Supervised Pulmonary Hypertension Exercise REhabilitation (SPHERe) trial

ISRCTN	ISRCTN10608766
DOI	https://doi.org/10.1186/ISRCTN10608766
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Integrated Research Application System (IRAS)	261218
Protocol serial number	HTA 17/129/02
Sponsor	University Hospitals Coventry & Warwickshire NHS Trust
Funder	Health Technology Assessment Programme

Submission date: 13/03/2019
Registration date: 18/03/2019
Last edited: 22/07/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Pulmonary hypertension is a disabling long-term condition that can greatly reduce quality of life. Blood vessels supplying the lungs become thick and stiff, restricting blood flow. Blood pressure is increased in these vessels meaning the heart must work harder to pump blood to the lungs. Over time, the heart may begin to fail. Breathlessness, fatigue and dizziness are the most common symptoms. People with pulmonary hypertension are often anxious about carrying out normal daily activities. There are five types of pulmonary hypertension with different causes. Medical treatment is different for each type, and may help to improve symptoms. Little is known about whether exercise rehabilitation may help people living with pulmonary hypertension. Supervised exercise rehabilitation is a common treatment for many heart and lung conditions. It can improve fitness, breathlessness, anxiety, depression, and quality of life. Some research has shown that exercise rehabilitation may be helpful for people with certain types of pulmonary hypertension: pulmonary arterial hypertension, and pulmonary hypertension due to blood clots in the lungs. Most of these exercise programmes included three weeks of intensive exercise as a hospital in-patient. This is not feasible in the NHS, where exercise rehabilitation is an outpatient service, typically lasting an hour, twice a week for eight weeks. It is not known whether outpatient/home-based exercise rehabilitation can help improve the lives of people with pulmonary hypertension. The aim of this study is to find out whether outpatient exercise rehabilitation, combined with psychological and motivational support, can improve fitness and quality of life for people living with pulmonary hypertension, particularly people whose pulmonary hypertension is secondary to heart or lung disease, because exercise rehabilitation has not been researched in these groups. The study will be run in specialist rehabilitation centres by staff experienced in treating people with heart and lung problems.

COVID-19 update (29/03/2021):
In light of the COVID-19 pandemic, exercise rehabilitation will move to an online home-based delivery model. We have drawn on existing resources and data from home-based rehabilitation programmes aimed at breathless, fatigued and anxious clinical populations, where data supports the potential efficacy of home-based vs centre-based programmes. SPHERe will now be resource-based (manual, online content) using functional (body weight or chair-based) exercise and a structured home-based exercise bike programme, remotely supervised and facilitated online by trained practitioners.

Who can participate?
Patients with pulmonary hypertension who live near one of at least 10 rehabilitation centres mainly in the East and West Midlands

What does the study involve?
Participants will be randomly allocated to either remotely supervised exercise with psychological and motivational support, or best-practice usual care (general physical activity advice). The 8-week intervention includes:
1. An online individual assessment and exercise familiarisation session
2. Once-weekly live online remotely supervised group home exercise programme
3. Twice-weekly guided home exercise bike and functional fitness programme
4. Weekly group online psychosocial and motivational support and education session (for 6 weeks).
People in the usual care group will receive a single (online) session of 1:1 advice on safe and effective lifestyle physical activity. A walking test and quality of life questionnaires will be used over 1 year to measure if the intervention can help people with pulmonary hypertension, and represents good value for the NHS.

What are the possible benefits and risks of participating?
This study may not offer people any direct benefit, but the results will help people with pulmonary hypertension in the future. If any of the assessments find anything unusual with participants’ health, they will receive prompt and appropriate medical care and attention. Exercise carries a very small risk of complications for people with pulmonary hypertension. If it is likely that certain people will have a problem during exercise, their medical team will not ask them to take part. For people who do take part, remote supervision will be provided by specialist staff. Exercise is likely to cause some tiredness, breathlessness and sore muscles, but this should get a bit easier over time. The researchers do not anticipate any serious risk to participants.

Where is the study run from?
University Hospitals Coventry & Warwickshire NHS Trust (UK)

When is the study starting and how long is it expected to run for?
June 2019 to August 2024

Who is funding the study?
Health Technology Assessment Programme (UK)

Who is the main contact?
Dr Gordon McGregor
gordon.mcgregor@uhcw.nhs.uk

Contact information

Dr Gordon McGregor
Scientific

University Hospital
Clifford Bridge Road
Coventry
CV22DX
United Kingdom

ORCID ID	0000-0001-8963-9107
Phone	+44 (0)2476234570
Email	gordon.mcgregor@uhcw.nhs.uk

