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Latent Tuberculosis Infection | Randomized Clinical Trial Comparing 4RIF vs. 9INH for LTBI Treatment-effectiveness

Latent Tuberculosis Infection research study

What is the primary objective of this study?

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.

Who is eligible to participate?

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.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Latent Tuberculosis Infection

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:IsoniazidThe dosage of the medication is determined according to the weight of the subject. The dose is once per day, in pill format, for a total daily dose of 300mg if subject weighs ≥ 42 kg, otherwise 200 mg. Total duration of treatment is for 9 months.

Drug:RifampinThe dosage of the medication is determined according to the weight of the subject. The dose is once per day, in pill format, for a total daily dose of 600 mg if the subject weighs ≥ 50 kg, 450 mg if the subject weighs ≥ 36 kg and < 50 kg, otherwise 300 mg for those weighing < 36 kg. Total duration of treatment is for 4 months.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

IsoniazidThe dosage of the medication is determined according to the weight of the subject. The dose is once per day, in pill format, for a total daily dose of 300mg if subject weighs ≥ 42 kg, otherwise 200 mg. Total duration of treatment is for 9 months.

RifampinThe dosage of the medication is determined according to the weight of the subject. The dose is once per day, in pill format, for a total daily dose of 600 mg if the subject weighs ≥ 50 kg, 450 mg if the subject weighs ≥ 36 kg and < 50 kg, otherwise 300 mg for those weighing < 36 kg. Total duration of treatment is for 4 months.

Study Status

Completed

Start Date: August 2009

Completed Date: April 2017

Phase: Phase 3

Type: Interventional

Design:

Primary Outcome: Confirmed active TB during 28 months after randomization

Secondary Outcome: Confirmed active TB in compliant participants

Study sponsors, principal investigator, and references

Principal Investigator: Dick Menzies, MD

Lead Sponsor: McGill University

Collaborator: Canadian Institutes of Health Research (CIHR)

More information:https://clinicaltrials.gov/show/NCT00931736

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