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Trial registered on ANZCTR


Registration number
ACTRN12613000599774
Ethics application status
Approved
Date submitted
9/05/2013
Date registered
27/05/2013
Date last updated
12/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Short-course Isoniazid and Rifapentine for Cost-effective Latent tuberculosis Eradication
Scientific title
Randomised controlled trial for cost-benefit of short-course isoniazid and rifapentine versus 9-month course of isoniazid in latent tuberculosis infection
Secondary ID [1] 282479 0
Nil
Universal Trial Number (UTN)
U1111-1142-8697
Trial acronym
SIRCLE (Short-course Isoniazid and Rifapentine for Cost-effective Latent tuberculosis Eradication)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Latent tuberculosis infection 289106 0
Condition category
Condition code
Infection 289444 289444 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A 12 dose course of weekly isoniazid (900mg) and rifapentine (900mg) tablets.
Intervention code [1] 287126 0
Treatment: Drugs
Intervention code [2] 287242 0
Prevention
Comparator / control treatment
A 270 dose course of daily isoniazid tablets (300mg)
Control group
Active

Outcomes
Primary outcome [1] 289546 0
Cost-benefit of 12 dose isoniazid/rifapentine versus 270 dose isoniazid, in AUD per completed course of preventative therapy. Treatment completion is defined as administration of >90% doses of prescribed medication within 16 weeks for short-course isoniazid and rifapentine (3HR) or 12 months for standard course of isoniazid (9H). Medication doses will be assessed clinically and via pharmacy dispensation records. Costs will be assessed from the perspective of the healthcare system, in AUD.
Timepoint [1] 289546 0
End of treatment
Secondary outcome [1] 302707 0
Treatment completion rate (defined as administration of >90% doses of prescribed medication within 16 weeks for 3HR or 12 months for 9H). Medication doses will be assessed clinically and via pharmacy dispensation records.
Timepoint [1] 302707 0
End of treatment
Secondary outcome [2] 302708 0
Patient satisfaction between 9H and 3HR, self-reported using a questionnaire with Likert scales.
Timepoint [2] 302708 0
End of treatment
Secondary outcome [3] 302709 0
Staff satisfaction between 9H and 3HR, self-reported using a questionnaire with Likert scales.
Timepoint [3] 302709 0
End of trial

Eligibility
Key inclusion criteria
Males and non-pregnant, non-breastfeeding females

Weight > 45kg

Willingness to provide signed informed consent.

Sufficient English-language skills for informed consent.

Clinical indication for latent tuberculosis infection (LTBI) treatment. 1) Person with a positive interferon-gamma release assay (IGRA) (defined as >0.35 IU/mL TB antigen-Nil) AND one of the following: close contact to someone with culture confirmed TB or from a high-risk background, current or planned immunosuppressive therapy, or calcification on chest X-ray and no prior history of TB treatment; 2) IGRA converters defined as a documented change from negative to positive within a two-year period; 3) Persons with any other clinical indication for LTBI treatment including persons with a negative IGRA (eg high risk clinical history and pending immunosuppressive therapy)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Confirmed or suspected active TB disease

Contacts to a source case with known resistance to isoniazid and/or rifampicin

Persons with a history (by written documentation or self-report) of ever receiving > 1 week of treatment for active or latent TB.

History of allergy or intolerance to isoniazid or rifamycins

Serum alanine aminotransferase (ALT) > 100 IU/L

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)
Potential participants will be enrolled via the outpatient clinics of the Victorian Infectious Diseases Service. 80 participants meeting inclusion criteria will be enrolled and randomly allocated to intervention or control group in a non-blinded fashion. Allocation will be performed by a pharmacist not involved in eligibility assessment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be 1:1 and performed according to random sequence computer generated prior to trial enrollment.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Sample size for this study has been calculated to consider cost differences between the intervention and control groups. Assuming an expected difference of 200$ between cost of the regimens, 36 participants per group will have a power of 80% to detect a difference with a=0.05.
Cost-benefit analysis will be performed, comparing total costs associated with each of 9H vs 3HR in AUD. Costs will be assessed at the level of the healthcare system. Pre-determined costs for each outpatient visits and medication dispensed will be calculated in AUD. As Rifapentine is not currently PBS listed, expected costs will be taken from US commercial prices, in AUD, and sensitivity analysis will also be performed to consider the potential effect of price on overall costs. Any hospitalisation for side effects of therapy will be included, including additional pathology tests and a daily cost of hospitalisation. Daily costs associated with hospitalisation will be taken from National Hospital Cost Data Collection estimates. The relevant Medicare Benefit Schedule fee for any pathology or radiology tests will be applied to tests performed in an outpatient setting.
Descriptive statistical analyses will be presented with regards to treatment adherence, adverse effects and end-of-treatment patient and staff satisfaction. Secondary analyses will be compared to consider differences in event frequency with inter-group comparisons made with chi2 analysis or Fisher’s exact test for categorical variables and the Mann-Whitney test for continuous variables. P-values will be calculated and considered significant if p<0.05. All calculation of probabilities will employ two-tailed tests.

Recruitment
Recruitment status
Completed
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)
VIC
Recruitment hospital [1] 979 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 6874 0
3050 - Royal Melbourne Hospital

Funding & Sponsors
Funding source category [1] 287257 0
Charities/Societies/Foundations
Name [1] 287257 0
John Burge Estate
Address [1] 287257 0
State Trustees Limited
168 Exhibition Street
Melbourne, VIC 3000
Country [1] 287257 0
Australia
Primary sponsor type
Hospital
Name
Melbourne Health
Address
Royal Melbourne Hospital
Grattan Street
Parkville, VIC 3050
Country
Australia
Secondary sponsor category [1] 286011 0
None
Name [1] 286011 0
Address [1] 286011 0
Country [1] 286011 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289237 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 289237 0
Level 6, Main Building, Royal Melbourne Hospital, Grattan Street, Parkville VIC 3050
Ethics committee country [1] 289237 0
Australia
Date submitted for ethics approval [1] 289237 0
Approval date [1] 289237 0
07/05/2013
Ethics approval number [1] 289237 0
2013.036

Summary
Brief summary
The aim of this study is to perform a multimodal comparison of 3-month courses of weekly isoniazid and rifapentine (3HR) with 9 months of daily isoniazid (9H) for latent tuberculosis infection, using a variety of indices:

a. Cost-benefit
b. Patient satisfaction
c. Adherence to prescribed therapy
Trial website
Nil
Trial related presentations / publications
NA
Public notes

Contacts
Principal investigator
Name 39926 0
Dr Justin Denholm
Address 39926 0
Victorian Infectious Diseases Service
9N, Main Building, Royal Melbourne Hospital
Grattan Street, Parkville VIC 3050
Country 39926 0
Australia
Phone 39926 0
+61 3 9342 7000
Fax 39926 0
Email 39926 0
justin.denholm@mh.org.au
Contact person for public queries
Name 39927 0
Dr Justin Denholm
Address 39927 0
Victorian Infectious Diseases Service
9N, Main Building, Royal Melbourne Hospital
Grattan Street, Parkville VIC 3050
Country 39927 0
Australia
Phone 39927 0
+61 3 9342 7000
Fax 39927 0
Email 39927 0
justin.denholm@mh.org.au
Contact person for scientific queries
Name 39928 0
Dr Justin Denholm
Address 39928 0
Victorian Infectious Diseases Service
9N, Main Building, Royal Melbourne Hospital
Grattan Street, Parkville VIC 3050
Country 39928 0
Australia
Phone 39928 0
+61 3 9342 7000
Fax 39928 0
Email 39928 0
justin.denholm@mh.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary