Impact on Quality of Life With Pulmonary RehAbilitation After Pulmonary eMBOlism: RAMBO Study (RAMBO)

Pulmonary Embolism (PE) is a common and serious disease. Indeed, the annual incidence is 1/1000 patients per year and the 3-month mortality is 10%, which is twice that of myocardial infarction. The treatment is based on anticoagulation for at least 3 months. However, after three or six months of anticoagulation, persistent dyspnea and impairment of quality of life are observed in at least 30% of cases. Several mechanisms explain dyspnea and impairment of quality of life after PE, such as residual pulmonary artery obstruction, exercise deconditioning, depressive syndrome or development of a cardio-respiratory pathology. Pulmonary rehabilitation (PR) has been shown to be effective on dyspnea and quality of life and is included in the therapeutic management of chronic respiratory diseases such as Chronic Obstructive Pulmonary Disease (COPD) or pulmonary fibrosis. Furthermore, PR is also used after a myocardial infarction. However, PR after PE is still not included in therapeutic management of PE while outpatient management is recommended for the majority of patients after an acute PE episode. Study hypothesis is that PR has the potential to improve quality of life and dyspnea perception in patients who have received anticoagulation for at least 3 months after PE and who present an impairment of quality of life and/or a persistent dyspnea. This study presents several innovative aspects. First, to our knowledge, This study is the first large randomized trial assessing PR at least 3 months after acute symptomatic PE. Only one small randomized trial on 18 patients evaluating the impact of PR after PE has been published; as PR was performed just after the acute phase of PE in this trial, the clinical status improvement observed in this study could not be explained by PR alone, but also by anticoagulation. In this study, the investigators will include 112 patients at least 3 months after PE in order to exclude the bias related to anticoagulation effect. Second, This study is the first large randomized trial. Third, this study is the first that have the potential to demonstrate efficacy and safety of delayed PR after PE in patients with impaired quality of life due to persistent residual dyspnea.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Embolism; Quality of Life and Dyspnea
• Intervention / Treatment: Other: Pulmonary rehabilitation (PR)

• Study Type: Interventional
• Enrollment (Estimated): 112
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cécile TROMEUR, PH; Phone Number: +33230337602; Email: cecile.tromeur@chu-brest.fr

Study Locations

• France
  • Angers, France, 49100
    • Not yet recruiting
    • CHU Angers
    • Contact: Frédéric GAGNADOUX, PU-PH
    • Principal Investigator: Frédéric GAGNADOUX, PU-PH
  • Brest, France, 29609
    • Recruiting
    • CHU Brest
    • Contact: Cécile TROMEUR, PH
    • Principal Investigator: Cécile TROMEUR, PH
    • Sub-Investigator: Francis COUTURAUD, PU-PH
    • Sub-Investigator: Aude BARNIER, PH
    • Sub-Investigator: Christophe GUT-GOBERT, PH
    • Sub-Investigator: Cécile L'HEVEDER, PH
    • Sub-Investigator: Christophe LEROYER, PU-PH
    • Sub-Investigator: Alexandre FAUCHE, PH
    • Sub-Investigator: Raphael LE MAO, PH
  • Lorient, France, 56100
    • Not yet recruiting
    • CHBS Lorient
    • Contact: Mikael LE HENAFF, PH
    • Principal Investigator: Mikael LE HENAFF, PH
  • Morlaix, France, 29672
    • Not yet recruiting
    • CH Morlaix
    • Contact: Catherine LE BER, PH
    • Principal Investigator: Catherine LE BER, PH
  • Paris, France, 75015
    • Not yet recruiting
    • Hegp (Ap-Hp)
    • Contact: Benjamin PLANQUETTE, PH
    • Principal Investigator: Benjamin PLANQUETTE, PH
  • Roscoff, France, 29684
    • Not yet recruiting
    • Centre de santé de Roscoff
    • Contact: Sophie RAMEL, PH
    • Principal Investigator: Sophie RAMEL, PH
  • Saint-Etienne, France, 42055
    • Not yet recruiting
    • CHU Saint-Etienne
    • Contact: Laurent BERTOLETTI, PU-PH
    • Principal Investigator: Laurent BERTOLETTI, PU-PH
  • Tours, France
    • Not yet recruiting
    • Chu Tours
    • Contact: Denis ANGOULVANT, PH
    • Principal Investigator: Denis ANGOULVANT, PU-PH

