R Dawson1, K Narunsky1, D Carman1, N Gupte2, A Whitelaw3, A Efron4, G L Barnes4, J Hoffman4, R E Chaisson4, H McIlleron5, S E Dorman4. 1. Division of Pulmonology, Department of Medicine, University of Cape Town Lung Institute, Cape Town, South Africa. 2. Clinical Trials Unit, Byramjee Jeejeebhoy Medical College, Pune, India. 3. Division of Medical Microbiology, Stellenbosch University, and National Health Laboratory Service, Cape Town, South Africa. 4. Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 5. Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
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.
RCT Entities:
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: Susan E Dorman; Radojka M Savic; Stefan Goldberg; Jason E Stout; Neil Schluger; Grace Muzanyi; John L Johnson; Payam Nahid; Emily J Hecker; Charles M Heilig; Lorna Bozeman; Pei-Jean I Feng; Ruth N Moro; William MacKenzie; Kelly E Dooley; Eric L Nuermberger; Andrew Vernon; Marc Weiner Journal: Am J Respir Crit Care Med Date: 2015-02-01 Impact factor: 21.405
Authors: Ian M Rosenthal; Ming Zhang; Kathy N Williams; Charles A Peloquin; Sandeep Tyagi; Andrew A Vernon; William R Bishai; Richard E Chaisson; Jacques H Grosset; Eric L Nuermberger Journal: PLoS Med Date: 2007-12 Impact factor: 11.069
Authors: Marcus B Conde; Fernanda C Q Mello; Rafael Silva Duarte; Solange C Cavalcante; Valeria Rolla; Margareth Dalcolmo; Carla Loredo; Betina Durovni; Derek T Armstrong; Anne Efron; Grace L Barnes; Mark A Marzinke; Radojka M Savic; Kelly E Dooley; Silvia Cohn; Lawrence H Moulton; Richard E Chaisson; Susan E Dorman Journal: PLoS One Date: 2016-05-09 Impact factor: 3.240
Authors: Jose Francis; Simbarashe P Zvada; Paolo Denti; Mark Hatherill; Salome Charalambous; Stanley Mungofa; Rodney Dawson; Susan Dorman; Nikhil Gupte; Lubbe Wiesner; Amina Jindani; Thomas S Harrison; Adeniyi Olagunju; Deirdre Egan; Andrew Owen; Helen M McIlleron Journal: Antimicrob Agents Chemother Date: 2019-03-27 Impact factor: 5.938
Authors: Claire J Calderwood; James P Wilson; Katherine L Fielding; Rebecca C Harris; Aaron S Karat; Raoul Mansukhani; Jane Falconer; Malin Bergstrom; Sarah M Johnson; Nicky McCreesh; Edward J M Monk; Jasantha Odayar; Peter J Scott; Sarah A Stokes; Hannah Theodorou; David A J Moore Journal: PLoS Med Date: 2021-04-26 Impact factor: 11.069
Authors: Patrick P J Phillips; Kelly E Dooley; Stephen H Gillespie; Norbert Heinrich; Jason E Stout; Payam Nahid; Andreas H Diacon; Rob E Aarnoutse; Gibson S Kibiki; Martin J Boeree; Michael Hoelscher Journal: BMC Med Date: 2016-03-23 Impact factor: 8.775