Rifampin Versus Isoniazid for the Treatment of Latent Tuberculosis Infection in Children (P4v9)

• Status: Completed
• Trial end date: 2015-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Tuberculosis (TB) is spread by airborne transmission from adults with active contiguous TB to children, especially those living in the same household. Once children are exposed and infected they are at very high risk to develop active TB - which can be lethal if not detected and treated promptly. This makes it very important to detect TB infection as soon as possible, and treat this while it is still latent or dormant. Current therapy for latent TB infection is 9 months of Isoniazid; this is very effective if taken properly but because treatment is so long many children do not finish this. Four months of Rifampin is a recommended alternative. In adults this has been shown to be safer with much higher completion rates. However the effectiveness of this treatment is unclear, and is being studied in an ongoing study. The investigators plan to compare the safety as well as the acceptability and effectiveness of 4 months Rifampin with 9 months Isoniazid (standard treatment) in children in several sites in Canada and other countries.

It is hypothesized that among children at high risk for development of active TB, intolerance/adverse events will not be worse (non-inferiority), among those randomized to 4RIF compared to those randomized to 9INH. In addition completion of latent tuberculosis infection (LTBI) therapy will be significantly greater (superiority), and subsequent rates of active TB will not be significantly higher (non-inferiority) in children taking 4RIF.

• 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:

• Children (age <18) with documented positive TST (or in the absence of TST, a positive QFT or T-Spot) and prescribed 9INH for LTBI for the following indications:

1. HIV positive (TST >5 mm or QFT+)

2. Age 5 or less (TST >5 mm or QFT+)

3. Other reason for immuno-compromised state - such as therapy for malignancy or post-transplant (TST >5 mm or QFT+)

4. Contact: with adult or adolescent with active contagious pulmonary TB. (TST >5 mm or QFT +)

5. Have both of the following factors if TST = 10-14mm or QFT + or one factor if TST >15mm :

1. Arrival in Canada, Australia, or Saudi Arabia in the past 2 years from countries with estimated annual incidence of active TB greater than 100 per 100,000

2. Body mass index (BMI) less than 10th percentile for their age

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.

• Prior complete LTBI therapy or if children have taken >1 week and are still taking the treatment. Children will be eligible if they took an incomplete LTBI therapy (less than 80% of recommended total dose) but > 6 months ago.