Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000196842
Ethics application status
Approved
Date submitted
28/11/2020
Date registered
24/02/2021
Date last updated
24/02/2022
Date data sharing statement initially provided
24/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of Ivabradine use on exercise capacity in patients with transposition of the great arteries (TGA) post atrial switch repair
Scientific title
Effect of Ivabradine use on exercise capacity in patients with transposition of the great arteries (TGA) post atrial switch repair
Secondary ID [1] 303080 0
Nil
Universal Trial Number (UTN)
Trial acronym
IVAMUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Transposition of great arteries 319785 0
Congenital heart disease 319787 0
Condition category
Condition code
Cardiovascular 317716 317716 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Ivabradine
Dose: 5mg twice a day for first two weeks, then 5mg twice a day or 7.5mg twice a day for second two weeks according to heart rate check at two weeks.
Duration: 4 weeks
Mode of administration: oral tablet, overencapsulated
Adherence: RMH pharmacy will perform a pill count at two week and four week visits
Crossover occurs at 4 weeks with no washout required.
Intervention code [1] 319099 0
Treatment: Drugs
Comparator / control treatment
Placebo tablet consists of an inert filler (maize starch and pregelatinised maize starch), overencapsulated to preserve blinding.
Control group
Placebo

Outcomes
Primary outcome [1] 325761 0
Exercise capacity using a cardiopulmonary stress test (VO2 max), which will be performed on a stationary upright bicycle.
Timepoint [1] 325761 0
4 and 8 weeks; 4 weeks post commencement of intervention (ivabradine or placebo). Repeat test at 8 weeks (4 weeks after crossover)
Secondary outcome [1] 389049 0
Exercise duration in minutes (cardiopulmonary stress test)
Timepoint [1] 389049 0
4 and 8 weeks; 4 weeks post commencement of intervention (ivabradine or placebo). Repeat test at 8 weeks (4 weeks after crossover)
Secondary outcome [2] 389050 0
Exercise workload in watts (assessed on cardiopulmonary stress test)
Timepoint [2] 389050 0
4 and 8 weeks; 4 weeks post commencement of intervention (ivabradine or placebo). Repeat test at 8 weeks (4 weeks after crossover)
Secondary outcome [3] 390091 0
Heart rate response (% of maximum heart rate achieved for age on cardiopulmonary stress test)
Timepoint [3] 390091 0
4 and 8 weeks; 4 weeks post commencement of intervention (ivabradine or placebo). Repeat test at 8 weeks (4 weeks after crossover)
Secondary outcome [4] 390092 0
Ventilatory efficiency (VE/VCO2 slope as assessed on cardiopulmonary stress test)
Timepoint [4] 390092 0
4 and 8 weeks;4 weeks post commencement of intervention (ivabradine or placebo). Repeat test at 8 weeks (4 weeks after crossover)
Secondary outcome [5] 390093 0
Quality of life (as assessed on SF-12 assessment tool)
Timepoint [5] 390093 0
4 and 8 weeks; 4 weeks post commencement of intervention (ivabradine or placebo). Repeat test at 8 weeks (4 weeks after crossover)

Eligibility
Key inclusion criteria
Age > 18
Transposition of great arteries with previous atrial switch repair
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Congestive heart failure
2. Unable to exercise
3. Not in sinus rhythm (atrial flutter/fibrillation)
4. Bradycardia or resting heart rate below 60bpm
5. Severe hepatic impairment
6. Combination with strong cytochrome P450 inhibitors (eg. Ketoconazole, macrolide antibiotics, HIV protease inhibitors, nefazodone) or with QT prolonging medications
7. Pregnancy, lactation
8. Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption (lactose excipient in tablet)

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)
Allocation involves pharmacy team contacting statistician who is holder of allocation schedule and offsite
Researchers blinded to treatment allocation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using randomisation schedule generated by a computer
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data will be prospectively recorded. We will analyse baseline variables to assess whether these exist any baseline differences between those allocated to placebo or Ivabradine at randomisation. The primary endpoint is change in VO2max; mean change in VO2 max will be compared as a continuous variable (between baseline and 2 weeks, then between 2 and 4 weeks) and the change in VO2 max will be also analysed as a categorical variable (no change, improvement, deterioration). We will also assess changes in secondary end-points as follows: exercise duration (minutes) and workload (METS), heart rate response (% maximum predicted heart achieved and chronotropic reserve) and ventilatory efficiency (VE/VCO2). Changes in quality of life will also be assessed.

