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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/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)
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
Secondary ID [1] 0 0
MCT-44154
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Latent Tuberculosis Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse events of all grades - 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.
Timepoint [1] 0 0
Treatment duration
Secondary outcome [1] 0 0
Rates of drug completion (compliance) - 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.
Timepoint [1] 0 0
Treatment duration
Secondary outcome [2] 0 0
Confirmed active TB during 16 months after randomization (efficacy) - 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.
Timepoint [2] 0 0
16 months post-randomization
Secondary outcome [3] 0 0
Occurrence of drug resistance in confirmed cases of active TB - To describe the occurrence of drug-resistant, microbiologically confirmed active TB among children randomized to the two arms, during 16 months post-randomization.
Timepoint [3] 0 0
16 months post-randomization

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
Minimum age
No limit
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Woolcock Institute of Medical Research - Sydney
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
Benin
State/province [1] 0 0
Cotonou
Country [2] 0 0
Brazil
State/province [2] 0 0
Rio de Janeiro
Country [3] 0 0
Canada
State/province [3] 0 0
Alberta
Country [4] 0 0
Canada
State/province [4] 0 0
British Columbia
Country [5] 0 0
Canada
State/province [5] 0 0
Quebec
Country [6] 0 0
Ghana
State/province [6] 0 0
Kumasi
Country [7] 0 0
Guinea
State/province [7] 0 0
Africa
Country [8] 0 0
Indonesia
State/province [8] 0 0
West Java

Funding & Sponsors
Primary sponsor type
Other
Name
McGill University
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Canadian Institutes of Health Research (CIHR)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/show/NCT00170209
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Dick Menzies, MD, MSc
Address 0 0
McGill University Health Centre/Research Institute of the McGill University Health Centre
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications