Effect of Exercise Training in Patients With Pulmonary Hypertension

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

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:

1. 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.
2. 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.

Study Overview

• Status: Recruiting
• Conditions: Hypertension, Pulmonary
• Intervention / Treatment: Behavioral: respiratory and exercise therapy; Behavioral: respiratory and exercise therapy with supplemental oxygen

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Silvia Ulrich Somaini, PD Dr.; Phone Number: 0041442552220; Email: silvia.ulrich@usz.ch
• Study Contact Backup: Name: Stéphanie Saxer, MSc; Phone Number: 0041442552220; Email: stephanie.saxer@usz.ch

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • Recruiting
    • UniversityHospital Zurich, Department of Pulmonology
    • Contact: Silvia Ulrich Somaini, PD Dr.; Phone Number: 0041442552220; Email: silvia.ulrich@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immediate Rehabilitation; The PH specific rehabilitation consists of: bicycle ergometer training, respiratory training, dumbbell-training and (mental) gait training.	Behavioral: respiratory and exercise therapy; The PH specific rehabilitation consists of: bicycle ergometer training, respiratory training, dumbbell-training and (mental) gait training.
Experimental: Immediate Rehabilitation with oxygen; 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; 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.
Experimental: Delayed Rehabilitation; 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; The PH specific rehabilitation consists of: bicycle ergometer training, respiratory training, dumbbell-training and (mental) gait training.
Experimental: Delayed Rehabilitation with oxygen; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
Hospitalisation days	Baseline, 3 weeks, 15 weeks, 6 and 12 months

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Silvia Ulrich Somaini, PD Dr., UniversityHospital Zurich

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: September 14, 2015
• First Submitted That Met QC Criteria: September 21, 2015
• First Posted (Estimate): September 24, 2015

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: November 1, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Rehabilitation; Pulmonary arterial hypertension; Oxygen; Chronic thromboembolic pulmonary hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: KEK-ZH-Nr. 2015-0231