Randomized Clinical Trial Comparing 4RIF vs. 9INH for LTBI Treatment-effectiveness
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.
|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|
- 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).
- 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.
|Study Start Date:||August 2009|
|Estimated Study Completion Date:||March 2016|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
|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.
|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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|Contact: Dick Menzies, MD||(514) 934-1934 ext firstname.lastname@example.org|
|Contact: Karen Hornby, BScN MScEpi||(514) 934-1934 ext email@example.com|
|Australia, New South Wales|
|Woolcock Institute of Medical Research||Recruiting|
|Sydney, New South Wales, Australia|
|Contact: Guy Marks, MD, PhD|
|Principal Investigator: Guy Marks, MD, PhD|
|Centre de Pneumophthysiologie||Recruiting|
|Contact: Martin Gninafon, MD|
|Principal Investigator: Martin Gninafon, MD|
|Universidade Gama Filho, Centro de Ciências Biológicas e da Saúde||Recruiting|
|Rio de Janeiro, Brazil|
|Contact: Anete Trajman, MD, PhD|
|Principal Investigator: Anete Trajman, MD, PhD|
|University of Alberta||Recruiting|
|Edmonton, Alberta, Canada|
|Contact: Richard Long, MD|
|Principal Investigator: Richard Long, MD|
|Canada, British Columbia|
|British Columbia Centre for Disease Control||Recruiting|
|Vancouver, British Columbia, Canada|
|Contact: Kevin Elwood, MD|
|Principal Investigator: Kevin Elwood, MD|
|Montreal Chest Institute||Recruiting|
|Montreal, Quebec, Canada, H2X 2P4|
|Contact: Dick Menzies, Dr (514) 934-1934 ext 32129 firstname.lastname@example.org|
|Principal Investigator: Dick Menzies, MD|
|Royal University Hospital||Recruiting|
|Saskatoon, Saskatchewan, Canada|
|Contact: Vernon Hoeppner, MD|
|Principal Investigator: Vernon Hoeppner, MD|
|Research and Development Unit, Komfo Anokye Teaching Hospital||Recruiting|
|Contact: Joseph Obeng Baah, MD|
|Principal Investigator: Joseph Obeng Baah|
|Service de Phtisiologie, Hopital National Ignace Deen||Recruiting|
|Contact: Oumou Bah-Sow, MD|
|Principal Investigator: Oumou Sow-Bah, MD|
|Health Research Unit, Faculty of Medicine||Recruiting|
|Bandung, West Java, Indonesia|
|Contact: Rovina Ruslami, MD|
|Principal Investigator: Philip Hill, MD, MPH|
|Korea, Republic of|
|Korean Institute of Tuberculosis||Recruiting|
|Seoul, Korea, Republic of|
|Contact: HeeJin Kim, MD, MPH, PhD|
|Principal Investigator: HeeJin Kim, MD, MPH, PhD|
|King Fahad National Guard Hospital||Recruiting|
|Riyadh, Saudi Arabia|
|Contact: Hamdan Al-Jahdali, MD, PhD|
|Principal Investigator: Hamdan Al-Jahdali, MD, PhD|
|Principal Investigator:||Dick Menzies, MD||McGill University / McGill University Health Centre|