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Trial registered on ANZCTR


Registration number
ACTRN12616001596493
Ethics application status
Approved
Date submitted
16/11/2016
Date registered
18/11/2016
Date last updated
6/11/2019
Date data sharing statement initially provided
6/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of different intensity exercise training in patients with ventricular assist devices
Scientific title
The effects of different intensity exercise training on peak oxygen consumption in patients with left ventricular assist devices: a multicentre, randomized, control trial.
Secondary ID [1] 287931 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Exercise Training in Ventricular Assist Devices (ETVAD)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Chronic Heart Failure with Left Ventricular Assist Device in situ. 296808 0
Condition category
Condition code
Cardiovascular 300288 300288 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
High-intensity Interval Training (HIT):
This is an intervention of 12-week exercise training program involving high-intensity interval training three times per week. The total duration of each session will be 60 minutes.
- The intervention will be delivered by an Exercise Physiologist with minimum 3 years' experience and will be supervised by a multidisciplinary team composed of Senior Exercise Physiologists, Senior Physiotherapists and a Registered Nurse in a hospital-based cardiac rehabilitation gymnasium.
- Sessions in both groups will commence/conclude with a warm-up/cool-down involving 5 minutes of low-intensity aerobic exercise, followed by 5 minutes of stretching.
-Following warm up, 4 sets of 4-minute of aerobic exercise on a treadmill at 80-90% of VO2 reserve, interspersed with 3-minute intervals of active recovery at 50-60% of VO2 reserve.
-Resistance exercises, involving one set of 3 lower body (dual leg press, dual seated hamstring curl, dual leg extension) and 3 upper body exercises (incline press, lat pull down and biceps curl) at 50-75% of one-repetition maximum..
-The exercise training program will be reviewed every fortnight during the course of the intervention to adapt the exercise prescription for cardiopulmonary and strength changes.
- Adherence to exercise training program will be monitored at the cardiac rehabilitation gym on a daily basis, with exercise attendance log and mobile call for follow up in case of non-attendance. Compliance will be set as 90% adherence to the established exercise training program.
Intervention code [1] 293281 0
Rehabilitation
Comparator / control treatment
Moderate-intensity Continuous Training (usual care):
-12-week exercise training program involving moderate-intensity continuous exercise training (MIT) three times per week. The total duration of each session will be 60 minutes.
-The intervention will be delivered by an Exercise Physiologist with minimum 3 years' experience and will be supervised by a multidisciplinary team composed of Senior Exercise Physiologists, Senior Physiotherapists and a Registered Nurse in a hospital-based cardiac rehabilitation gymnasium.
- Identical warm up and cool down as HIT group.
-Following warm up, 28 minutes of continuous treadmill exercise at 50-60% of VO2 reserve.
- Identical resistance training program as HIT group.
- The exercise training program will be also reviewed every fortnight in this group during the course of the intervention to adapt the exercise prescription for cardiopulmonary and strength changes.
- Adherence to exercise training program will be monitored at the cardiac rehabilitation gym on a daily basis, with exercise attendance log and mobile call for follow up in case of non-attendance. Compliance will be set as 90% adherence to established exercise training program.
Control group
Active