Study information

Primary study design	Interventional
Study design	Randomized controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Supervised Pulmonary Hypertension Exercise REhabilitation (SPHERe): a multi-centre randomized controlled trial
Study acronym	SPHERe
Study objectives	The SPHERE intervention will improve clinical and patient-reported outcomes when compared to best practice usual care.
Ethics approval(s)	Approved 13/07/2019, West Midlands - Coventry & Warwickshire Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS; +44 (0)2071048101; nrescommittee.westmidlands-coventryandwarwick@nhs.net), REC ref: 19/WM/0155
Health condition(s) or problem(s) studied	Pulmonary hypertension
Intervention	Current interventions as of 29/03/2021: Participants will be randomly allocated to either remotely supervised exercise with psychological and motivational support, or best-practice usual care (general physical activity advice). The intervention group will be invited to complete 8 weeks of once-weekly remotely supervised exercise rehabilitation, alongside a home exercise bike programme (twice-weekly). The researchers have developed an exercise programme suitable for people with all types of pulmonary hypertension that can be delivered virtually from existing NHS exercise rehabilitation services. The study will be run from specialist rehabilitation centres by staff experienced in treating people with heart and lung problems. Weekly psychological and motivational support aims to reduce anxiety and improve exercise adherence. People in the usual care group will receive a single (online) session of 1:1 advice on safe and effective lifestyle physical activity, but not take part in the exercise programme. Previous interventions: Participants are randomly allocated to either supervised exercise with psychological and motivational support, or to continue with usual care (general physical activity advice). The intervention group will be invited to complete 8 weeks of twice-weekly supervised outpatient exercise rehabilitation. The researchers have developed an exercise programme suitable for people with all types of pulmonary hypertension that can be delivered within existing NHS exercise rehabilitation services. They have tested, evaluated, and refined this over a six-month period. The study will be run in specialist rehabilitation centres by staff experienced in treating people with heart and lung problems. Psychological and motivational support will help reduce anxiety and improve exercise adherence. People in the usual care group will receive general physical activity advice, but not supervised exercise.
Intervention type	Behavioural
Primary outcome measure(s)	Exercise capacity measured with incremental shuttle walk test (ISWT) at 4 months.
Key secondary outcome measure(s)	Current secondary outcome measures as of 24/02/2023: 1. Disease-specific health-related quality of life (HR-QoL) measured with Cambridge Pulmonary Hypertension Outcome Review at 4 and 12 months 2. Health utility measured with EQ-5D-5L at 4 and 12 months 3. Emotional well-being measured with the Hospital Anxiety and Depression Scale at 4 and 12 months 4. Generalised self-efficacy measured with a psychometric scale at 4 and 12 months 5. Fatigue measured with the Fatigue Severity Scale at 4 and 12 months 6. Functional status measured using WHO functional class at 4 and 12 months 7. Self-reported medication use at 4 and 12 months 8. Time to clinical worsening measured by medical notes and discussion with a clinician at 4 and 12 months 9. Health and social care resource use measured by participant self-report and NHS data at 4 and 12 months 10. All-cause hospital admissions from GP records at 12 months 11. Adverse events measured with NHS data at 4 and 12 months 12. All-cause mortality Previous secondary outcome measures as of 29/03/2021 to 24/02/2023: 1. Exercise capacity measured with incremental shuttle walk test at 12 months 2. Disease-specific health-related quality of life (HR-QoL) measured with Cambridge Pulmonary Hypertension Outcome Review at 4 and 12 months 3. Emotional well-being measured with the Hospital Anxiety and Depression Scale at 4 and 12 months 4. Self-efficacy measured with the Generalised self-efficacy scale at 4 and 12 months 5. Fatigue measured with the Fatigue Severity Scale at 4 and 12 months 6. Functional status measured using WHO functional class at 4 and 12 months 7. Self-reported medication use at 4 and 12 months 8. Time to clinical worsening measured by medical notes and discussion with clinician at 4 and 12 months 9. Hospital admissions measured with NHS data at 4 and 12 months 10. Adverse events measured with NHS data at 4 and 12 months 11. All-cause mortality measured with NHS data at 4 and 12 months 12. Heath utility measured with EQ-5D-5L at 4 and 12 months 13. Health and care resource use measured by participant self-report and NHS records at 4 and 12 months. Previous secondary outcome measures: 1. Exercise capacity measured with incremental shuttle walk test at 12 months 2. Exercise capacity measured with six-minute walk test at 4 and 12 months 3. Disease-specific health-related quality of life (HR-QoL) measured with Cambridge Pulmonary Hypertension Outcome Review at 4 and 12 months 4. Emotional well-being measured with the Hospital Anxiety and Depression Scale at 4 and 12 months 5. Self-efficacy measured with the Generalised self-efficacy scale at 4 and 12 months 6. Fatigue measured with the Fatigue Severity Scale at 4 and 12 months 7. Functional status measured using WHO functional class at 4 and 12 months 8. Medication use measured by self- report case report form at 4 and 12 months 9. Time to clinical worsening measured by medical notes and discussion with clinician at 4 and 12 months 10. Hospital admissions measured with NHS data at 4 and 12 months 11. Adverse events measured with NHS data at 4 and 12 months 12. All-cause mortality measured with NHS data at 4 and 12 months 13. Heath utility measured with EQ-5D-5L at 4 and 12 months 14. Health and care resource use measured by participant self-report and NHS records at 4 and 12 months
Completion date	31/08/2024

