Effect of Exercise Training in Patients With Pulmonary Hypertension

Study Overview
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Brief Summary
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Pulmonary Hypertension (PH) is a serious disease with a dismal prognosis when left untreated. Advances in medical therapy have improved survival according to recent registries and systematic reviews, but are associated with high healthcare costs. Earlier studies in Heidelberg, Germany showed good evidence for the effect of exercise training on improving exercise performance, quality of life and pulmonary hemodynamics in patients with pulmonary hypertension. The main objectives of the present project are: to investigate the quality of the implementation of a standardized 3 week in-hospital exercise training program on markers of outcome and disease severity in PH-patients in Switzerland immediately after training and after 3 and 12 month. to look whether training with hyperoxia vs. standard care might be more effective. This is a multicentre, randomized parallel-group trial where the intervention rehabilitation is delayed in one group so that they can serve as standard care controls for the others. In a nested single-centre randomized-controlled trial patent will additionally be randomized to receive either usual rehabilitation (UR) or rehabilitation with standardized supplemental oxygen therapy (SSOT) during nights and ergometer training. Patients will receive a PH specific rehabilitation program during 3 weeks followed by an instructed home-based training program for 12 weeks. Patients who are not already under long-term oxygen therapy (LTOT) due to daytime hypoxemia will additionally be randomized to receive standardized supplemental oxygen therapy (SSOT) during training and nights upon written informed consent.

Official Title
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Effect of Exercise Training in Arterial and Chronic Thromboembolic Pulmonary Hypertension in Switzerland and Standardization With European Countries

Conditions
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Hypertension, Pulmonary

Intervention / Treatment
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* Behavioral: respiratory and exercise therapy
* Behavioral: respiratory and exercise therapy with supplemental oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: WHO functional class II-IV PH diagnosed by right heart catheter showing: Baseline mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg Baseline pulmonary vascular resistance (PVR) > 240 dyn x s x cm-5 Baseline pulmonary capillary wedge pressure (PCWP) ≤ 15 mm Hg Patients receiving maximal PH therapy including intensified treatment with diuretics and who have been stable for 2 months before entering the study PH target therapy should not be expected to change during the entire 15-week study period Negative pregnancy test (β-HCG) at the start of the trial Able to understand and willing to sign the Informed Consent Form Exclusion Criteria: PH due to significant left heart disease (Wedge ≥ 15mmHg) or lung disease (FEV1 ≤ 60% predicted) Pregnancy at study onset Walking disability Any change in disease-targeted therapy within the last 2 months Any subject who is scheduled to receive another investigational drug during the course of this study Any other relevant concomitant disease Systolic blood pressure < 85 mmHg History or suspicion of inability to cooperate adequately

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immediate Rehabilitation<br>The PH specific rehabilitation consists of: bicycle ergometer training, respiratory training, dumbbell-training and (mental) gait training. | Behavioral: respiratory and exercise therapy<br>* The PH specific rehabilitation consists of: bicycle ergometer training, respiratory training, dumbbell-training and (mental) gait training.<br>|
| Experimental: Immediate Rehabilitation with oxygen<br>The PH specific rehabilitation consists of: bicycle ergometer training, respiratory training, dumbbell-training and (mental) gait training. Patients who are not already under long-term oxygen therapy (LTOT) due to daytime hypoxemia will additionally be randomized to receive standardized supplemental oxygen therapy (SSOT) during training and nights. | Behavioral: respiratory and exercise therapy with supplemental oxygen<br>* The PH specific rehabilitation consists of: bicycle ergometer training, respiratory training, dumbbell-training and (mental) gait training. Patients who are not already under long-term oxygen therapy (LTOT) due to daytime hypoxemia will additionally be randomized to receive standardized supplemental oxygen therapy (SSOT) during training and nights.<br>|
| Experimental: Delayed Rehabilitation<br>Waiting group that participates in the rehabilitation program after 3 months. The PH specific rehabilitation consists of: bicycle ergometer training, respiratory training, dumbbell-training and (mental) gait training. | Behavioral: respiratory and exercise therapy<br>* The PH specific rehabilitation consists of: bicycle ergometer training, respiratory training, dumbbell-training and (mental) gait training.<br>|
| Experimental: Delayed Rehabilitation with oxygen<br>Waiting group that participates in the rehabilitation program after 3 months. The PH specific rehabilitation consists of: bicycle ergometer training, respiratory training, dumbbell-training and (mental) gait training. Patients who are not already under long-term oxygen therapy (LTOT) due to daytime hypoxemia will additionally be randomized to receive standardized supplemental oxygen therapy (SSOT) during training and nights. | Behavioral: respiratory and exercise therapy with supplemental oxygen<br>* The PH specific rehabilitation consists of: bicycle ergometer training, respiratory training, dumbbell-training and (mental) gait training. Patients who are not already under long-term oxygen therapy (LTOT) due to daytime hypoxemia will additionally be randomized to receive standardized supplemental oxygen therapy (SSOT) during training and nights.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Minute walking test |  | Change from Baseline to 15 weeks | 
| Constant cardiopulmonary exercise testing change in endurance time |  | Change from Baseline to 15 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life (questionnaire) | Minnesota living with heart failure questionnaire, Camphor, short form 36 item | Baseline, 3 weeks, 15 weeks, 6 and 12 months | 
| Sit-to-Stand (physiological parameter) | Number of Sit-to-Stand performed in 1 minute | Baseline, 3 weeks, 15 weeks, 6 and 12 months | 
| Stair Ascent (physiological parameter) | Force, Power and Time needed to climb 5 steps | Baseline, 3 weeks, 15 weeks, 6 and 12 months | 
| Cognitive function (questionnaire) | Trail Making Test A & B, Stroop 1-3, 5 point test | Baseline, 3 weeks, 15 weeks, 6 and 12 months | 
| Hemodynamic (physiological parameter) | Pulmonary artery pressure, cardiac output | Baseline, 3 weeks, 15 weeks, 6 and 12 months | 
| Functional class (scale) |  | Baseline, 3 weeks, 15 weeks, 6 and 12 months | 
| Lung function (physiological parameter) | Forced vital capacity and liters in 1 second, Total lung capacity, diffusion of carbon dioxide | Baseline, 3 weeks, 15 weeks, 6 and 12 months | 
| Daily activity (energy expenditure, steps per day, sleep time and efficiency, lying down time, physical activity level, metabolic equivalent units) | Actigraphy | Baseline, 3 weeks, 15 weeks, 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary arterial hypertension, Chronic thromboembolic pulmonary hypertension, Rehabilitation, Oxygen