

Projects

Modeling to improve TB decision-making in the...

We are part of a large consortium that is constructing epidemic and economic models of TB and HIV in collaboration with the U.S....

Read More

Comparative implementation and...

We are conducting a randomized comparative implementation trial across 56 sites in rural South Africa to evaluate three...

Read More

Understanding the impact of combined TB and...

We are developing models to understand the overlap of TB and HIV in three epidemiologically distinct settings (Canada, India,...

Read More

mHealth for improved TB contact investigation...

This multicenter randomized study is evaluating the implementation, effectiveness, cost-effectiveness, and population-level...

Read More

Population-level impact of isoniazid...

We are collaborating with a team that conducted a randomized trial of IPT in Khayelitsha, South Africa, to extend their findings...

Read More