Pulmonary Rehabilitation for Long COVID (Post COVID-19 Condition) (PuRe-COVID)

Changes in Functional Exercise Capacity After PUlmonary REhabilitation in Primary Care: a Randomized, Controlled, Multicenter, Pragmatic Trial in 134 Patients With Long COVID (PuRe-COVID)

In the PuRe COVID study (a randomized, controlled, multicenter, pragmatic trial) the investigators aim to assess the effect of a pulmonary rehabilitation program in primary care on exercise capacity (6MWT) and daily life physical activity in patients with long COVID.

134 patients with long COVID, defined by self-reported persistent COVID related symptoms ≥6 weeks after COVID-19 infection and a positive symptom score (CAT score ≥10 or mMRC score ≥2 or CIS-fatigue ≥36 or PCFS score of ≥2), will be recruited and divided into an intervention group or a control group. The intervention group will get twelve weeks of primary care pulmonary rehabilitation (PR) including coaching by primary care physiotherapists. The control group consists of usual care, which does not include a pulmonary rehabilitation program.

This study will help determine whether the type of symptoms or affected body system can impact recovery form long covid during rehabilitation and after follow-up. The investigators will analyze determinants and risk factors that characterize non-responders and non-adherers to better understand which patients with long COVID benefit from rehabilitation.

Study Overview

• Status: Completed
• Conditions: COVID-19; Long COVID; Post COVID-19 Condition
• Intervention / Treatment: Other: Pulmonary rehabilitation in primary care

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Antwerp
    • Edegem, Antwerp, Belgium, 2650
      • UHAntwerp
  • Limburg
    • Genk, Limburg, Belgium, 3600
      • Ziekenhuis Oost-Limburg

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult patients with status post COVID-19 (positive COVID-19 PCR or an official pharmacy performed antigen test or a self-performed test confirmed by a physician during the acute COVID-19 ≥ 6 weeks ago or positive antibodies before vaccination or positive antibodies before vaccination).
• Persistent COVID related symptoms that were not present pre-COVID-19 or were less severe pre-COVID.

• Symptomatic: quantified by dyspnea on exertion, loss of energy, fatigue or sleep impairment based upon the score of four questionnaires:

  • COPD Assessment Test (CAT) ≥10, and/or
  • modified Medical Research Council dyspnea scale (mMRC) ≥2, and/or
  • CIS-fatigue ≥36, and/or
  • post-COVID-19 Functional Status (PCFS) ≥2.

Exclusion Criteria:

• Patients with known or self-reported cognitive, hearing, visual, neurological or musculoskeletal conditions that make it impossible to participate in pulmonary rehabilitation.

• Prior physiotherapy for long COVID if:

  • patients who have completed ≥9 sessions of physiotherapy in total for long COVID.
  • patients who completed any physiotherapy session in the previous 12 weeks for long COVID (primary care or hospital based; pulmonary or non-pulmonary).
• Patients with predominantly neurological disorders impacting respiratory function will not be eligible for the study.
• Patients that are not able to give informed consent or not able to complete questionnaires.
• Patients who have had any organ transplatation in the past, have to undergo any transplantation or are on an active transplantation list.
• Patients with active malignancy and/or (maintenance) treatment for active malignancy or curatively treated carcinoma within the past year.