Outcomes
Primary outcome [1] 296639 0
Peak oxygen consumption (VO2 peak), measured by cardiopulmonary exercise test.
Timepoint [1] 296639 0
After 12 weeks following intervention commencement.
Secondary outcome [1] 318964 0
Cardiac function and structure: An experienced echocardiographer will perform novel echocardiography assessment using post-hoc myocardial tissue imaging (speckle and strain) to assess changes in regional diastolic and systolic function.Left ventricular (LV) reserve will be determined using traditional LV dimensions (linear and volume). In addition, longitudinal strain will be assessed to evaluate the impact of exercise on residual contractility. Right heart function echo assessment will be measured in response to treadmill exercise to ascertain right heart response and how these relate to functional parameters.
-This is a composite outcome.
Timepoint [1] 318964 0
After 12 weeks following intervention commencement.
Secondary outcome [2] 328285 0
Endothelial function: Brachial artery blood flow will be evaluated using non-invasive high resolution duplex ultrasound to assess flow-mediated dilatation (FMD). Recorded images will be analysed employing edge-detection software.
Timepoint [2] 328285 0
After 12 weeks following intervention commencement.
Secondary outcome [3] 328286 0
Muscular Strength: Maximal isotonic voluntary strength measures will be assessed using a one-repetition maximum protocol to guide the prescription of the resistance exercise component of the training regimen. Body strength will be assess during a preliminary exercise training session when the participant will be orientated to all exercise training equipment.
Timepoint [3] 328286 0
After 12 weeks following intervention commencement.
Secondary outcome [4] 328287 0
Functional exercise capacity: This will be assessed using a six-minute walk test (6MWT) protocol.. Participants will perform two tests, at least 30 minutes apart with the best test recorded.
Timepoint [4] 328287 0
After 12 weeks following intervention commencement.
Secondary outcome [5] 328288 0
Overall body composition: Total body lean tissue mass, fat mass, bone mineral density, and visceral adipose tissue will be measured by dual-energy x-ray absorptiometry scan.
Timepoint [5] 328288 0
After 12 weeks following intervention commencement.
Secondary outcome [6] 328289 0
Blood samples will be collected to measure full blood count, creatinine, C-reactive protein, cholesterol, low-density lipoprotein, high-density lipoprotein (HDL), triglycerides, as well B-type natriuretic peptide (BNP) and N-terminal-pro-BNP (NT-pro-BNP).

- This is a composite secondary assessment.
Timepoint [6] 328289 0
After 12 weeks following intervention commencement.
Secondary outcome [7] 328290 0
Quality of Life (QoL): The Short Form 12 survey will be used to measure physical function, emotional state, social function, general health, mental health, and pain.

- This is a single secondary outcome, measured by a 12-question survey.
Timepoint [7] 328290 0
After 12 weeks following intervention commencement.
Secondary outcome [8] 328291 0
Heart disease Self-efficacy Scale: This validated questionnaire assesses an individuals perceived ability to undertake different tasks of a physical nature.
Timepoint [8] 328291 0
After 12 weeks following intervention commencement.
Secondary outcome [9] 353624 0
Cerebral blood flow (CBF): This is a composite secondary outcome which assesses cerebral perfusion response to exercise. Non-invasive insonation via 2MHz transcranial Doppler ultrasound (TCD; Spencer Technologies, Seattle, WA) is being used to assess blood velocity in the middle and posterior cerebral arteries (MCAv and PCAv, respectively). The MCAv and PCAv are continuously recorded at baseline, and throughout the exercise test.
Timepoint [9] 353624 0
After 12 weeks following intervention commencement.

Eligibility
Key inclusion criteria
- New York Heart Association (NYHA) Class III-IV chronic heart failure with left ventricular systolic dysfunction.
- At least 6 weeks post implantation with a continuous-flow LVAD (Heartware, HeartMate II/III)
- Haemodynamic stability.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any major co-morbidities that preclude exercise testing or training.
- Ventricular assist device complications including clotting, serious drive-line or systemic infections or mechanical problems.

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)
Automated clinical trials allocation system operated by a third party.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
1:1 ratio of participants.
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The sample size will be based on the power to identify a difference in the change in the primary outcome (peak VO2) of 2.5ml/kg/min, a clinically meaningful but conservative difference based on a previous study comparing HIT vs. MIT in CHF. Assuming a SD of 2.1 mL/Kg/min,at 80% power, 5% significance level, the samples size will be 14 per group . We will aim to recruit a total of 40 participants across the three sites to allow a 25% drop out or loss to follow up.

Linear regression models comparing group, adjusting for baseline, will be used to estimate group differences and 95%CI for change in the primary and secondary outcomes, using post-LVAD measures as the outcome, and conditioning by baseline measures, with treatment condition as a fixed factor. The intention-to-treat principle will be used for data analysis.