Analysis will be performed on a per protocol basis. Continuous variables will be presented as mean ± standard deviation and baseline differences between groups will be compared using the independent sample t-test. Categorical variables will be presented as proportions and compared by Chi-squared analysis. A mixed effect regression model will be used to investigate the overall impact of treatment (Ivabradine) on the change in VO2max and other measures. Data will be exported from the database as a CSV file for analysis. All data will be analysed using the Statistical program of social sciences (SPSS, version 24)

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/03/2021
Actual
3/05/2021
Date of last participant enrolment
Anticipated
31/12/2022
Actual
Date of last data collection
Anticipated
2/01/2023
Actual
Sample size
Target
20
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 18057 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 18117 0
Royal Melbourne Hospital - Royal Park campus - Parkville
Recruitment postcode(s) [1] 32035 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 303940 0
Hospital
Name [1] 303940 0
Royal Melbourne Hospital
Country [1] 303940 0
Australia
Primary sponsor type
Hospital
Name
Melbourne Health
Address
Royal Melbourne Hospital
Royal Parade
Parkville
Victoria
3052
Country
Australia
Secondary sponsor category [1] 304091 0
None
Name [1] 304091 0
Address [1] 304091 0
Country [1] 304091 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304436 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 304436 0
Office for research, Level 2 south west, Royal Melbourne Hospital, Royal Parade, Parkville, Victoria 3052
Ethics committee country [1] 304436 0
Australia
Date submitted for ethics approval [1] 304436 0
26/02/2019
Approval date [1] 304436 0
24/06/2019
Ethics approval number [1] 304436 0
2020.017

Summary
Brief summary
This is a single centre, randomized, double blind, cross over study designed to assess the effect of Ivabradine (as a heart rate lowering drug) on the exercise capacity of adults with transposition of the great arteries who have had a previous atrial switch repair. Subjects will be randomised to Ivabradine or placebo after undergoing a baseline cardiopulmonary stress test. Repeat testing will be performed after 4 weeks of treatment then at 8 weeks after a crossover at 4 weeks. We hypothesise that heart rate lowering on exercise with improve exercise capacity (VO2 max) in these adults owing to improved blood flow through the heart (ie. improved atrio-ventricular transport).

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96950 0
Dr William Wilson
Address 96950 0
Department of Cardiology
Royal Melbourne Hospital
Parkville
Victoria
3052
Country 96950 0
Australia
Phone 96950 0
+61 488711976
Fax 96950 0
Email 96950 0
william.wilson@mh.org.au
Contact person for public queries
Name 96951 0
Dr William Wilson
Address 96951 0
Department of Cardiology
Royal Melbourne Hospital
Parkville
Victoria
3052
Country 96951 0
Australia
Phone 96951 0
+61 488711976
Fax 96951 0
Email 96951 0
william.wilson@mh.org.au
Contact person for scientific queries
Name 96952 0
Dr William Wilson
Address 96952 0
Department of Cardiology
Royal Melbourne Hospital
Parkville
Victoria
3052
Country 96952 0
Australia
Phone 96952 0
+61 488711976
Fax 96952 0
Email 96952 0
william.wilson@mh.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All de-identified data will be available
When will data be available (start and end dates)?
Immediately following publication, no end date
Available to whom?
Anyone who wishes to see it
Available for what types of analyses?
Any purpose
How or where can data be obtained?
Access subject to approval by Principal investigator (email: william.wilson@mh.org.au)


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
9888Ethical approval    378473-(Uploaded-28-11-2020-18-35-22)-Study-related document.pdf
9889Informed consent form    378473-(Uploaded-28-11-2020-18-35-53)-Study-related document.docx


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.