At least two authors independently screened and selected trials, assessed risk of bias, and extracted data. We sought clarifications from trial authors. We pooled relative risks (RRs) with their 95% confidence intervals (CIs), using a random-effects model if heterogeneity was significant. We assessed overall evidence quality using the GRADE approach.
MAIN RESULTS: Ten trials are included, enrolling 10,717 adults and children, mostly HIV-negative (2% HIV-positive), with a follow-up period ranging from two to five years.
Rifampicin (three/four months) vs. INH (six months)Five trials published between 1992 to 2012 compared these regimens, and one small 1992 trial in adults with
silicosis did not detect a difference in the occurrence of TB over five years of follow up (one trial, 312 participants; very low quality evidence). However, more people in these trials completed the shorter course (RR 1.19, 95% CI 1.01 to 1.30; five trials, 1768 participants; moderate quality evidence). Treatment-limiting adverse events were not significantly different (four trials, 1674 participants; very low quality evidence), but
rifampicin caused less hepatotoxicity (RR 0.12, 95% CI 0.05 to 0.30; four trials, 1674 participants; moderate quality evidence).
Rifampicin plus INH (three months) vs. INH (six months)The 1992
silicosis trial did not detect a difference between people receiving
rifampicin plus INH compared to INH alone for occurrence of active TB (one trial, 328 participants; very low quality evidence). Adherence was similar in this and a 1998 trial in people without
silicosis (two trials, 524 participants; high quality evidence). No difference was detected for treatment-limiting adverse events (two trials, 536 participants; low quality evidence), or hepatotoxicity (two trials, 536 participants; low quality evidence).
Rifampicin plus
pyrazinamide (two months) vs. INH (six months)Three small trials published in 1994, 2003, and 2005 compared these two regimens, and two reported a low occurrence of active TB, with no statistically significant differences between treatment regimens (two trials, 176 participants; very low quality evidence) though, apart from one child from the 1994 trial, these data on active TB were from the 2003 trial in adults with
silicosis. Adherence with both regimens was low with no statistically significant differences (four trials, 700 participants; very low quality evidence). However, people receiving
rifampicin plus
pyrazinamide had more treatment-limiting adverse events (RR 3.61, 95% CI 1.82 to 7.19; two trials, 368 participants; high quality evidence), and hepatotoxicity (RR 4.59, 95% 2.14 to 9.85; three trials, 540 participants; moderate quality evidence). Weekly, directly-observed
rifapentine plus INH (three months) vs. daily, self-administered INH (nine months)A large trial conducted from 2001 to 2008 among close contacts of TB in the USA, Canada, Brazil and Spain found directly observed weekly treatment to be non-inferior to nine months self-administered INH for the incidence of active TB (0.2% vs 0.4%, RR 0.44, 95% CI 0.18 to 1.07, one trial, 7731 participants; moderate quality evidence). The directly-observed, shorter regimen had higher treatment completion (82% vs 69%, RR 1.19, 95% CI 1.16 to 1.22, moderate quality evidence), and less hepatotoxicity (0.4% versus 2.4%; RR 0.16, 95% CI 0.10 to 0.27; high quality evidence), though treatment-limiting adverse events were more frequent (4.9% versus 3.7%; RR 1.32, 95% CI 1.07 to 1.64 moderate quality evidence)
AUTHORS' CONCLUSIONS: Trials to date of shortened prophylactic regimens using
rifampicin alone have not demonstrated higher rates of active TB when compared to longer regimens with INH. Treatment completion is probably higher and adverse events may be fewer with shorter
rifampicin regimens. Shortened regimens of
rifampicin with INH may offer no advantage over longer INH regimens.
Rifampicin combined with
pyrazinamide is associated with more adverse events. A weekly regimen of
rifapentine plus INH has higher completion rates, and less liver toxicity, though treatment discontinuation due to adverse events is probably more likely than with INH.