Pulmonary Rehabilitation to Improve Physical Capacity After Pulmonary Embolism

Study Overview
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Brief Summary
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This project aims to evaluate a rehabilitation program as treatment and uncover potential pathophysiological mechanisms of a newly identified chronic condition named Post Pulmonary Embolism Syndrome (PPS).

Detailed Description
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The newly identified Post Pulmonary Embolism Syndrome (PPS) is characterized by chronic persistent, but unexplained dyspnea (i.e. without signs of pulmonary hypertension or pulmonary abnormality). Symptoms are considerable, but less severe than in CTEPH patients. A recent study performed by our group confirmed that up to 50% of our patients complained of various grades of persistent unexplained dyspnea 1-10 years after the diagnosis of PE. In this multifaceted project we wish to evaluate the effect of an eight week rehabilitation program led and supervised by a trained physiotherapist on exercise capacity in PPS patients. This interventional part of the study will be formed as a randomized controlled trial. Patients will be randomized to either usual care or a physiotherapist-supervised rehabilitation program. The study also aims to explore potential underlying pathophysiological mechanisms in PPS, using state of the art methods such as cardiac magnetic resonance imaging and transthoracic echocardiography involving novel methods focusing on the right ventricle. The pathophysiological part of the study will be formed as a case control study, where post PE-patients who do not fulfill the criteria for PPS will serve as controls.

Official Title
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Pulmonary Rehabilitation to Improve Physical Capacity After Pulmonary Embolism - a Randomized Controlled Trial - The REHAB Study

Conditions
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Pulmonary Embolism

Intervention / Treatment
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* Other: Rehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Objectively diagnosed symptomatic pulmonary embolism by CTPA or high-probability scintigraphy 6 months to 6 years before inclusion Persistent dyspnea defined as modified Medical Research Council (mMRC) breathlessness scale >= 1 that has appeared or worsened after the diagnosis of PE (eligibility criteria for randomization) Exclusion Criteria: Significant pulmonary disease (COPD GOLD >= 2, restrictive pulmonary disease, lung cancer or pleural disease. Heart failure (either HFrEF, HFmrEF or HFpEF as defined in ESC guidelines) Significant valvular heart disease Chronic thromboemboli pulmonary hypertension (CTEPH) Patients unfit for rehabilitation or walking tests du to old age, physical disability or disease Patients with a history of poor compliance or any condition that would interfere with the ability to comply with the study protocol e.g. history of drug abuse, excessive alcohol beverage consumption, cognitive dysfunction or severe psychiatric disease Active malignancy Life expectancy less than 3 months Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Rehabilitation<br>Physiotherapist-supervised outpatient rehabilitation program 2 times a week for a total of 8 weeks. | Other: Rehabilitation<br>* Rehabilitation<br>|
| No Intervention: No rehabilitation<br>Patients will receive usual care, including information pamphlets with information on the disease and the general importance of exercise. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ISWT | Change in Incremental Shuttle Walk Test will be primary endpoint for interventional part of the study | ISWT wil be performed at 12 weeks and 36 weeks after baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mMRC | The effect of rehabilitation on dyspnea measured by mMRC breathlessness scale | 12 weeks and 36 weeks after inclusion | 
| Sensewear | The effect of PRP on daily physical activity as measured with an activity monitor (Sensewear) | 12 weeks and 36 weeks after baseline | 
| HRQoL by EQ-5d | The effect of rehabilitation on HRQoL measured by EQ-5D | 12 weeks and 36 weeks after baseline | 
| HRQoL by PEmb-QoL | The effect of rehabilitation on HRQoL measured by PEmb-QoL | 12 weeks and 36 weeks after baseline | 
| Long term effect of physical capacity | The long-term effect of rehabilitation on physical capacity measured by ISWT, 6 months after completing the rehabilitation | 6 months after completing rehabilitation | 
| Test-retest reliability of the ISWT in this patient population | Test-retest reliability of the ISWT in this patient population | At baseline, 12 weeks and 36 weeks | 
| Minimum clinically important difference for ISWT | Establish the minimum clinically important difference (MID) for the ISWT in patients with PPS expressed in meters. | 36 weeks after baseline | 
| Proportion of patients who achieves the established minimum clinically important difference | Proportion of patients who achieves the established minimum clinically important difference for ISWT for this population | 36 weeks after baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary embolism, Dyspnea, Post Pulmonary Embolism Syndrome, PPS, Rehabilitation, Cardiac magnetic resonance imaging (CMR)