Rifampin Versus Isoniazid for the Treatment of Latent Tuberculosis Infection in Children (P4v9)
This study is currently recruiting participants.
Verified August 2012 by McGill University
Sponsor:
McGill University
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Dr. Dick Menzies, McGill University
ClinicalTrials.gov Identifier:
NCT00170209
First received: September 12, 2005
Last updated: August 20, 2012
Last verified: August 2012
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Latent Tuberculosis Infection |
Drug: Isoniazid Drug: Rifampin |
Phase 3 |
| Study Type: | Interventional |
| 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 |
Resource links provided by NLM:
Further study details as provided by McGill University:
Primary Outcome Measures:
- 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.
Secondary Outcome Measures:
- 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.
| Estimated Enrollment: | 822 |
| 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) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Isoniazid
The standard therapy will be daily self-administered INH, 10-15 mg/kg/day for children (max=300mg/day) for 9 months (9INH). For children, dosing for both INH and RIF will be age and weight dependant, with highest doses for infants, and lowest for adolescents. A detailed dose chart - calculating doses by weight and age, and protocols for preparation of medications (crushing pills, mixing suspensions) will be prepared with expert input.
|
Drug: Isoniazid
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 children(max=600mg/day) for 4 months (4RIF). For children, dosing for both INH and RIF will be age and weight dependant, with highest doses for infants, and lowest for adolescents. A detailed dose chart - calculating doses by weight and age, and protocols for preparation of medications (crushing pills, mixing suspensions) will be prepared with expert input.
|
Drug: Rifampin
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.
|
Show Detailed Description Eligibility| Ages Eligible for Study: | up to 18 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
Children (age <18) with documented positive TST (or in the absence of TST, a positive QFT or T-Spot) and prescribed 9INH for LTBI for the following indications:
- HIV positive (TST >5 mm or QFT+)
- Age 5 or less (TST >5 mm or QFT+)
- Other reason for immuno-compromised state - such as therapy for malignancy or post-transplant (TST >5 mm or QFT+)
- Contact: with adult or adolescent with active contagious pulmonary TB. (TST >5 mm or QFT +)
Have both of the following factors if TST = 10-14mm or QFT + or one factor if TST >15mm :
- Arrival in Canada, Australia, or Saudi Arabia in the past 2 years from countries with estimated annual incidence of active TB greater than 100 per 100,000
- Body mass index (BMI) less than 10th percentile for their age
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.
- Prior complete LTBI therapy or if children have taken >1 week and are still taking the treatment. Children will be eligible if they took an incomplete LTBI therapy (less than 80% of recommended total dose) but > 6 months ago.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00170209
Contacts
| Contact: Dick Menzies, MD, MSc | 514-934-1934 ext 32129 | dick.menzies@mcgill.ca |
Locations
| Australia, New South Wales | |
| Woolcock Institute of Medical Research | Active, not recruiting |
| Sydney, New South Wales, Australia | |
| Benin | |
| Centre de Pneumophthysiologie | Recruiting |
| Cotonou, Benin | |
| Contact: Martin Gninafon, MD | |
| Principal Investigator: Martin Gninafon, MD | |
| Brazil | |
| 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 | |
| Canada, Alberta | |
| 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 | |
| Canada, Quebec | |
| Montreal Chest Institute | Recruiting |
| Montreal, Quebec, Canada, H2X 2P4 | |
| Contact: Dick Menzies, MD 514-934-1934 ext 32129 dick.menzies@mcgil.ca | |
| Contact: Karen Hornby, BScN MScEpi 514-934-1934 ext 32197 karen.hornby@mail.mcgill.ca | |
| Montreal Chest Institute | Recruiting |
| Montreal, Quebec, Canada, H2X 2P4 | |
| Contact: Dick Menzies, Dr (514) 934-1934 ext 32129 dick.menzies@mcgill.ca | |
| Principal Investigator: Dick Menzies, Dr | |
| Ghana | |
| Research and Development Unit, Komfo Anokye Teaching Hospital | Recruiting |
| Kumasi, Ghana | |
| Contact: Joseph Obeng Baah, MD | |
| Principal Investigator: Joseph Obeng Baah | |
| Guinea | |
| Service de Pneumo-Phtisiologie, Hopital National Ignace Deen | Recruiting |
| Conakry, Africa, Guinea | |
| Contact: Oumou Bah-Sow, MD | |
| Principal Investigator: Oumou Bah-Sow, MD | |
| Indonesia | |
| Health Research Unit, Faculty of Medicine | Recruiting |
| Bandung, West Java, Indonesia | |
| Contact: Rovina Ruslami, MD | |
| Principal Investigator: Philip Hill, MD, MPH | |
| Saudi Arabia | |
| King Fahad National Guard Hospital | Active, not recruiting |
| Riyadh, Saudi Arabia | |
Sponsors and Collaborators
McGill University
Canadian Institutes of Health Research (CIHR)
Investigators
| Principal Investigator: | Dick Menzies, MD, MSc | McGill University Health Center |
More Information
No publications provided by McGill University
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Dr. Dick Menzies, Director of Respiratory Medicine, McGill University |
| ClinicalTrials.gov Identifier: | NCT00170209 History of Changes |
| Other Study ID Numbers: | MCT-44154 |
| Study First Received: | September 12, 2005 |
| Last Updated: | August 20, 2012 |
| Health Authority: | Canada: Canadian Institutes of Health Research |
Keywords provided by McGill University:
|
Tuberculosis Children |
Additional relevant MeSH terms:
|
Tuberculosis Latent Tuberculosis Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Isoniazid Rifampin Fatty Acid Synthesis Inhibitors Hypolipidemic Agents Antimetabolites |
Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antitubercular Agents Anti-Bacterial Agents Anti-Infective Agents Therapeutic Uses Lipid Regulating Agents Antibiotics, Antitubercular Enzyme Inhibitors Leprostatic Agents Nucleic Acid Synthesis Inhibitors |
ClinicalTrials.gov processed this record on May 22, 2013