title: Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis: study 29 of the tuberculosis trials consortium.
abstract: BACKGROUND
  Rifapentine administered 5 days per week has potent activity in mouse models of antituberculosis chemotherapy, but efficacy and safety data are limited in humans. We compared the antimicrobial activity and safety of rifapentine vs rifampin during the first 8 weeks of pulmonary tuberculosis treatment.
  
  
  METHODS
  In total, 531 adults with sputum smear-positive pulmonary tuberculosis were randomized to rifapentine 10 mg/kg/dose or rifampin 10 mg/kg/dose, administered 5 days per week for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. Coprimary outcomes were negative sputum culture on liquid and on solid media at completion of intensive phase.
  
  
  RESULTS
  Negative cultures on solid media occurred in 145 of 174 participants (83.3%) in the rifampin group and 171 of 198 participants (86.4%) in the rifapentine group (difference, 3.0%; 95% confidence interval [CI]: -4.3, 10.5); negative cultures in liquid media occurred in 110 of 169 (65.1%) in the rifampin group and 133 of 196 (67.9%) in the rifapentine group (difference, 2.8%; 95% CI: -6.9, 12.4). Among 529 participants who received study therapy, 40 of 254 participants (15.7%) in the rifampin group and 40 of 275 participants (14.5%) in the rifapentine group prematurely discontinued treatment (P=.79).
  
  
  CONCLUSIONS
  The rifapentine regimen was safe but not significantly more active than a standard rifampin regimen, by the surrogate endpoint of culture status at completion of intensive phase. Assessment of higher exposures to rifapentine for tuberculosis treatment is warranted.
  
  
  BACKGROUND
  NCT00694629.
authors: Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. dsusan1@jhmi.edu
authors: Susan E
authors: SE
authors: Dorman
authors: Stefan
authors: S
authors: Goldberg
authors: Jason E
authors: JE
authors: Stout
authors: Grace
authors: G
authors: Muzanyi
authors: John L
authors: JL
authors: Johnson
authors: Marc
authors: M
authors: Weiner
authors: Lorna
authors: L
authors: Bozeman
authors: Charles M
authors: CM
authors: Heilig
authors: Pei-Jean
authors: PJ
authors: Feng
authors: Ruth
authors: R
authors: Moro
authors: Masahiro
authors: M
authors: Narita
authors: Payam
authors: P
authors: Nahid
authors: Susan
authors: S
authors: Ray
authors: Edward
authors: E
authors: Bates
authors: Betial
authors: B
authors: Haile
authors: Eric L
authors: EL
authors: Nuermberger
authors: Andrew
authors: A
authors: Vernon
authors: Neil W
authors: NW
authors: Schluger
mesh_terms: D000328:Adult; D000904:Antibiotics, Antitubercular / Q000009:adverse effects / Q000627:therapeutic use*; D057915:Drug Substitution; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D012293:Rifampin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000904:Antibiotics, Antitubercular; D012293:Rifampin; C018421:rifapentine