Early Exercise-Based Rehabilitation in Patients Hospitalized for Acute Pulmonary Embolism

Official title

Early Exercise-based Rehabilitation in High-risk Patients Hospitalized for Acute Pulmonary Embolism: a Pragmatic Multicenter Randomized Partially Blinded Superiority Trial

Overview

Up to half of patients with pulmonary embolism (PE) suffer from impaired quality of life, reduced physical capacity, and symptoms like shortness of breath even three months after diagnosis, despite standard treatment with anticoagulation (blood thinners). The randomized RehabPE trial investigates whether an early, structured rehabilitation program with physical training and patient education can prevent such long-term effects. The study includes hospitalized patients with acute symptomatic PE who are at increased risk of impaired quality of life three months after diagnosis. After informed consent, patients are randomly assigned to one of two groups: one receives an early 6-8-week, center-based rehabilitation program; the other receives standard follow-up care without rehabilitation. The intervention group completes 16-18 outpatient sessions of endurance and strength training, along with two education sessions covering the condition, treatment, and symptom management. Over 180 days, changes in quality of life, physical exercise capacity, breathlessness, and psychological symptoms, and the time to return to work / usual daily activities will be monitored and compared between groups.

Interventions

• Other Exercise-based rehabilitation program
  Participants in the intervention group will receive a patient-tailored early (i.e., within 4 weeks of PE diagnosis) EBR program, comprising 16-18 sessions of supervised aerobic exercise and resistance/strength training at local outpatient rehabilitation centers, along with 2 PE-related educational sessions at 2 and 6 weeks of rehabilitation. Participants will receive comprehensive information on the purpose of EBR and each of its components, reassurance on its safety, and education on self-monit

Primary outcome measures

• Change in generic health-related quality of life (Physical Component Summary score; SF-36) [Time frame: From baseline to day 90 after randomization]

Secondary outcome measures (9)

• Change in generic health-related quality of life (Physical Component Summary score; SF-36) [Time frame: From baseline to day 180 after randomization]
• Change in generic health-related quality of life (Mental Component Summary score; SF-36) [Time frame: From baseline to day 90 and to day 180 after randomization]
• Change in PE-specific health-related quality of life (PEmb-QoL) [Time frame: From baseline to day 90 and to day 180 after randomization]
• Change in physical exercise capacity (6 minute walking test) [Time frame: From baseline to day 90 and to day 180 after randomization]
• Change in functional status (Post-VTE Functional Status) [Time frame: From baseline to day 90 and to day 180 after randomization]
• Time to return to work (workers) or usual activities of daily living (non-workers) [Time frame: For the duration of the study: 180 days]
• Change in dyspnea [Time frame: From baseline to day 90 and to day 180 after randomization]
• Change in symptoms of anxiety (GAD-7) [Time frame: From baseline to day 90 and to day 180 after randomization]
• Change in symptoms of depression (PHQ-9) [Time frame: From baseline to day 90 and to day 180 after randomization]

Eligibility criteria

Inclusion criteria

• Age ≥18 years
• Hospitalization for objectively confirmed acute symptomatic PE, defined as intraluminal filling defect of a segmental or more proximal pulmonary artery on computed tomography pulmonary angiography (CTPA) or a high-probability ventilation-perfusion scintigraphy, and admission within the past 7 days
• Increased risk for post-PE syndrome, defined as simplified Pulmonary Embolism Severity Index (sPESI) ≥1 point at the time of admission
• Written informed consent

Exclusion criteria

• Contraindication to EBR (known unstable cardiac conditions like angina pectoris, severe valvular heart disease, or severe resting pulmonary hypertension)
• Medical condition that clearly precludes participation in EBR (e.g., inability to walk, unstable joints, severe neurological impairment)
• Recently completed (i.e., <6 months), ongoing, or planned in- or outpatient EBR, or planned supervised outpatient physiotherapy for any indication
• Planned hospitalization during follow-up (e.g., elective surgery or inpatient chemotherapy)
• Contraindication to anticoagulation
• Life expectancy <1 year based on the treating physician's clinical judgement
• Known pregnancy
• Inability to speak German or French
• Participation in another study that prohibits concurrent participation in RehabPE
• Unable to provide informed consent (e.g., due to dementia)
• Unwilling to provide informed consent
• Prior enrollment in this study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

Switzerland · 6 centers

• Cantonal Hospital Aarau — Aarau
• Cantonal Hospital Baden — Baden
• Inselspital, Bern University Hospital — Bern
• Geneva University Hospitals — Geneva
• Lausanne University Hospital — Lausanne
• University Hospital Zürich — Zurich

Publications

• Luijten D, de Jong CMM, Ninaber MK, Spruit MA, Huisman MV, Klok FA. Post-Pulmonary Embolism Syndrome and Functional Outcomes after Acute Pulmonary Embolism. Semin Thromb Hemost. 2023 Nov;49(8):848-860. doi: 10.1055/s-0042-1749659. Epub 2022 Jul 12. PMID 35820428
• Keller K, Tesche C, Gerhold-Ay A, Nickels S, Klok FA, Rappold L, Hasenfuss G, Dellas C, Konstantinides SV, Lankeit M. Quality of life and functional limitations after pulmonary embolism and its prognostic relevance. J Thromb Haemost. 2019 Nov;17(11):1923-1934. doi: 10.1111/jth.14589. Epub 2019 Aug 13. PMID 31344319
• Sista AK, Klok FA. Late outcomes of pulmonary embolism: The post-PE syndrome. Thromb Res. 2018 Apr;164:157-162. doi: 10.1016/j.thromres.2017.06.017. Epub 2017 Jun 16. PMID 28641836
• Yu A, Ding W, Lin W, Cai J, Huang W. Application of pulmonary rehabilitation in patients with pulmonary embolism (Review). Exp Ther Med. 2022 Jan;23(1):96. doi: 10.3892/etm.2021.11019. Epub 2021 Dec 1. PMID 34976138
• Cires-Drouet RS, Mayorga-Carlin M, Toursavadkohi S, White R, Redding E, Durham F, Dondero K, Prior SJ, Sorkin JD, Lal BK. Safety of exercise therapy after acute pulmonary embolism. Phlebology. 2020 Dec;35(10):824-832. doi: 10.1177/0268355520946625. Epub 2020 Jul 27. PMID 32720853
• Amoury M, Noack F, Kleeberg K, Stoevesandt D, Lehnigk B, Bethge S, Heinze V, Schlitt A. Prognosis of patients with pulmonary embolism after rehabilitation. Vasc Health Risk Manag. 2018 Aug 30;14:183-187. doi: 10.2147/VHRM.S158815. eCollection 2018. PMID 30214219
• Gleditsch J, Jervan O, Haukeland-Parker S, Tavoly M, Geier O, Holst R, Klok FA, Johannessen HH, Ghanima W, Hopp E. Effects of pulmonary rehabilitation on cardiac magnetic resonance parameters in patients with persistent dyspnea following pulmonary embolism. Int J Cardiol Heart Vasc. 2022 Mar 23;40:100995. doi: 10.1016/j.ijcha.2022.100995. eCollection 2022 Jun. PMID 35345773
• Albaghdadi MS, Dudzinski DM, Giordano N, Kabrhel C, Ghoshhajra B, Jaff MR, Weinberg I, Baggish A. Cardiopulmonary Exercise Testing in Patients Following Massive and Submassive Pulmonary Embolism. J Am Heart Assoc. 2018 Mar 3;7(5):e006841. doi: 10.1161/JAHA.117.006841. PMID 29502109

Identifiers

NCT: NCT07143539 · 2025-01502

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