Implementation and effect of exercise and respiratory training on 6-minute walking distance in patients with severe chronic pulmonary hypertension: a randomized controlled multicenter trial in European countries

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 10

Inclusion Criteria

1. Female and male patients of any ethnic origin *18 years
2. WHO functional class II-IV
3. 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 mmHg
4. Patients receiving optimized conventional PH therapy including intensified treatment with diuretics and who have been stable for 2 months before entering the study.
5. Except for diuretics, medical treatment should not be expected to change during the entire 15-week study period.
6. Negative pregnancy test (*-HCG) at the start of the trial and appropriate contraception throughout the study for women with child-bearing potential.
7. Able to understand and willing to sign the Informed Consent Form

Exclusion Criteria

1. PH of any cause other than permitted in the entry criteria, e.g. concomitantly to portal hypertension, complex congenital heart disease, reversed shunt, HIV infection, suspected pulmonary veno-occlusive disease based on pulmonary edema during a previous vasoreactivity test or on abnormal findings compatible with this diagnosis (septal lines or pulmonary edema at high resolution computer tomography), congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension or unclear diagnosis
2. Pregnancy
3. Patients with signs of right heart decompensation
4. Walking disability
5. Acute infection
6. Pyrexia
7. Any change in disease-targeted therapy within the last 2 months
8. Any subject who is scheduled to receive an investigational drug during the course of this study
9. Severe lung disease: FEV1/FVC <0.5 and total lung capacity <70% of the normal value
10. Active myocarditis, instable angina pectoris, exercise induced ventricular arrhythmias, decompensated heart failure, active liver disease, porphyria or elevations of serum transaminases >3 x ULN (upper limit of normal) or bilirubin >1.5 x ULN
11. Hemoglobin concentration of less than 75% of the lower limit of normal
12. Systolic blood pressure <85 mmHg
13. History or suspicion of inability to cooperate adequately.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Study Objective<br /><br>To investigate the effect of exercise training on 6-MWD in a multicenter<br /><br>setting and implement a low-dose, closely supervised training program for<br /><br>patients with pulmonary hypertension in European countries.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary Objectives<br /><br>Investigate the effect on WHO functional class, quality of life,<br /><br>echocardiographic parameters, cardiopulmonary exercise testing, laboratory<br /><br>parameters such as inflammatory markers, markers for right heart impairment,<br /><br>safety parameters and optional assessment of epigenetic changes. Further<br /><br>effects on lung function/blood gases, safety parameters, adverse events and<br /><br>survival will be analyzed. Optionally, MRI parameters and DNA variations will<br /><br>be assessed to investigate effects of DNA mutations on treatment effects.</p><br>