title: 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).
  
  
  METHODS
  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.affiliation: Division of Pulmonology, Department of Medicine, University of Cape Town Lung Institute, Cape Town, South Africa.
authors.forename: R
authors.initials: R
authors.lastname: Dawson
authors.affiliation: Division of Pulmonology, Department of Medicine, University of Cape Town Lung Institute, Cape Town, South Africa.
authors.forename: K
authors.initials: K
authors.lastname: Narunsky
authors.affiliation: Division of Pulmonology, Department of Medicine, University of Cape Town Lung Institute, Cape Town, South Africa.
authors.forename: D
authors.initials: D
authors.lastname: Carman
authors.affiliation: Clinical Trials Unit, Byramjee Jeejeebhoy Medical College, Pune, India.
authors.forename: N
authors.initials: N
authors.lastname: Gupte
authors.affiliation: Division of Medical Microbiology, Stellenbosch University, and National Health Laboratory Service, Cape Town, South Africa.
authors.forename: A
authors.initials: A
authors.lastname: Whitelaw
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: A
authors.initials: A
authors.lastname: Efron
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Barnes
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: J
authors.initials: J
authors.lastname: Hoffman
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Chaisson
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: H
authors.initials: H
authors.lastname: McIlleron
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Dorman
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011718:Pyrazinamide / Q000627:therapeutic use; D012293:Rifampin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D013019:South Africa; D013183:Sputum / Q000382:microbiology*; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin; C018421:rifapentine