Recruitment
Recruitment status
Recruiting
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,WA,VIC
Recruitment hospital [1] 4685 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [2] 4687 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [3] 6789 0
The Alfred - Prahran

Funding & Sponsors
Funding source category [1] 292422 0
Charities/Societies/Foundations
Name [1] 292422 0
Heart Foundation -Vanguard Grant 2015
Address [1] 292422 0
In WA:
334 Rokeby Road Subiaco
Perth WA 6008

Mailing Address:
Heart Foundation WA Division
PO Box 1133, Subiaco WA 6904
Country [1] 292422 0
Australia
Funding source category [2] 294704 0
University
Name [2] 294704 0
Curtin University
Address [2] 294704 0
Kent Street, Bentley, Perth, WA 6102
Country [2] 294704 0
Australia
Primary sponsor type
University
Name
Curtin University
Address
Kent St, Bentley WA 6102
Country
Australia
Secondary sponsor category [1] 293548 0
None
Name [1] 293548 0
Address [1] 293548 0
Country [1] 293548 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293928 0
Royal Perth Hospital Human Research Ethics Committee (EC00270)
Ethics committee address [1] 293928 0
Southern Integrated Research Organisation (SIRO)

Level 2, Southern Research Facility (Perkins South Building)
102 – 118 Murdoch Drive
Murdoch WA 6150
Locked Bag 100 Palmyra DC WA 6961
Ethics committee country [1] 293928 0
Australia
Date submitted for ethics approval [1] 293928 0
13/11/2015
Approval date [1] 293928 0
Ethics approval number [1] 293928 0
REG 15-164
Ethics committee name [2] 296124 0
The Alfred HREC
Ethics committee address [2] 296124 0
OFFICE OF ETHICS & RESEARCH GOVERNANCE - Ground Floor, Linay Pavilion, The Alfred

The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria 3004, Australia
Ethics committee country [2] 296124 0
Australia
Date submitted for ethics approval [2] 296124 0
25/07/2016
Approval date [2] 296124 0
25/10/2016
Ethics approval number [2] 296124 0
HREC/16/Alfred/119

Summary
Brief summary
Many heart conditions impair the heart's ability to pump blood. This is known as heart failure. Exercise training is an important component in the management of heart failure, but in severe cases, symptoms such as breathlessness and fatigue limit patients' ability to undertake and benefit from exercise. Left ventricular assist devices (LVADs) are small pumps implanted into the heart of patients with severe heart failure to assist the heart in pumping blood around the body. LVADs reduce symptoms of heart failure, enabling patients to undertake exercise that wasn't previously possible. However, little is known about the most effective form of exercise training in patients with LVADs.

This research project will involve an international multicentre randomised controlled trial investigating the effects of a new approach of exercise training in patients with LVADs, involving alternating bouts of moderate and high-intensity exercise. Six weeks after being implanted with a LVAD, participants will be randomised to either 12 weeks of high-intensity interval exercise or 12 weeks of moderate intensity exercise. Before and after the exercise programs, participants will undergo tests to compare the effects of the two exercise programs on fitness, heart and blood vessel function and quality of life. We anticipate the findings of this project will help optimise exercise rehabilitation for people with LVADs and provide information that will help inform exercise prescription in people with cardiovascular disease more generally.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 61626 0
A/Prof Andrew Maiorana
Address 61626 0
Fiona Stanely Hospital -Advanced Heart Failure and Transplant Service
Locked Bag 100
Palmyra DC
6961 WA
Country 61626 0
Australia
Phone 61626 0
+61 4 33567369
Fax 61626 0
Email 61626 0
Andrew.Maiorana@health.wa.gov.au
Contact person for public queries
Name 61627 0
Mr Nacho Moreno Suarez
Address 61627 0
Curtin University - Building 101,
Health Sciences Research Hub

Kent Street, Bentley, Perth
WA 6102
Country 61627 0
Australia
Phone 61627 0
+61 4 03243221
Fax 61627 0
Email 61627 0
j.morenosuarez@postgrad.curtin.edu.au
Contact person for scientific queries
Name 61628 0
A/Prof Andrew Maiorana
Address 61628 0
Fiona Stanely Hospital -Advanced Heart Failure and Transplant Service
Locked Bag 100
Palmyra DC
6961 WA
Country 61628 0
Australia
Phone 61628 0
+61 4 33567369
Fax 61628 0
Email 61628 0
Andrew.Maiorana@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We do not have permission from all parties involved to release it.
What supporting documents are/will be available?
No other documents available
Summary results
No Results