Randomized Clinical Trial Comparing 4RIF vs. 9INH for LTBI Treatment-effectiveness

• Status: Completed
• Trial end date: 2017-04-01
• Target enrollment: 0
• Participant gender: All

Summary

On a global scale, tuberculosis (TB) is the single most important infectious cause of morbidity and mortality. The World Health Organization has estimated that one-third of the entire world's population carries latent TB infection. A key TB control strategy is therapy of latent TB infection (LTBI). The current standard regimen is 9 months of Isoniazid (9INH). This regimen has excellent efficacy if taken regularly, but its effectiveness is substantially reduced by poor compliance. Serious side effects, such as hepato-toxicity can occur. Three shorter alternatives have been recommended: 6 months INH (6INH), 2 months Rifampin - Pyrazinamide (2RIF-PZA) and 4 months Rifampin (4RIF). The regimen of 6INH is less efficacious than 9INH, while 2RIF-PZA has been largely abandoned because of serious toxicity. Based on some evidence in treatment of LTBI, and extrapolating from extensive experience with treatment of active TB, it is believed that 4RIF has similar efficacy as 9INH. Therefore, the investigators are initiating the first multi-site international randomized trial that will compare the effectiveness of 4RIF and 9INH in preventing active tuberculosis.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: McGill University
• Collaborator: Canadian Institutes of Health Research (CIHR)
• Treatments: Isoniazid; Rifampin

Criteria

Inclusion Criteria:

• Adult (age 18 years and older) with documented positive TST (or in the absence of TST, a documented positive QFT) and prescribed 9 months of Isoniazid for LTBI, following authoritative recommendations.

Exclusion Criteria:

• Patients who were contacts of TB cases known to be resistant to Isoniazid, Rifampin, or both.

• Known HIV-infected individuals on anti-retroviral agents whose efficacy would be substantially reduced by Rifampin, unless therapy can safely be changed to agents not affected by Rifampin.

• Pregnant women - Rifampin and Isoniazid are considered safe in pregnancy but therapy is usually deferred until 2-3 months post-partum to avoid fetal risk and the potential for increased hepato-toxicity immediately post partum.

• Patients on any medication with clinically important drug interactions with Isoniazid or Rifampin, which their physician believes would make either arm contra-indicated.

• Patients with a history of allergy/hypersensitivity to Isoniazid or to Rifampin, Rifabutin or Rifapentine.

• Patients with active TB. Patients initially suspected to have active TB can be randomized once this has been excluded.

• Patients who have already started LTBI therapy.