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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT00170209
Registration number
NCT00170209
Ethics application status
Date submitted
12/09/2005
Date registered
15/09/2005
Date last updated
19/12/2017
Titles & IDs
Public title
Rifampin Versus Isoniazid for the Treatment of Latent Tuberculosis Infection in Children (P4v9)
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Scientific 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
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Secondary ID [1]
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MCT-44154
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Latent Tuberculosis Infection
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Condition category
Condition code
Infection
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Studies of infection and infectious agents
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Infection
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Other infectious diseases
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Respiratory
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Other respiratory disorders / diseases
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Isoniazid
Treatment: Drugs - Rifampin
Active Comparator: Isoniazid - The standard therapy will be daily self-administered INH, 10-15 mg/kg/day (max=300mg/day) for 9 months (9INH).
Active Comparator: Rifampin - The experimental arm will be daily self-administered RIF 10-20 mg/kg/day for 4 months (4RIF).
Treatment: Drugs: 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.
Treatment: Drugs: 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.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Adverse events of all grades
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Assessment method [1]
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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.
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Timepoint [1]
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Treatment duration
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Secondary outcome [1]
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Rates of drug completion (compliance)
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Assessment method [1]
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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.
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Timepoint [1]
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Treatment duration
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Secondary outcome [2]
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Confirmed active TB during 16 months after randomization (efficacy)
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Assessment method [2]
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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.
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Timepoint [2]
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16 months post-randomization
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Secondary outcome [3]
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Occurrence of drug resistance in confirmed cases of active TB
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Assessment method [3]
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To describe the occurrence of drug-resistant, microbiologically confirmed active TB among children randomized to the two arms, during 16 months post-randomization.
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Timepoint [3]
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16 months post-randomization
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Eligibility
Key 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:
1. HIV positive (TST >5 mm or QFT+)
2. Age 5 or less (TST >5 mm or QFT+)
3. Other reason for immuno-compromised state - such as therapy for malignancy or
post-transplant (TST >5 mm or QFT+)
4. Contact: with adult or adolescent with active contagious pulmonary TB. (TST >5 mm
or QFT +)
5. Have both of the following factors if TST = 10-14mm or QFT + or one factor if TST
>15mm :
1. 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
2. Body mass index (BMI) less than 10th percentile for their age
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Minimum age
No limit
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Maximum age
18
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/08/2011
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/05/2015
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Sample size
Target
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Accrual to date
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Final
844
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Recruitment in Australia
Recruitment state(s)
NSW
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Recruitment hospital [1]
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Woolcock Institute of Medical Research - Sydney
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Recruitment postcode(s) [1]
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- Sydney
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Recruitment outside Australia
Country [1]
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Benin
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State/province [1]
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Cotonou
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Country [2]
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Brazil
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State/province [2]
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Rio de Janeiro
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Country [3]
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Canada
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State/province [3]
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Alberta
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Country [4]
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Canada
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State/province [4]
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British Columbia
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Country [5]
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Canada
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State/province [5]
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Quebec
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Country [6]
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Ghana
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State/province [6]
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Kumasi
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Country [7]
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Guinea
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State/province [7]
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Africa
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Country [8]
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Indonesia
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State/province [8]
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West Java
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Funding & Sponsors
Primary sponsor type
Other
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Name
McGill University
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Address
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Country
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Other collaborator category [1]
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Other
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Name [1]
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Canadian Institutes of Health Research (CIHR)
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Address [1]
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Country [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT00170209
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Dick Menzies, MD, MSc
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Address
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McGill University Health Centre/Research Institute of the McGill University Health Centre
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Fax
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT00170209
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