Symptom-based Rehabilitation Compared to Usual Care in Post-COVID - a Randomized Controlled Trial (RELOAD)

Inpatient, multimodal rehabilitation represents one of the most important interventions in the disease management of post/long COVID. Different professional societies, including the German Society of Pneumology and the European Respiratory Society, recommend rehabilitation intervention to reduce the sequelae of COVID-19. However, from the perspective of science and practice, there are relevant areas that have been insufficiently investigated and are essential for the treatment success of post/long COVID patients:

• Differentiation of rehabilitation effects from natural recovery after COVID-19.
• Lack of personalized and symptom-based treatment approaches that can address the heterogeneity of symptoms in post/long COVID
• Lack of uniform, high-quality rehabilitation standards in post-/long-COVID.

Therefore, post-COVID patients will be recruited at several post-COVID practices around Germany and randomized to receive (A) a rehabilitation program or (B) usual care. The primary objective of this randomized controlled trial (RCT) is to investigate whether a 3-week symptom-oriented, inpatient, multidisciplinary rehabilitation intervention, whose content focus is standardized according to cluster assignment (fatigue, cognition, soma), has a positive effect on the quality of life (primary outcome) in post-COVID syndrome patients compared to a usual care group (standard outpatient care). All study participants will be provided with a continuous telemonitoring system (SaniQ app) throughout the study period. After the interventional phase, there will be a 3 months follow-up assessment to evaluate the maintenance effects of COVID rehabilitation.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19; Long-COVID
• Intervention / Treatment: Other: symptom-focused rehabilitation; Other: usual care

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rainer Gloeckl, PhD; Phone Number: +49-8652-931630; Email: rgloeckl@schoen-klinik.de

Study Locations

• Germany
  • Augsburg, Germany
    • University Hospital Augsburg
  • Bad Reichenhall, Germany
    • Praxis Dr. Schrag
  • Berlin, Germany
    • Pneumologen Lichterfelde Berlin
  • Erlangen, Germany
    • Praxis im Zentrum Erlangen
  • Marburg, Germany
    • Pneumopraxis Marburg
  • Munich, Germany
    • Lungenärzte am Rundfunkplatz, München
  • Schwabach, Germany
    • Praxis Dr. Roch
  • Schönau am Königssee, Germany
    • COVID ambulance Prof. Koczulla

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Post-COVID Syndrome according to World Health Organisation definition (persistent symptoms for at least 3 months after PCR-test confirmed SARS-CoV 2 infection)

Exclusion Criteria:

• no walking ability
• not able to operate smartphone apps
• rehabilitation program within the previous 6 months

