Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001737123p
Ethics application status
Submitted, not yet approved
Date submitted
15/11/2019
Date registered
9/12/2019
Date last updated
9/12/2019
Date data sharing statement initially provided
9/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
High-intensity interval training within cardiac rehabilitation: a multi-center randomized controlled trial.
Scientific title
Comparison of high-intensity interval training and moderate-intensity continuous training in patients with coronary artery disease on completion rates within cardiac rehabilitation service.
Secondary ID [1] 299763 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary artery disease 315125 0
Condition category
Condition code
Cardiovascular 313471 313471 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
High-intensity interval training (HIIT)
HIIT consists of 6 weeks x 2 sessions/week (12 sessions), involving stationary cycling of 15-20 repetitions × 30-second intervals at 85-90% HRmax (RPE ~14-17), interspersed with 30-second active recovery. Each session will begin with a 10-minute moderate-intensity warm-up at ~65% HRmax and ended with a 5-minute active recovery cool-down. For the first 3-weeks of training, all patients will complete 15 repetitions per session (including 2 passive rests for BP measurement – after the 5th and 10th repetition); in the final 3-weeks of training, patients will complete 20 repetitions per session (including 1 passive rest – after the 10th repetition). The passive rest periods will be ~30-seconds or until BP measurement has been accurately recorded. Workloads are determined by the clinical staff (physiotherapists and exercise physiologists) to maintain the target HR (and/or RPE) range for the 5- or 10-repetition block (before a passive rest for BP measurement). HR and RPE will be recorded in the last 5 seconds of every 5th work interval. HR and BP will be monitored during the cool-down period to ensure patient safety. The total time commitment for each HIIT session is 30 minutes (for 15 total repetitions) to 35 minutes (for 20 total repetitions), equating to mean across all sessions 32.5 minutes.
Intervention code [1] 316041 0
Treatment: Other
Comparator / control treatment
Moderate-intensity continuous training (MICT), which is typically considered as 'usual care' which CR services.
The MICT programme consists of 6 weeks x 2 sessions/week (12 sessions), involving stationary cycling of 35-43 minutes continuous cycling at 65-70% HRmax (RPE ~11-13). Workloads will be adjusted the clinical staff based on HR response over the duration of the training session to maintain the HR range, as such, workloads will likely change within individual training sessions. HR, RPE and workload will be recorded every 5 minutes. No warm-up or cool-down is required due to the moderate-intensity of the training. Training progression will be provided via increased time duration - for the first 3 weeks, MICT will be 35 min; for the last 3 weeks of training, MICT will be 43min. The total time commitment for each MICT session is 35 to 43 minutes, equating to mean across all sessions 39 minutes.
Control group
Active