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years
• Patient treated with at least 3 months and up to 8 months of anticoagulation for symptomatic EP diagnosed according the ESC and ACCP guidelines.
• Patients who have a PembQol score ≥ 10% and whose total scores for the subgroups Q7+8 (dyspnea) and Q4 (impact of daily life) are ≥ 10%.

Exclusion Criteria:

• Presence of CTEPH according to international guidelines
• Patients treated for acute PE with anticoagulants for more than 8 months
• Active cancer or in remission for less than two years
• Dyspnea post - COVID due to parenchymal injuries
• Post-COVID hyperventilation syndrome without pulmonary vascular perfusion sequelae.
• Physical or psychological inability to undertake PR
• Isolated or more distal segmental PE
• Neuro-muscular disease with PR contraindication.
• Cardiac insufficiency (unstable coronary artery disease)
• Severe respiratory failure (long-term oxygen therapy, pulmonary hypertension)
• Chronic dyspnea MMRC ≥ 2 before PE
• Cardiac or respiratory rehabilitation in the previous year
• Indication to urgent PR within 6 months at the time of inclusion
• Life expectancy of less than 12 months
• Inability to give consent
• Patient under guardianship or curatorship
• Patient deprived of liberty by an administrative or judicial decision
• Patient has not social security affiliation or who don't beneficiary of such social security

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; 20 sessions of Pulmonary rehabilitation will be performed over a period of 3 months	Other: Pulmonary rehabilitation (PR); 20 sessions of PR in respiratory rehabilitation centre will be performed over a period of 3 months
No Intervention: Control group; No Pulmonary rehabilitation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life - PEmbQoL score	Pulmonary embolism Quality of life score. This score includes 6 items regarding the frequency of lung complaints, their intensity, their physical, personal, social and professional impact. For each item, an average score is collected	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety : number and type of adverse reactions	Number of events	3 months
Quality of life - PEmbQoL score	Pulmonary embolism Quality of life score. This score includes 6 items regarding the frequency of lung complaints, their intensity, their physical, personal, social and professional impact. For each item, an average score is collected	15 months
Pulmonary Vascular Obstruction index	Pulmonary Vascular Obstruction (Meyer score) assessed with V/Q lung scan	3 months
Incidence of dyspnea	Multidimensional dyspnea Profile (MDP) at the cycloergometer, Borg scale at the cycloergometer and at the 6 minute-walk-test, and Modified Medical Research Council scale (MMRC)	3 months and 15 months
Change of 6 Minutes Walk Test	6 Minutes Walk Test	3 months and 15 months
Change of Psychological status	Score of Hospital Anxiety and Depression scale. 14 rated items from 0 to 3. Seven questions relate to anxiety (total A) and seven others to the depressive dimension (total D), allowing thus obtaining two scores (maximum score for each score = 21)	3 months and 15 months
Symptomatic recurrent PE	Number of events	15 months
Arterial thromboembolic events	Number of events	15 months
Deaths of all causes	Number of events	15 months
Hospitalizations and acute medical events	Number of events	15 months

Collaborators and Investigators

• Sponsor: University Hospital, Brest

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2022
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: August 11, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (Actual): August 20, 2021

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Embolism and Thrombosis; Signs and Symptoms, Respiratory; Embolism; Pulmonary Embolism; Dyspnea
• Other Study ID Numbers: 29BRC21.0093 (RAMBO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected data that underlie results in a publication
• IPD Sharing Time Frame: Data will be available beginning five years and ending fifteen years following the final study report completion
• IPD Sharing Access Criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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