Rifampin Versus Isoniazid for the Treatment of Latent Tuberculosis Infection in Children (P4v9)
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|ClinicalTrials.gov Identifier: NCT00170209|
Recruitment Status : Completed
First Posted : September 15, 2005
Last Update Posted : December 19, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Latent Tuberculosis Infection||Drug: Isoniazid Drug: Rifampin||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||844 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||August 2011|
|Actual Primary Completion Date :||November 2014|
|Actual Study Completion Date :||May 2015|
Active Comparator: Isoniazid
The standard therapy will be daily self-administered INH, 10-15 mg/kg/day (max=300mg/day) for 9 months (9INH).
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 10-20 mg/kg/day for 4 months (4RIF).
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.
- Adverse events of all grades [ Time Frame: Treatment duration ]The outcome of intolerability/adverse events (or the 'inverse' of safety) will include adverse events of all levels of severity (Grades 1 to 5) 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 ]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 ]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 ]To describe the occurrence of drug-resistant, microbiologically confirmed active TB among children randomized to the two arms, during 16 months post-randomization.
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): NCT00170209
|Australia, New South Wales|
|Woolcock Institute of Medical Research|
|Sydney, New South Wales, Australia|
|Centre de Pneumophthysiologie|
|Universidade Gama Filho, Centro de Ciências Biológicas e da Saúde|
|Rio de Janeiro, Brazil|
|University of Alberta|
|Edmonton, Alberta, Canada|
|Canada, British Columbia|
|British Columbia Centre for Disease Control|
|Vancouver, British Columbia, Canada|
|Montreal Children's Hospital|
|Montreal, Quebec, Canada, H2X 2P4|
|Research and Development Unit, Komfo Anokye Teaching Hospital|
|Service de Pneumo-Phtisiologie, Hopital National Ignace Deen|
|Conakry, Africa, Guinea|
|Health Research Unit, Faculty of Medicine|
|Bandung, West Java, Indonesia|
|Principal Investigator:||Dick Menzies, MD, MSc||McGill University Health Centre/Research Institute of the McGill University Health Centre|