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
Active Comparator: Pulmonary rehabilitation group; The intervention group receives a 12 weeks pulmonary rehabilitation program supervised by a primary care physiotherapist consisting of maximum 36 sessions (3 sessions per week).	Other: Pulmonary rehabilitation in primary care; Pulmonary rehabilitation consists breathing exercises, exercise capacity, muscle strength and change towards an active lifestyle.
No Intervention: Control group without rehabilitation; The control group will receive usual care that doesn't include pulmonary rehabilitation or a supervised physical activity program.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exercise capacity	Change in functional exercise capacity measured by 6-minute walk test (6MWT).	Baseline - 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in physical activity	Change in physical activity as objectively measured by an activity tracker (number of steps).	Baseline - 12 weeks
Change in COVID-19 related symptoms	The COVID-19 related symptoms will be measured with the COPD assessment test (CAT). The total CAT score ranges from 0 to 40 where 0 represents no symptoms and 40 very bad symptoms.	Baseline - 12 weeks - 24 weeks - 36 weeks
Change in fatigue	The changes of the level of fatigue will be measured with the Checklist Individual Strength -fatigue (CIS-fatigue) score. The total CIS-fatigue score ranges from 20 to 140 where 20 represents no symptoms and 140 very bad symptoms.	Baseline - 12 weeks - 24 weeks - 36 weeks
Change in functional status	The functional status will be measured by the post COVID-19 functional status scale (PCFS). It is an ordinal score ranging from 0 to 4 where 4 means the patient has a lot of limitations in daily life.	Baseline - 12 weeks - 24 weeks - 36 weeks
Change in exercise capacity	The functional exercise capacity will be measured by 6-minute walk test (6MWT).	Baseline - 24 weeks
Change in quality of life	The quality of life will be measured with the EQ-5D-5L.	Baseline - 12 weeks - 24 weeks - 36 weeks
Change in dyspnoea	Changes in dyspnoea, measured with the modified medical research council (mMRC). The total mMRC scale ranges from 0 to 4 score where 0 represents no dyspnoea and 4 a lot of dyspnoea.	Baseline - 24 weeks - 36 weeks
Change in work productivity and activity impairment.	This will be measured with the "work productivity and activity impairment" questionnaire (WPAI), consisting of 6 questions.	Baseline - 24 weeks - 36 weeks
Change in anxiety and depression symptoms.	This will be measured by the Hospital Anxiety and depression scale (HADS). The HADS is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. The anxiety and depression subscales each range from 0 to 21, with higher scores indicating higher anxiety/depression complains. Patients were defined as having anxiety or depression or both if the score was 8 or more in the corresponding subscale.	Baseline - 24 weeks - 36 weeks
Change in dysfunctional breathing	This will be measured with the Nijmegen questionnaire. 16 questions will be asked, ranging from 0 to 4. The higher the score, the more likely it is that they have dysfunctional breathing.	Baseline - 24 weeks - 36 weeks
Predictors of response in 6- minute walk distance (6MWD)	The predictors will be based on baseline symptom scores (CAT, mMRC, CIS), baseline 6MWD and hospitalisation status.	Post pulmonary rehabilitation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The cost-effectiveness of the intervention.	In case the study findings on the primary outcome is positive, a cost-effectiveness analysis will be done to evaluate if the intervention had an impact on the health care costs verified through the financial expenses of patients.	Baseline - end of the study
Evaluate the change in 6MWD after 6weeks or 12weeks PR.	The investigators will evaluate the 6MWD at 6 weeks and 12 weeks, as well as change in 6MWD from baseline to 6 weeks versus from baseline to 12 weeks PR.	Baseline - 6 weeks / 12 weeks
Change in hand grip strength.	This change will be objectived by measuring the hand grip strength with the Jamar hand-held dynamometer.	Baseline - 12 weeks
Change in respiratory muscle and diaphragm strength.	This change will be objectived by measuring the maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP).	Baseline - 12 weeks
Change in dyspnoea	Changes in dyspnoea, measured with the modified medical research council (mMRC). The total mMRC scale ranges from 0 to 4 score where 0 represents no dyspnoea and 4 a lot of dyspnoea.	Baseline - 12 weeks
Change in sleep efficiency.	The change in sleep efficiency will be measured by an activity tracker.	Baseline - 12 weeks
Change in functional status	The functional status will be measured by the post COVID-19 functional status scale (PCFS). It is an ordinal score ranging from 0 to 4 where 4 means the patient has a lot of limitations in daily life.	Baseline - 12 weeks
Change in anxiety and depression symptoms.	This will be measured by the Hospital Anxiety and depression scale (HADS). The HADS is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. The anxiety and depression subscales each range from 0 to 21, with higher scores indicating higher anxiety/depression complains. Patients were defined as having anxiety or depression or both if the score was 8 or more in the corresponding subscale.	Baseline - 12 weeks
Change in work productivity and activity impairment.	This will be measured with the "work productivity and activity impairment" questionnaire (WPAI), consisting of 6 questions.	Baseline - 12 weeks
Change in dysfunctional breathing	This will be measured with the Nijmegen questionnaire. 16 questions will be asked, ranging from 0 to 4. The higher the score, the more likely it is that they have dysfunctional breathing.	Baseline - 12 weeks

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp
• Collaborators: Hasselt University; Ziekenhuis Oost-Limburg; Universiteit Antwerpen
• Investigators: Principal Investigator: Thérèse Lapperre, Prof., University Hospital, Antwerp

Publications and helpful links

Helpful Links

• Published PuRe-COVID protocol

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2022
• Primary Completion (Actual): December 18, 2023
• Study Completion (Actual): February 29, 2024

Study Registration Dates

• First Submitted: February 14, 2022
• First Submitted That Met QC Criteria: February 16, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): October 1, 2024
• Last Update Submitted That Met QC Criteria: September 27, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Pulmonary rehabilitation; Physiotherapy; Respiratory physiotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Chronic Disease; Post-Infectious Disorders; COVID-19; Disease; Post-Acute COVID-19 Syndrome
• Other Study ID Numbers: UZA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial, after deidentification.
• IPD Sharing Time Frame: Data requests can be submitted starting after the publication of the primary endpoint and either publication of the follow-up data article or one year after the clinical study report is provided to the funder, whichever happens earlier. The data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• IPD Sharing Access Criteria: Access to anonymized trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) by the TSC and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact purecovid@uza.be . An administrative cost may apply.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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