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Randomized Clinical Trial of 4RIF vs. 9INH for the Treatment of Latent TB - Safety
This study is ongoing, but not recruiting participants.

First Received on September 12, 2005.   Last Updated on July 22, 2011   History of Changes
Sponsor: McGill University
Collaborator: Canadian Institutes of Health Research (CIHR)
Information provided by: McGill University
ClinicalTrials.gov Identifier: NCT00170209
  Purpose

Although effective medications to treat and even prevent Tuberculosis (TB) have been available for over 40 years, TB remains the most important infectious cause of mortality among adults in the world. One of the cornerstones of control of this disease is detection and treatment of infection - while it is still latent, or dormant. Nine months of Isoniazid (INH) is highly effective to treat latent infection, and so is considered the standard therapy. However, this therapy is often unsuccessful, because the long duration reduces completion rates, and increases cost, and it is associated with serious, even fatal side effects. An alternate regiment, of four months Rifampin has been recommended by authoritative agencies as an alternative, but there is surprisingly little data regarding the safety and efficacy of this regimen. We propose a randomized trial to compare the rate of adverse event resulting in permanent discontinuation of study drug, with 4 months of Rifampin or 9 months of Isoniazid given as daily, self-administered treatment for LTBI.


Condition Intervention Phase
Latent Tuberculosis Infection
Drug: Isoniazide (drug), Rifampin (drug)
Phase III

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 Completion and Tolerability of 4 Months Rifampin (4 Rif) and 9 Months Isoniazid (9 INH) in Treatment of Latent TB in Children:

Resource links provided by NLM:


Further study details as provided by McGill University:

Primary Outcome Measures:
  • Adverse events of all grades [ Time Frame: 3 years ] [ 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 independent review panel members.


Secondary Outcome Measures:
  • Completion of treatment, Active TB and Drug resistance [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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 independent review panel members.


Enrollment: 847
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)
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: Isoniazide (drug), Rifampin (drug)
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.
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: Isoniazide (drug), Rifampin (drug)
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Accept taking 9 months of Isoniazid for treatment of latent TB infection

Exclusion Criteria:

  • Less than 18 years old
  • contacts of INH resistant of index cases
  • HIV patients on triple therapy
  • drug interaction
  • inability to consent
  • adolescent taking birth control pill and do not accept to take other forms of contraception
  • allergy to the study drugs
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00170209

Locations
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
Guinea
Service de Pneumo-Phtisiologie, Hopital National Ignace Deen
Conakry, Africa, Guinea
Indonesia
Health Research Unit, Faculty of Medicine
Bandung, West Java, Indonesia
Saudi Arabia
King Fahad National Guard Hospital
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/Principal Investigator, McGill University / McGill University Health Center
ClinicalTrials.gov Identifier: NCT00170209     History of Changes
Other Study ID Numbers: MCT-44154
Study First Received: September 12, 2005
Last Updated: July 22, 2011
Health Authority: Canada: Health Canada

Keywords provided by McGill University:
Tuberculosis

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 February 12, 2012