Title: Supervised Pulmonary Hypertension Exercise Rehabilitation (SPHERe) trial
Funder: Department of Health and Social Care

Abstract: Why is this important?_x000D_ 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._x000D_ _x000D_ 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 out-patient service, typically lasting an hour, twice a week for eight weeks. We do not know if out-patient exercise rehabilitation can help improve the lives of people with pulmonary hypertension._x000D_ _x000D_ What are we trying to find out? _x000D_ We want to know if out-patient exercise rehabilitation, combined with psychological and motivational support, can improve fitness and quality of life for people living with pulmonary hypertension. We are particularly interested in people whose pulmonary hypertension is secondary to heart or lung disease, because exercise rehabilitation has not been researched in these groups. We will enrol 350 people with pulmonary hypertension who live near one of 11 rehabilitation centres in the East and West Midlands, and who agree to be randomly allocated to supervised exercise with psychological and motivational support, or to continue with usual care (general physical activity advice)._x000D_ _x000D_ What treatments are we testing?_x000D_ The intervention group will be invited to complete eight weeks of twice-weekly supervised out-patient exercise rehabilitation. We have developed an exercise programme suitable for people with all types of pulmonary hypertension that can be delivered within existing NHS exercise rehabilitation services. We 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._x000D_ _x000D_ How will we know if the treatment helps?_x000D_ From talking to people with pulmonary hypertension, we know that the most important benefit of any treatment is reduced breathlessness and fatigue. People have told us that this would reduce anxiety about daily activities, helping them to ‘do more’, walk further and have a better quality of life. We will use a walking test and quality of life questionnaires over one year to measure if our intervention helps people with pulmonary hypertension, and represents good value for the NHS

Lay abstract: Why is this important?_x000D_ 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._x000D_ _x000D_ Background: Pulmonary hypertension (PH) is a debilitating condition, causing dyspnoea, fatigue, dizziness, and chest pain. Many affected people are anxious about, and avoid, physical activity. Depression is common, and quality of life can be poor. Supervised exercise rehabilitation may be safe and beneficial for people with PH groups 1 (pulmonary vascular disease) and 4 (chronic thromboembolic disease), particularly as an in-patient. It has not been tested in the most common groups; group 2 (left heart disease) and group 3 (lung disease), or group 5 (miscellaneous disorders); and has not been evaluated in an NHS out-patient setting, or with long-term follow-up._x000D_ _x000D_ Design/setting: Stage 1: pre-pilot with 6-10 participants at 3 centers, to confirm feasibility. Stage 2: 6-month internal pilot (n=60) to confirm recruitment and retention at multiple centres. Stage 3: multi-centre, two-arm RCT with parallel process evaluation and 1.15:1 treatment allocation, randomised by minimisation based on PH group, WHO functional class, and centre (11 NHS out-patient centres in the East and West Midlands)._x000D_ _x000D_ Population: Adults with confirmed PH diagnosis (groups 1-5) as per ESC/ERS guidelines, WHO functional class II-IV, and clinically stable. Exclusion: unable/unsafe to exercise or travel to a treatment centre, PH related hospital admission in last 4 weeks._x000D_ _x000D_ Health technology: The 8-week Supervised Pulmonary Hypertension Exercise Rehabilitation (SPHERe) intervention, developed through systematic literature review, expert opinion, stakeholder consensus, and component piloting. SPHERe includes: 1) individual assessment and familiarisation sessions; 2) supervised out-patient exercise programme; 3) psychosocial/motivational support and education; 4) guided home exercise plan._x000D_ _x000D_ Control: Best practice usual care with a one-to-one practitioner appointment, and general advice on safe and effective physical activity._x000D_ _x000D_ Primary outcome: Incremental Shuttle Walk Test at 4 months. Measured by researchers blinded to treatment allocation at baseline, 4 months (post-intervention) and 12 months. Secondary outcomes: exercise capacity, quality of life, health utility, anxiety/depression, self-efficacy, fatigue, WHO functional class, medication use, time to clinical worsening, health and social care use, all-cause hospital admissions and mortality, adverse events._x000D_ _x000D_ Sample size: Allowing for 20% loss to follow-up, 352 participants are required to achieve 90% power at 5% significance level; based on a SMD of 0.5 (45m in 6MWT), an ICC of 0.03, and an intervention group cluster size of 12 at follow-up._x000D_ _x000D_ Analysis. Primary: overall treatment effect for all PH diagnostic groups. Secondary: pooled effects for groups 2 and 3. We will use intention-to-treat analyses and hierarchical linear regression models to estimate treatment effects (95% confidence intervals), adjusted for patient-level covariates and centre effect. Prospective cost-effectiveness will be assessed as incremental cost per QALY estimates and credible intervals, cost-effectiveness acceptability curve and value-of-information analyses._x000D_ _x000D_ Team: Lay partners, clinical academic exercise physiology, physiotherapy, health psychology, secondary care medicine (cardiology and respiratory), general practice, statistics, health economics, clinical trialists._x000D_ _x000D_ Timeline (month): Set-up, pre-pilot and internal pilot (0-9); recruitment (4-23); primary outcome follow-up (8-27); 12-month follow-up (16-35) analysis/dissemination (35-39); 5-year follow-up (27-83).

Research activity codes: 6.7 PHYSICAL
Health categories: CARDIOVASCULAR