Outcomes
Primary outcome [1] 321974 0
Completion rate, defined as a minimum of 10 completed training sessions.
Timepoint [1] 321974 0
Post-training
Secondary outcome [1] 376881 0
Blood Pressure
Blood pressure (resting) will be assessed using an automated, upper-arm cuff-oscillometric sphygmomanometer (Omron HEM-907, Kyoto, Japan). This will provide measures of brachial systolic pressure, diastolic pressure, mean arterial pressure and resting heart rate. The measure will be conducted after 5 minutes seated rest.
Timepoint [1] 376881 0
Pre-training (2-5 days prior to first training session) vs post-training (within 2-5 days post-final training session)
Secondary outcome [2] 376882 0
Aerobic fitness
Aerobic fitness will be assessed by the 6-minute walk test (6MWT) and rate of heart rate recovery (HRR) following the 6MWT. 6MWT will be conducted using standard procedures. Patients are instructed to walk as far as possible along a 30-meter corridor for 6 minutes, to achieve their maximum possible walking distance. Standardized instructions are provided during tests, and HR and RPE will be measured. HRR will be assessed by the change in HR at 1-minute post-test (seated rest immediately upon test termination) compared to HR reached during the test (recorded in last 5 seconds of the test).
Timepoint [2] 376882 0
Pre-training (2-5 days prior to first training session) vs post-training (within 2-5 days post-final training session)
Secondary outcome [3] 376883 0
Safety
Exercise-related adverse events (AE), defined as occurring during or up to 4 hours following a HIIT or MICT session, will be recorded. All other AEs are also recorded. All exercise-related AEs will be reviewed by the data safety monitoring board comprised of three clinicians, including two cardiologists. AEs will be categorised according to origin (cardiovascular or non-cardiovascular) and severity (minor – stable, symptoms relieved without requiring intervention by the CR CNC; or major – unstable and requiring immediate emergency intervention, or persistent signs or symptoms requiring CR CNC review).
Timepoint [3] 376883 0
Post-training
Secondary outcome [4] 376884 0
Affective state (composite outcome)
The Depression Anxiety Stress scale (DASS21), the Positive and Negative Affect Schedule (PANAS) and the MacNew Heart Disease Health-related Quality of Life questionnaire (MacNew) will be applied. DASS is a 21-item questionnaire using a 4-point Likert scale (0 = not at all; 3 = very often or very much) to analyse negative emotional states in the previous week. PANAS is a 20-item questionnaire using a 5-point Likert scale (1 = not at all or only slightly; 5 = extremely) to analyse both positive and negative feelings and emotions in the previous week. The MacNew questionnaire consists of 27 items covering physical limitations, emotional function and social function.
Timepoint [4] 376884 0
Pre-training (2-5 days prior to first training session) vs post-training (within 2-5 days post-final training session)
Secondary outcome [5] 376885 0
Hospital re-admissions at 3mth follow-up
At 3 months following participation in the training intervention, patients will be contacted via phone. Incidence of hospital re-admission will be recorded.
Timepoint [5] 376885 0
3 months post-training
Secondary outcome [6] 376886 0
Physical activity habits at 3-month follow-up.
At 3 months following participation in the training intervention, patients will be contacted via phone. Physical activity patterns during the 3 months following study involvement will be discussed using a semi-formal interview style, and incidence of sedentary behaviours (no formal exercise training post-study) or maintenance of regular HIIT or MICT will be recorded.
Timepoint [6] 376886 0
3 months post-training
Secondary outcome [7] 377752 0
Total percent body fat
Assessed using bioelectrical impedance analysis (BIA) scales
Timepoint [7] 377752 0
Pre-training (2-5 days prior to first training session) vs post-training (within 2-5 days post-final training session)
Secondary outcome [8] 377753 0
Body mass index (BMI)
Calculated from height measured using a stadiometer and weight measured using calibrated scales
Timepoint [8] 377753 0
Pre-training (2-5 days prior to first training session) vs post-training (within 2-5 days post-final training session)
Secondary outcome [9] 377754 0
Waist circumference
Measured via tape measure in the horizontal at the point of the umbilicus
Timepoint [9] 377754 0
Pre-training (2-5 days prior to first training session) vs post-training (within 2-5 days post-final training session)

Eligibility
Key inclusion criteria
1. Age between 18 and 75 years
2. Documented coronary artery disease (CAD), specifically recent acute myocardial infarction (MI), percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG), or, treated valvular heart disease, specifically following valve repair or replacement
3. Clinically stable for at least 4 weeks following AMI or PCI, or 6 weeks following CABG or other surgery requiring sternotomy
4. NYHA Class I
5. Sinus rhythm
6. First-time participant at the CR
7. Left ventricular ejection fraction > 40%
8. Receiving optimal medical treatment
9. Successful completion of a 2 session ‘run-in’ period of exercise training at the CR (‘usual care’ consisting of low to moderate-intensity continuous aerobic exercise and light-intensity resistance exercises).
10. Treating cardiologist’s clear approval for participation
11. Negative exercise stress test result
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Primary diagnosis of heart failure; having a pacemaker; haemodynamically significant valvular disease; severe chronic obstructive pulmonary disease; unstable symptomatology; post-surgical tachycardia; cognitive impairment; not fluent in English; unable to undertake cycling exercise; women lactating, pregnant or of childbearing potential who are not willing to avoid becoming pregnant during the study; or other co-morbidities precluding participation in a structured exercise programme.

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 the holder of the allocation schedule (the lead investigator) who is "off-site" contacting the head physiotherapists at each CR site prior to the participant's first training session but after enrolment and all baseline assessments. The CNC conducting the enrolment process and baseline assessments will be blinded to allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A random number sequence generated by an independent statistician will be used to determine the 3:1 block randomised allocation sequence. Participants will be informed of their randomised group allocation upon arrival to the first training session, after enrolment into the study and after completion of all pre-training assessments.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Parallel
Other design features
Participants cannot be blinded to their training group allocation but will be blinded to the hypotheses of the study and to their baseline assessment data. Researchers conducting or supervising the training sessions cannot be blinded to the training group allocation. Researchers performing all outcome assessments will be unblinded to the participant’s training group allocation. Researchers conducting the data analysis will be blinded.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The sample size calculation is based on a significant difference between the two groups for the completion rates. Therefore, with power of 0.8 and a 0.05 significance level, and anticipating a 5% drop-out rate (loss to follow-up) for the HIIT intervention (based on feasibility study findings of 95.8% completion) and 35% drop-out rate for the MICT intervention (based on historical CR site completion rates for usual care for the analogous study population in terms of age and CAD indication for CR referral) in addition to accounting for the 3:1 allocation, we calculate a minimum of 64 participants will be required (HIIT N = 48, MICT N = 16).

