Trial Report Improved functional exercise capacity after primary care pulmonary rehabilitation in patients with long COVID (PuRe-COVID): [RCT], 2025, Volckaerts+

[Andy]

Protocol
See next post for the Trial Report


Full title: Randomised, controlled, open-label pragmatic trial evaluating changes in functional exercise capacity after primary care PUlmonary REhabilitation in patients with long COVID: protocol of the PuRe-COVID trial in Belgium

Introduction

Long COVID is a prevalent condition with many multisystemic symptoms, such as fatigue, dyspnoea, muscle weakness, anxiety, depression and sleep difficulties, impacting daily life and (social and physical) functioning. Pulmonary rehabilitation (PR) may improve physical status and symptoms of patients with long COVID, yet the evidence is limited. Therefore, this trial aims to study the effect of primary care PR on exercise capacity, symptoms, physical activity and sleep in patients with long COVID.

Methods and analysis

PuRe-COVID is a prospective, pragmatic, open-label, randomised controlled trial. A sample of 134 adult patients with long COVID will be randomised to a 12 week PR programme in primary care, supervised by a physiotherapist or to a control group, following no PR. A 3 month and 6 month follow-up period is foreseen. The primary endpoint will be the change in exercise capacity measured by 6-minute walk distance (6MWD) at 12 weeks, hypothesising a more significant improvement in the PR group. Other parameters, such as pulmonary function tests (including maximal inspiratory pressure/maximal expiratory pressure), patient-reported outcomes (COPD Assessment Test, modified Medical Research Council Dyspnoea Scale, Checklist Individual Strength, post-COVID-19 Functional Status, Nijmegen questionnaire, Hospital Anxiety and Depression Scale, Work Productivity and Activity Impairment Questionnaire and EuroQol-5D-5L), physical activity measured by an activity tracker, hand grip strength and sleep efficiency, are secondary and exploratory outcomes.

The recruitment started on 19 April 2022, and 52 patients were included as of 14 December 2022.

Ethics and dissemination

Ethical approval was obtained in Belgium from the relevant institutional review boards on 21 February 2022 (Antwerp University Hospital, approval number 2022-3067) and on 1 April 2022 (Ziekenhuis Oost-Limburg in Genk, approval number Z-2022-01). Findings from this randomised controlled trial will be disseminated in peer-reviewed publications and presentations at international scientific meetings.

Trial registration number NCT05244044.

Open access, https://bmjopen.bmj.com/content/13/6/e071098

 

[forestglip]

Improved functional exercise capacity after primary care pulmonary rehabilitation in patients with long COVID (PuRe-COVID): a pragmatic randomised controlled trial

Spoiler: Authors

Volckaerts, Tess; Ruttens, David; Quadflieg, Kirsten; Burtin, Chris; Cops, Dries; De Soomer, Kevin; Roelant, Ella; Verhaegen, Iris; Daenen, Marc; Criel, Maarten; Vissers, Dirk; Lapperre, Therese

Background
Pulmonary rehabilitation (PR) improves physical status and symptoms in patients with long COVID, but access to specialised hospital-based centres is challenging. This trial studied the effect of primary care PR on functional exercise capacity and symptoms in patients with long COVID.

Methods
In this pragmatic randomised controlled trial (PuRe-COVID), patients with long COVID were randomised to a 12-week stepwise PR programme in primary care, or to a control group without PR. The primary end point was change in 6 min walk distance (6MWD) from baseline to 12 weeks. Additional outcomes, measured at 6, 12, 24 and 36 weeks, included patient-reported outcomes, physical activity, maximal inspiratory (MIP) and expiratory pressures and hand grip strength.

Results
In total, 76 patients were randomised (PR/control group (n=39/37); mean age 49±13 years).

The change in 6MWD at 12 weeks was estimated to be +39 m in the PR group compared with the control group (95% CI (18 to 59), p<0.001). Furthermore, a decrease in Checklist Individual Strength (CIS)-fatigue was found for the PR group (−6 points; 95% CI (−10 to –2), p=0.011).

At 12 weeks, patients in the intervention group were more likely to have a clinically significant improvement in 6MWD (OR 5.7, 95% CI (2.0 to 16.1), p=0.001), CIS-fatigue (OR 3.8, 95% CI (1.2 to 12.0), p=0.020), MIP (OR 3.7, 95% CI (1.05 to 12.7), p=0.036) and modified Medical Research Council dyspnoea score (OR 5.2, 95% CI (1.6 to 16.4), p=0.003).

Conclusions
Primary care stepwise individual PR may improve functional exercise capacity, fatigue and dyspnoea in patients with long COVID. It therefore may be a promising treatment option in primary care for patients with long COVID experiencing fatigue and/or respiratory symptoms. Trial registration number NCT05244044 .

Web | DOI | BMJ Open Respiratory Research

 

[Utsikt]

Only 76 out of 381 were recruited. Their target was 134, almost double.

Baseline characteristics are presented in table 1 for the intention-to-treat population (n=76). Patients had borderline normal 6MWD values (intervention group: 83.4±11.9% predicted, control group: 83.2±14.6% predicted).

They had almost normal 6MWT results at baseline, which brings into question how appropriate the measurement is as a primary outcome, and how physically impaired the patients actually were.

Figure 2

Mean 6MWD, CIS-fatigue, MIP and mMRC dyspnoea scale values over time with 95% CI per time point per group. P values from post hoc contrasts of change from baseline at each time point between groups, estimated with the linear mixed model (corrected for multiple testing using Bonferroni-Holm correction). 6MWD, 6 min walk distance; CIS, Checklist Individual Strength; MIP, maximal inspiratory pressure; mMRC: modified Medical Research Council. ·P<0.1, *p<0.05, **p<0.01 and ***p<0.001.

There is some discussion about the limitations of this study and especially the generalisability of the findings, but as is tradition, the authors still go on to make a generalised conclusion:

this PR programme in primary care, consisting of five phases, is a safe and effective intervention that may improve functional exercise capacity, fatigue and dyspnoea in patients with long COVID.

 

[Hutan]

They had almost normal 6MWT results at baseline, which brings into question how appropriate the measurement is as a primary outcome, and how physically impaired the patients actually were.

I've posted about the 6MWT not being a good outcome and not being very objective - see here:
Six minute walking test

I personally don't think the six minute walking test is a good objective measure for people with mild ME/CFS, the people who are likely to choose to participate in a study like this. Unless a person slides down to a lower level of severity where walking becomes difficult, I don't think a person with mild ME/CFS on a good day is hindered when walking for 6 minutes. It therefore becomes more of a subjective outcome - how determined are you to walk fast and keep up that pace? If you come to like your instructors and want to help the research, you will probably try harder at the end of the trial than at the beginning.

 

[Trish]

I think one of the biggest problems with the 6 minute walk test is the lack of any follow up in the days after it. No information on whether and how badly they triggered PEM.