Randomized Clinical Trial Comparing 4RIF vs. 9INH for LTBI Treatment-effectiveness
This study is ongoing, but not recruiting participants.
Sponsor:
McGill University
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Dr. Dick Menzies, McGill University
ClinicalTrials.gov Identifier:
NCT00931736
First received: July 1, 2009
Last updated: January 22, 2015
Last verified: January 2015
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Latent Tuberculosis Infection |
Drug: Isoniazid Drug: Rifampin |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Randomized Clinical Trial of 4 Months of Rifampin vs. 9 Months of Isoniazid for Latent Tuberculosis Infection. Part 3 - Effectiveness |
Resource links provided by NLM:
Further study details as provided by McGill University:
Primary Outcome Measures:
- Confirmed active TB during 28 months after randomization [ Time Frame: 7 years total with data analysis ] [ Designated as safety issue: No ]Confirmed active TB during 28 months after randomization will be defined as a positive culture for M. tuberculosis, positive Nucleic acid amplification test for M TB complex, or caseating granulomas in a biopsy from any site. Positive AFB smears will be considered false positive if cultures are negative, but will be considered confirmatory, if cultures failed (for example if contamination or other technical problem occurs).
Secondary Outcome Measures:
- Confirmed active TB in compliant participants [ Time Frame: 7 years total with data analysis ] [ Designated as safety issue: No ]Compare the cumulative incidence of confirmed active TB among those who took at least 80% of doses of the LTBI treatment to which they were randomized, in less than 120% of the allowed time (i.e. efficacy ).
- Probable and confirmed active TB [ Time Frame: 7 years total with data analysis ] [ Designated as safety issue: No ]Compare the cumulative incidence of probable, as well as confirmed, active TB between patients randomized to the two regimens during 28 months following randomization.
- Rate of Grade 3 & 4 adverse events [ Time Frame: 7 years including data analysis ] [ Designated as safety issue: Yes ]Compare rates of Grades 3 &4 adverse events during treatment between subjects randomized to the two regimens.
- Comparative cost-effectiveness of regimens [ Time Frame: 7 years including data analysis ] [ Designated as safety issue: No ]Compare health system costs, and cost-effectiveness of the two regimens, in the different sites.
- Occurrence of drug resistance in confirmed cases of active TB [ Time Frame: 7 years including data analysis ] [ Designated as safety issue: No ]Describe occurrence of drug resistance (to INH or RIF) among subjects who develop confirmed active TB.
| Estimated Enrollment: | 5720 |
| Study Start Date: | August 2009 |
| Estimated Study Completion Date: | March 2016 |
| Estimated Primary Completion Date: | February 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Isoniazid
The 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: Isoniazid
The 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.
|
|
Active Comparator: Rifampin
The 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.
|
Drug: Rifampin
The 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.
|
Show Detailed Description
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00931736
Please refer to this study by its ClinicalTrials.gov identifier: NCT00931736
Locations
| Australia, New South Wales | |
| Woolcock Institute of Medical Research | |
| Sydney, New South Wales, Australia | |
| Benin | |
| Centre de Pneumophthysiologie | |
| Cotonou, Benin | |
| Brazil | |
| Universidade Gama Filho, Centro de Ciências Biológicas e da Saúde | |
| Rio de Janeiro, Brazil | |
| Canada, Alberta | |
| University of Alberta | |
| Edmonton, Alberta, Canada | |
| Canada, British Columbia | |
| British Columbia Centre for Disease Control | |
| Vancouver, British Columbia, Canada | |
| Canada, Quebec | |
| Montreal Chest Institute | |
| Montreal, Quebec, Canada, H2X 2P4 | |
| Canada, Saskatchewan | |
| Royal University Hospital | |
| Saskatoon, Saskatchewan, Canada | |
| Ghana | |
| Research and Development Unit, Komfo Anokye Teaching Hospital | |
| Kumasi, Ghana | |
| Guinea | |
| Service de Phtisiologie, Hopital National Ignace Deen | |
| Conakry, Guinea | |
| Indonesia | |
| Health Research Unit, Faculty of Medicine | |
| Bandung, West Java, Indonesia | |
| Korea, Republic of | |
| Korean Institute of Tuberculosis | |
| Seoul, Korea, Republic of | |
| Saudi Arabia | |
| King Fahad National Guard Hospital | |
| Riyadh, Saudi Arabia | |
Sponsors and Collaborators
McGill University
Canadian Institutes of Health Research (CIHR)
Investigators
| Principal Investigator: | Dick Menzies, MD | McGill University / McGill University Health Centre |
More Information
No publications provided
| Responsible Party: | Dr. Dick Menzies, Director of Respiratory Medicine, McGill University |
| ClinicalTrials.gov Identifier: | NCT00931736 History of Changes |
| Other Study ID Numbers: | MCT-94831, ISRCTN05675547 |
| Study First Received: | July 1, 2009 |
| Last Updated: | January 22, 2015 |
| Health Authority: | Canada: Health Canada |
Keywords provided by McGill University:
|
Tuberculosis |
Additional relevant MeSH terms:
|
Latent Tuberculosis Tuberculosis Actinomycetales Infections Bacterial Infections Gram-Positive Bacterial Infections Mycobacterium Infections Isoniazid Anti-Bacterial Agents Anti-Infective Agents |
Antimetabolites Antitubercular Agents Fatty Acid Synthesis Inhibitors Hypolipidemic Agents Lipid Regulating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses |
ClinicalTrials.gov processed this record on February 27, 2015