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: Symptom-focused Rehabilitation; Patients in this arm will be referred to a 3-week inpatient comprehensive rehabilitation program. Initially, patients will be classified into one out of three clusters namely: Cluster A (Fatigue), Cluster B (cognition), or Cluster C (physical). The content of the rehabilitation program will be individually adapted according to the patient's most relevant symptom cluster.	Other: symptom-focused rehabilitation; Patients in this arm will be referred to a 3-week inpatient comprehensive rehabilitation program. Initially, patients will be classified into one out of three clusters namely: Cluster A (Fatigue), Cluster B (cognition), or Cluster C (physical). The content of the rehabilitation program will be individually adapted according to the patient's most relevant symptom cluster.
Other: Usual Care; Patients in this arm do not receive any intervention beyond usual care during the study phase. However, all patients in this group will get the opportunity to also receive a rehabilitation program after the study phase.	Other: usual care; Patients in this arm do not receive any intervention beyond usual care during the study phase. However, all patients in this group will get the opportunity to also receive a rehabilitation program after the study phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline Quality of life assessed by Short Form - 12 Questionnaire at week 4 and week 12	the scale of the physical and mental Health component summary score ranges from minimum 0 to maximum 100 points with higher scores indicating better quality of life	baseline, week 4, week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline COVID-related symptoms at week 4 and week 12	the number of COVID-symptoms will recorded as well as their intensity will be rated on a scale from 0 [not relevant] until 10 [very severe symptom].	baseline, week 4, week 12
Change from baseline lung function at week 4 and week 12	following Parameters will be collected: forced expiratory volume in 1 sec, peak flow, forced vital capacity, total lung capacity, diffusion lung capacity for carbonmonoxide	baseline, week 4, week 12
Change from baseline blood gas analysis at week 4 and week 12	following parameters will be collected at rest and at the end of an incremental cycle test: partial pressure for oxygen and carbon dioxide	baseline, week 4, week 12
Change from baseline Cardiac Doppler echocardiography at week 4 and week 12	Left and right heart echocardiography will be performed	baseline, week 4, week 12
Change from baseline laboratory parameters at week 4 and week 12	blood samples will be taken from venous blood	baseline, week 4, week 12
Change from baseline exercise performance at week 4 and week 12	incremental cardiopulmonary exercise testing will be performed with spirometry	baseline, week 4, week 12
Change from baseline health care service needs at week 4 and week 12	Number of visits at the general practitioner, pulmonologist, psychologist, physiotherapist, COVID-ambulance, hospital admission until the last visit will be recorded	baseline, week 4, week 12
Change from baseline working capability at week 4 and week 12	number of days of incapacity to work until the last visit will be recorded	baseline, week 4, week 12
Change from baseline sleep quality at week 4 and week 12	Sleep quality will be assessed by using the Pittsburgh Sleep Quality Index (total score ranges from 0 to 21 with higher scores indicating higher impairment)	baseline, week 4, week 12
Change from baseline sleep quality at week 4 and week 12	daytime sleepiness will be assessed by using the Epworth Sleepiness Scale (total score ranges from 0 to 24 with higher scores indicating higher impairment)	baseline, week 4, week 12
Change from baseline Depression status assessed by Patient Health Questionnaire 9	the total score ranges from 0 to 27 points with higher scores indicating worse Depression symptoms	baseline, week 4, week 12
Change from baseline Depression status assessed by Generalized Anxiety Disorder Scale 7	the total score ranges from 0 to 21 points with higher scores indicating more anxiety symptoms	baseline, week 4, week 12
Change from baseline resilience assessed by resilience scale 13	the total score ranges from 13 to 91 points with higher scores indicating higher resilience	baseline, week 4, week 12
Change from baseline cognitive status assessed by Montreal Cognitive Assessment Test	the total score ranges from 0 to 30 points with higher scores indicating a better cognitive status	baseline, week 4, week 12
Change from baseline dyspnea assessed by Modified Medical Research Counsil score at week 4 and week 12	the total score ranges from 0 to 4 points with higher scores indicating more dyspnea	baseline, week 4, week 12
Change from baseline dysfunctional breathing assessed by Nijmegen breathing questionnaire at week 4 and week 12	the total score ranges from 0 to 64 points with higher scores indicating hyperventilation	baseline, week 4, week 12
Change from baseline chronic fatigue syndrome assessed by fatigue assessment scale at week 4 and week 12	the total score ranges from 10 to 50 points with higher scores indicating more fatigue	baseline, week 4, week 12
Change from baseline chronic fatigue syndrome assessed by canadian consensus criteria at week 12	the canadian consensus criteria indicate if patients developed a chronic fatigue syndrome/myalgic encephalomyelitis	baseline, week 12
Change from baseline functional status assessed by post-COVID functional status scale at week 4 and week 12	the total score ranges from 0 to 4 points with higher scores indicating more impairment	baseline, week 4, week 12
Change from baseline physical activity assessed by Garmin watch at week 4 and week 12	daily total steps per day will be recorded by a Garmin watch linked to the SaniQ App	baseline, week 4, week 12
Change from baseline blood pressure assessed at week 4 and week 12	blood pressure will be measured at the upper arm using the Aponorm device	baseline, week 4, week 12
Change from baseline oxygen saturation assessed by pulse oximeter at week 4 and week 12	Beurer pulse oximeter	baseline, week 4, week 12
Change from baseline peak flow assessed by peak flow meter at week 4 and week 12	peak flow will be assessed by smart one spirometer	baseline, week 4, week 12

Collaborators and Investigators

• Sponsor: Schön Klinik Berchtesgadener Land
• Collaborators: Bavarian State Office for Health and Food Safety; Praxis im Zentrum Erlangen; Pneumologen Lichterfelde Berlin; Pneumopraxis Marburg; COVID ambulance Philipps-University Marburg; Pneumologie Elisenhof Munich; COVID ambulance Pneumology LMU Munich; COVID ambulance psychology LMU Munich; University Clinic Augsburg; COVID ambulance Schön Klinik Schönau

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2022
• Primary Completion (Estimated): November 30, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: December 22, 2021
• First Submitted That Met QC Criteria: December 23, 2021
• First Posted (Actual): December 29, 2021

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: rehabilitation; quality of life; recovery; intervention; long-COVID; post-COVID syndrome; sequelae
• 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; Post-Acute COVID-19 Syndrome
• Other Study ID Numbers: RELOAD

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