Randomized Clinical Trial Comparing 4RIF vs. 9INH for LTBI Treatment-effectiveness
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ClinicalTrials.gov Identifier: NCT00931736 |
Recruitment Status :
Completed
First Posted : July 2, 2009
Last Update Posted : December 19, 2017
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Condition or disease | Intervention/treatment | Phase |
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Latent Tuberculosis Infection | Drug: Isoniazid Drug: Rifampin | Phase 3 |

Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 6031 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (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 |
Actual Study Start Date : | August 2009 |
Actual Primary Completion Date : | April 2017 |
Actual Study Completion Date : | April 2017 |

Arm | Intervention/treatment |
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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.
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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.
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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. |
- Confirmed active TB during 28 months after randomization [ Time Frame: 7 years total with data analysis ]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).
- Confirmed active TB in compliant participants [ Time Frame: 7 years total with data analysis ]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 ]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 ]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 ]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 ]Describe occurrence of drug resistance (to INH or RIF) among subjects who develop confirmed active TB.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00931736
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 |
Principal Investigator: | Dick Menzies, MD | McGill University / McGill University Health Centre |
Responsible Party: | Dr. Dick Menzies, Director of Respiratory Medicine, McGill University |
ClinicalTrials.gov Identifier: | NCT00931736 |
Other Study ID Numbers: |
MCT-94831 ISRCTN05675547 ( Other Grant/Funding Number: MCT-94831 ) |
First Posted: | July 2, 2009 Key Record Dates |
Last Update Posted: | December 19, 2017 |
Last Verified: | December 2017 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Tuberculosis |
Infections Tuberculosis Latent Tuberculosis Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Bacterial Infections and Mycoses Latent Infection Rifampin Isoniazid Antibiotics, Antitubercular Antitubercular Agents Anti-Bacterial Agents Anti-Infective Agents |
Leprostatic Agents Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Cytochrome P-450 CYP2B6 Inducers Cytochrome P-450 Enzyme Inducers Cytochrome P-450 CYP2C8 Inducers Cytochrome P-450 CYP2C19 Inducers Cytochrome P-450 CYP2C9 Inducers Cytochrome P-450 CYP3A Inducers Fatty Acid Synthesis Inhibitors Hypolipidemic Agents Antimetabolites Lipid Regulating Agents |