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Trial registered on ANZCTR


Registration number
ACTRN12618000733279
Ethics application status
Approved
Date submitted
16/04/2018
Date registered
2/05/2018
Date last updated
3/06/2019
Date data sharing statement initially provided
3/06/2019
Date results information initially provided
3/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Pilot study to determine the effect on cardiac output of standard pulmonary rehabilitation exercises in patients with pulmonary hypertension
Scientific title
Pilot study to determine the effect on cardiac output of standard pulmonary rehabilitation exercises in patients with pulmonary hypertension
Secondary ID [1] 294539 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
pulmonary hypertension 307321 0
Condition category
Condition code
Respiratory 306429 306429 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a one arm trial.
The intervention involves a single session of exercise testing performed following medical review in a hospital clinic. Following a routine clinical appointment with an individual's treating respiratory physician, participants will return to the Respiratory Laboratory and, under the supervision of a senior exercise physiologist (minimum 7 years experience) and respiratory scientist, will perform a 6 minute walk test (which is part of standard care) and 3 additional exercises (which reflect the standard exercises prescribed during community-based stage 1 pulmonary rehabilitation) with pre- and post-exercise testing using a novel breathing test – Innocor.
[The Innocor measures a surrogate for cardiac output utilising an inert gas rebreathing technique, and a relatively simple breathing manoeuvre with inhalation of a gas containing a mixture of soluble (nitrous oxide; N20) and insoluble (sulphur hexafluoride; SF6) gas. CO is proportional to the rate of decline of the soluble compound (N20) as it is cleared by the pulmonary circulation. Innocor haemodynamic measurements have been validated against
gold standard right heart catheterisation (RHC) and cardiac MRI, and have been shown to detect response to treatment in pulmonary hypertension.]
The exercises selected are prescribed commonly within the local Community Pulmonary Rehabilitation program and are translatable to what would be performed in the outpatient setting. The exercises are:
1. Upper limb resistance exercises for 6 minutes (including rests between sets) involving ten repetitions of each of four upper limb exercises: the downward diagonal cross arm lift, single alternating arm military press (shoulder press), forward arm lift and double arm row.
2. Stationary exercise bike for 6 minutes, at 60 revolutions per minute, with documentation of work rate achieved (Watts)
3. Sit to stand and step up for 6 minutes (including rests between sets).
The absolute intensity of the exercise will be individualised for each participant, through the participant's self-reported rating of perceived exertion and the clinical judgement of the exercise physiologist. The relative intensity of the exercise will be standardised across all participants (moderate intensity exercise).
The overall session will be 30-45 minutes in duration (depending on the duration of rest required between exercise bouts) and will be completed under the direct supervision of the researchers.
Intervention code [1] 300836 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305523 0
Change in Innocor-measured cardiac output from pre-exercise to post-exercise for each of the four exercise bouts.
Timepoint [1] 305523 0
Innocor is tested before and after each of the four 6 minute exercise bouts ((1) 6minute walk test, (2) Upper limb resistance band exercises, (3) Stationary exercise bike and, (4) Lower limb resistance exercise). There is only a single data collection session for this study and all data is collected during this session.
Primary outcome [2] 305524 0
Change in Innocor-measure stroke volume (mL) from pre-exercise to post-exercise for each of the four exercise bouts.
Timepoint [2] 305524 0
Innocor is tested before and after each of the four 6 minute exercise bouts ((1) 6minute walk test, (2) Upper limb resistance band exercises, (3) Stationary exercise bike and, (4) Lower limb resistance exercise). There is only a single data collection session for this study and all data is collected during this session.
Primary outcome [3] 305525 0
Number of exercise-related adverse events, of a grade 3 or above, that occur during or following (within 30 minutes of) the four exercise bouts. Adverse events will be defined and graded using the Common Terminology Criteria for Adverse Events (CTC-AE), as assessed by supervising Exercise Physiologist. Examples of adverse events could include (but are not limited to): fall, sprain, fracture, injury, episode of low blood sugar, strain, pull, tear of muscle or bone, dizziness.
Timepoint [3] 305525 0
During or following (within 30 minutes of) the four 6-minute exercise bouts that are completed on during a single data collection session.
Secondary outcome [1] 345583 0
Physical activity level (minutes of physical activity in the past 7 days) based on participant recall questionnaire (Active Australia Survey)
Timepoint [1] 345583 0
Prior to exercise bouts during the single data collection session (i.e., on day of exercise testing).
Secondary outcome [2] 345584 0
Respiratory function (Forced Expiratory Volume 1 second, L/min), assessed via spirometry
Timepoint [2] 345584 0
Prior to exercise bouts during the single data collection session (i.e., on day of exercise testing).
Secondary outcome [3] 345585 0
Respiratory function (Forced Vital Capacity, L/min), assessed via spirometry
Timepoint [3] 345585 0
Prior to exercise bouts during the single data collection session (i.e., on day of exercise testing).
Secondary outcome [4] 345586 0
Respiratory function (Diffusion Capacity of the lungs for Carbon Monoxide mL/ mmHg/ min), assessed via spirometry
Timepoint [4] 345586 0
Prior to exercise bouts during the single data collection session (i.e., on day of exercise testing).
Secondary outcome [5] 345587 0
Physical function assessed via the Six Minute Walk Test (distance walked, metres)
Timepoint [5] 345587 0
Single data collection session (i.e., on day of exercise testing).
Secondary outcome [6] 345588 0
Safety (Percentage of patients with a drop in cardiac output [as measured by Innocor] of >10% between pre and post exercise bout)
Timepoint [6] 345588 0
Innocor is tested before and after each of the four 6 minute exercise bouts. There is only a single data collection session for this study and all data is collected during this session.