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	200
Total final enrolment	153
Key inclusion criteria	Current inclusion criteria as of 29/03/2021: 1. Adults with confirmed PH (groups 1 to 5) as detailed in ESC/ERS guidelines 2. Clinically stable 3. World Health Organisation (WHO) functional class II, III or IV 4. Fluent in spoken English to allow engagement with intervention and physical outcome measures 5. Live within reasonable travelling distance (as defined by the participant) of a SPHERE exercise rehabilitation centre (outcome assessments only) 6. Ability to provide informed consent 7. Access to appropriate IT infrastructure (computer, laptop, tablet, smart phone, email and internet connection) 8. Ability to make suitable travel arrangements to attend clinic (outcome assessments only) Previous inclusion criteria: 1. Adults with confirmed PH (groups 1 to 5) as detailed in ESC/ERS guidelines 2. Clinically stable 3. World Health Organisation (WHO) functional class II, III or IV 4. Fluent in spoken English to allow engagement with intervention and physical outcome measures 5. Live within reasonable travelling distance (as defined by the participant) of a SPHERE exercise rehabilitation centre 6. Ability to provide informed consent
Key exclusion criteria	Current exclusion criteria as of 29/03/2021: 1. Absolute contraindications to exercise as per international clinical guidelines 2. PH related complications, or comorbidities severe enough to prevent attendance at a SPHERE centre, or participation in exercise rehabilitation 3. Any mental health issue that will prevent engagement with study procedures 4. Previous randomisation in the present trial 5. Pregnancy at the time of recruitment Previous exclusion criteria: 1. Absolute contraindications to exercise as per international clinical guidelines 2. PH related complications, or comorbidities severe enough to prevent attendance at a SPHERE centre, or participation in exercise rehabilitation 3. Any mental health issue that will prevent engagement with study procedures 4. Unable to make suitable travel arrangements 5. Previous randomisation in the present trial 6. Pregnancy
Date of first enrolment	16/06/2021
Date of final enrolment	31/08/2023

Locations

Countries of recruitment

United Kingdom
England
Scotland
Wales

Study participating centres

University Hospitals Coventry & Warwickshire NHS Trust

Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Walsall Healthcare NHS Trust

Manor Hospital
Moat Road
Walsall
WS2 9PS
United Kingdom

Royal United Hospitals Bath NHS Foundation Trust

Combe Park
Bath
BA1 3NG
United Kingdom

University Hospitals Birmingham NHS Foundation Trust

Queen Elizabeth Hospital
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom

Broomfield Hospital

Court Road
Broomfield
Chelmsford
CM1 7ET
United Kingdom

Golden Jubilee National Hospital

Agamemnon Street
Clydebank
G81 4DY
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study will be available upon request after publication of the main study results. Requests for data sharing will be managed in accordance with University of Warwick policy on data sharing.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	19/05/2020	26/05/2020	Yes	No
Protocol article	Protocol update	20/07/2024	22/07/2024	Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Statistical Analysis Plan	version 1.1	01/05/2024	12/07/2024	No	No
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN10608766 SPHERe Statistical and Health Economics Analysis Plan_v1.1 01May2024.pdf: Statistical Analysis Plan

Editorial Notes

22/07/2024: Publication reference added.
12/07/2024: The statistical analysis plan was uploaded as an additional file.
01/03/2024: Total final enrolment added. The intention to publish date was changed from 28/03/2024 to 31/03/2025.
16/08/2023: The following changes have been made:
1. The recruitment end date was changed from 31/03/2023 to 31/08/2023.
2. The overall study end date has been changed from 29/02/2024 to 31/08/2024 and the plain English summary has been updated to reflect this change.
24/02/2023: The following changes have been made:
1. The overall trial end date has been changed from 30/11/2023 to 29/02/2024 and the plain English summary has been updated to reflect this change.
2. The secondary outcome measures have been changed.
3. Patient information sheet added.
4. The target number of participants has been changed from 352 to 200.
5. The recruitment start date has been changed from 01/09/2019 to 16/06/2021.
6. The recruitment end date has been changed from 30/11/2022 to 31/03/2023.
7. Scotland and Wales were added as countries of recruitment.
8. Walsall Healthcare NHS Trust, Royal United Hospitals Bath NHS Foundation Trust, University Hospitals Birmingham NHS Foundation Trust, Broomfield Hospital and Golden Jubilee National Hospital were added as trial participating centres.
05/04/2022: The following changes have been made:
1. The recruitment end date has been changed from 30/04/2022 to 30/11/2022.
2. The overall trial end date has been changed from 31/08/2022 to 30/11/2023 and the plain English summary has been updated to reflect this change.
3. The intention to publish date has been changed from 31/08/2023 to 28/03/2024.
29/03/2021: The following changes were made to the trial record:
1. The interventions, secondary outcome measures, inclusion and exclusion criteria and plain English summary were updated.
2. The trial website was added.
3. Recruitment to this study is no longer paused.
26/05/2020: Publication reference added.
27/04/2020: Due to current public health guidance, recruitment for this study has been paused.
30/07/2019: The ethics approval was added.
18/03/2019: Trial's existence confirmed by the NIHR HTA.