Rifampin Versus Isoniazid for the Treatment of Latent Tuberculosis Infection in Children (P4v9)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Trial to Compare Effectiveness of 4 Months Rifampin (4 RIF) With 9 Months Isoniazid (9 INH) in the Prevention of Active TB in Children: The P4v9 Trial|
- Adverse events of all grades [ Time Frame: Treatment duration ] [ Designated as safety issue: Yes ]The outcome of intolerability/adverse events (or the 'inverse' of safety) will include adverse events of all levels of severity (Grades 1 to 4) that resulted in permanent discontinuation of study drug, that were judged probably related to the study drug by a majority (2 out of 3) of the independent review panel members.
- Rates of drug completion (compliance) [ Time Frame: Treatment duration ] [ Designated as safety issue: No ]To compare the rates of study drug completion of all children randomized to 4RIF or 9INH. Completion will be defined as taking at least 80% of total planned doses within 23 weeks for 4RIF, or within 52 weeks for 9INH.
- Confirmed active TB during 16 months after randomization (efficacy) [ Time Frame: 16 months post-randomization ] [ Designated as safety issue: No ]To compare the rates of clinically diagnosed active TB as judged by an independent panel of pediatricians, up to 16 months post-randomization in children who complete study therapy per protocol.
- Occurrence of drug resistance in confirmed cases of active TB [ Time Frame: 16 months post-randomization ] [ Designated as safety issue: No ]To describe the occurrence of drug-resistant, microbiologically confirmed active TB among children randomized to the two arms, during 16 months post-randomization.
|Study Start Date:||August 2011|
|Estimated Study Completion Date:||March 2016|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Isoniazid
The standard therapy will be daily self-administered INH, 5 mg/kg/day (max=300mg/day) for 9 months (9INH). Dosage will be adjusted if weight is less than 42 kg at 200mg/day for 9 months.
The dosage of the medication is determined according to the weight of the child. The dose is once per day, 10-15 mg/kg/day (max=300mg/day). Total duration of treatment is 9 months. Both a detailed dose chart calculating doses by weight and age and protocols for preparation of medications (crushing pills, mixing suspensions) are available.
Active Comparator: Rifampin
The experimental arm will be daily self-administered RIF 10 mg/kg/day for 4 months (4RIF). Dosage will be adjusted if weight is 36-49 kg at 450 mg/day or at 300 mg/day for weight of 35 kg and less.
The dosage of the medication is determined according to the weight of the child. The dose is once per day, 10-20 mg/kg/day (max=600mg/day). Total duration of treatment is 4 months. Both a detailed dose chart calculating doses by weight and age and protocols for preparation of medications (crushing pills, mixing suspensions) are available.
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|Contact: Dick Menzies, MD, MSc||514-934-1934 ext firstname.lastname@example.org|
|Australia, New South Wales|
|Woolcock Institute of Medical Research||Recruiting|
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|Principal Investigator: Guy Marks, MD, PhD|
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|Contact: Richard Long, MD|
|Principal Investigator: Richard Long, MD|
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|Contact: Kevin Elwood, MD|
|Principal Investigator: Kevin Elwood, MD|
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|Montreal, Quebec, Canada, H2X 2P4|
|Contact: Dick Menzies, Dr (514) 934-1934 ext 32129 email@example.com|
|Principal Investigator: Dick Menzies, Dr|
|Sub-Investigator: David Zielinski, MD|
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|Principal Investigator: Joseph Obeng Baah|
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|Conakry, Africa, Guinea|
|Contact: Oumou Bah-Sow, MD|
|Principal Investigator: Oumou Bah-Sow, MD|
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|Contact: Rovina Ruslami, MD|
|Principal Investigator: Philip Hill, MD, MPH|
|Principal Investigator:||Dick Menzies, MD, MSc||McGill University Health Center|