Analyses will be performed using standard statistical software (IBM Statistical Package for Social Sciences; SPSS version 25, Chicago, IL, USA). Shapiro-Wilk tests will be applied to assess normality of the continuous variables. Unadjusted tests of group differences at follow-up will be examined using independent samples t-test for continuous, normally-distributed variables. Assuming no missing data, paired-samples t-tests will be applied for within group comparisons (pre vs post). If there are missing data, mixed models will be used to obtain test change over time. Mixed models will also be used to obtain adjusted tests between and within groups differences. If data violate normality assumptions, then appropriate transformations or non-parametric tests will be used. Pearson’s Chi-square test will be applied to assess associations among categorical variables. Effect sizes will be calculated using Cohen’s d for normally-distributed outcomes or Cliff’s D for non-normally distributed outcomes. Variables will be presented as mean ± standard deviation or median (inter-quartile range) (for continuous variables) or frequencies (percentages) (for categorical variables). Significance is set at p < 0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/02/2020
Actual
Date of last participant enrolment
Anticipated
3/10/2022
Actual
Date of last data collection
Anticipated
4/01/2023
Actual
Sample size
Target
64
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 15168 0
Prince of Wales Hospital - Randwick
Recruitment hospital [2] 15169 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 28470 0
2031 - Randwick
Recruitment postcode(s) [2] 28471 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 304230 0
Charities/Societies/Foundations
Name [1] 304230 0
Prince of Wales Hospital Foundation
Country [1] 304230 0
Australia
Primary sponsor type
Hospital
Name
Prince of Wales Hospital
Address
320-346 Barker St, Randwick NSW 2031
Country
Australia
Secondary sponsor category [1] 304469 0
Hospital
Name [1] 304469 0
Royal Prince Alfred Hospital
Address [1] 304469 0
50 Missenden Rd, Camperdown NSW 2050
Country [1] 304469 0
Australia
Secondary sponsor category [2] 304535 0
University
Name [2] 304535 0
University of New South Wales
Address [2] 304535 0
UNSW Sydney
High St
Kensington, NSW 2052
Australia
Country [2] 304535 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 304691 0
South Eastern Sydney Local Health District HREC
Ethics committee address [1] 304691 0
District Executive Unit, Level 4
The Sutherland Hospital & Community Health Service
Cnr The Kingsway & Kareena Road
Caringbah, NSW 2229
Ethics committee country [1] 304691 0
Australia
Date submitted for ethics approval [1] 304691 0
14/11/2019
Approval date [1] 304691 0
Ethics approval number [1] 304691 0
2019/ETH10609

Summary
Brief summary
This trial will compare high-intensity exercise delivered in short bursts (intervals) against the typical moderate intensity exercise that is used during cardiac rehabilitation. The study will be a randomised controlled trial. Endpoints that will be examined include aerobic fitness, blood pressure and body fat percentage.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97882 0
Dr Andrew Keech
Address 97882 0
University of New South Wales
School of Medical Sciences
Wallace Wurth building
Randwick, Sydney NSW 2052
Country 97882 0
Australia
Phone 97882 0
+61 2 9385 8331
Fax 97882 0
Email 97882 0
[email protected]
Contact person for public queries
Name 97883 0
Dr Andrew Keech
Address 97883 0
University of New South Wales
School of Medical Sciences
Wallace Wurth building
Randwick, Sydney NSW 2052
Country 97883 0
Australia
Phone 97883 0
+61 2 9385 8331
Fax 97883 0
Email 97883 0
[email protected]
Contact person for scientific queries
Name 97884 0
Dr Andrew Keech
Address 97884 0
University of New South Wales
School of Medical Sciences
Wallace Wurth building
Randwick, Sydney NSW 2052
Country 97884 0
Australia
Phone 97884 0
+61 2 9385 8331
Fax 97884 0
Email 97884 0
[email protected]

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 of the individual participant data collected during the trial, after de-identification
When will data be available (start and end dates)?
Immediately following publication, no end date
Available to whom?
anyone who wishes to access it
Available for what types of analyses?
any purpose
How or where can data be obtained?
Contacting the lead investigator (email: [email protected])


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
5716Study protocol    378706-(Uploaded-15-11-2019-13-42-31)-Study-related document.docx



Results publications and other study-related documents

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