Pulmonary Rehabilitation to Improve Physical Capacity After Pulmonary Embolism

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Pulmonary Embolism
• Intervention / Treatment: Other: Rehabilitation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Grålum, Norway, 1714
    • The hospital of Østfold, Kalnes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rehabilitation; Physiotherapist-supervised outpatient rehabilitation program 2 times a week for a total of 8 weeks.	Other: Rehabilitation; Rehabilitation
No Intervention: No rehabilitation; Patients will receive usual care, including information pamphlets with information on the disease and the general importance of exercise.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial fibrosis evaluated by cardiac MRI	The primary objective in the pathophysiology part of the study is to investigate whether diffuse myocardial fibrosis shown by CMR is associated with PPS	At baseline

Collaborators and Investigators

• Sponsor: Ostfold Hospital Trust
• Collaborators: Ullevaal University Hospital; University Hospital, Akershus
• Investigators: Study Director: Waleed Ghanima, MD. Assoc.Prof, Hospital of Østfold, Kalnes

Publications and helpful links

General Publications

• Fabyan KD, Holley AB. Postpulmonary embolism syndrome. Curr Opin Pulm Med. 2021 Sep 1;27(5):335-341. doi: 10.1097/MCP.0000000000000789.
• Haukeland-Parker S, Jervan O, Johannessen HH, Gleditsch J, Stavem K, Steine K, Spruit MA, Holst R, Tavoly M, Klok FA, Ghanima W. Pulmonary rehabilitation to improve physical capacity, dyspnea, and quality of life following pulmonary embolism (the PeRehab study): study protocol for a two-center randomized controlled trial. Trials. 2021 Jan 6;22(1):22. doi: 10.1186/s13063-020-04940-9.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2018
• Primary Completion (Actual): August 30, 2022
• Study Completion (Estimated): March 30, 2024

Study Registration Dates

• First Submitted: January 11, 2018
• First Submitted That Met QC Criteria: January 19, 2018
• First Posted (Actual): January 23, 2018

Study Record Updates

• Last Update Posted (Actual): November 3, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Rehabilitation; Pulmonary embolism; PPS; Dyspnea; Post Pulmonary Embolism Syndrome; Cardiac magnetic resonance imaging (CMR)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pulmonary Embolism
• Other Study ID Numbers: 2017/1940 (REK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No