Eligibility
Key inclusion criteria
*18 years and older
*Diagnosis of pulmonary hypertension
*Stable disease as defined by no changes to pulmonary vasodilator therapy in the previous 3 months
*New York Heart Association / WHO functional class I, II or III symptoms
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Patients not able to give informed consent
*Musculoskeletal or neurological disorders that prevent exercise
*Patients with absolute contraindications to respiratory function testing


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



Intervention assignment
Single group
Other design features
Not applicable
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
This is a pilot study involving novel testing in this relatively rare and under-studied population. Given the exploratory nature of the study and the scarcity of relevant data, the sample size was based on the number of patients seen in the clinic over a 6-month period.
Demographic data will be presented as mean +/- standard deviation for continuous variables and as number (percentage or proportion) for categorical variables. The change (post exercise - pre exercise) in cardiac output and stroke volume will described as a mean +/- standard deviation for each of the exercises performed if the data is normally distributed. If there is a negative delta cardiac output (post exercise - pre exercise) the percentage of patients with a delta of >10% will be calculated for each exercise. The number of adverse events will be described.

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)
QLD
Recruitment hospital [1] 10682 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 22402 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 299165 0
Hospital
Name [1] 299165 0
Princess Alexandra Hospital
Address [1] 299165 0
Metro South Health's Study, Education and Research Trust Level 7, Translational Research Institute
37 Kent St
Woolloongabba QLD 4102
Country [1] 299165 0
Australia
Primary sponsor type
Hospital
Name
Department of Respiratory and Sleep Medicine, Princess Alexander Hospital
Address
Department of Respiratory and Sleep Medicine
Princess Alexandra Hospital
199 Ipswich Road,
Woolloongabba QLD 4102
Country
Australia
Secondary sponsor category [1] 298486 0
None
Name [1] 298486 0
Address [1] 298486 0
Country [1] 298486 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300089 0
Metro South Health, Human Research Ethics Committee
Ethics committee address [1] 300089 0
PAH Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [1] 300089 0
Australia
Date submitted for ethics approval [1] 300089 0
17/01/2018
Approval date [1] 300089 0
27/02/2018
Ethics approval number [1] 300089 0
HREC/18/QPAH/47

Summary
Brief summary
Pulmonary hypertension (PH), characterised by elevated pressure within the blood vessels of the lungs, is associated with progressive breathlessness, functional limitation and increased risk of death. PH has unacceptably low survival with 1, 3 and 5 year median survival rates only 85%, 66% and 53%. Exercise has recently been found to be beneficial in PH, with benefits similar to pharmacotherapy (Morris 2016). Traditionally patients with PH have not been included in exercise programs due to safety concerns. However, a recent Cochrane review of 6 RCTs including 206 patients, reported only a single adverse event (in which training was stopped for a single session due to lightheadedness).
This pilot study proposes to assess
1. the feasibility of Innocor testing in conjunction with exercise testing to assess the cardiac output of patients with stable PH.
2. the safety of four 6-minute bouts of exercise a in a cohort of stable PH patients.
This will be achieved through realtime measurement of cardiac response to standard Pulmonary Rehabilitation exercises in a cohort of patients with known stable PH. This pilot project is the first of its kind to assess using the Innocor, a breathing test from which cardiac output can be calculated.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82534 0
Dr Claire Ellender
Address 82534 0
Department of Respiratory and Sleep Medicine
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba QLD 4102
Country 82534 0
Australia
Phone 82534 0
+61 7 3176 2698
Fax 82534 0
+61 7 3176 6170
Email 82534 0
claire.ellender@health.qld.gov.au
Contact person for public queries
Name 82535 0
Dr Claire Ellender
Address 82535 0
Department of Respiratory and Sleep Medicine
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba QLD 4102
Country 82535 0
Australia
Phone 82535 0
+61 7 3176 2698
Fax 82535 0
+61 7 3176 6170
Email 82535 0
claire.ellender@health.qld.gov.au
Contact person for scientific queries
Name 82536 0
Dr Claire Ellender
Address 82536 0
Department of Respiratory and Sleep Medicine
Princess Alexandra Hospital
199 Ipswich Road, Woolloongabba QLD 4102
Country 82536 0
Australia
Phone 82536 0
+61 7 3176 2698
Fax 82536 0
+61 7 3176 6170
Email 82536 0
claire.ellender@health.qld.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
No protocol is in place for data sharing at this point but CIs are open to discussions regarding IPD sharing.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary