RECOVER-ENERGIZE Platform Protocol_Appendix A (Exercise Intolerance)

Not Applicable

Recruiting

• Conditions: Long COVID; Long Covid19; Long Covid-19
• Interventions: Behavioral: Personalized Cardiopulmonary Rehabilitation; Other: Education

• Registration Number: NCT06404060
• Lead Sponsor: Duke University

Brief Summary

This is a platform protocol designed to be flexible so that it is suitable for a range of interventions and settings within diverse health care systems and community settings with incorporation into clinical COVID-19 management programs and treatment plans if results achieve key study outcomes.

This protocol is a prospective, multi-center, multi-arm, randomized, controlled platform trial evaluating interventions to address and improve exercise intolerance and post-exertional malaise (PEM) as manifestations of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC).

The focus of this protocol is to assess interventions that can improve exercise capacity, daily activities tolerance, and quality of life in patients with PASC.

Detailed Description

Study interventions will be added to the platform protocol as appendices. Each appendix will leverage all elements of the platform protocol, with additional elements described in the individual appendix. Study intervention appendices may be added or removed according to adaptive design and/or emerging evidence.

The platform protocol enrolls participants who meet study eligibility criteria. After completing initial screening assessments, eligible participants are assigned to one of the study intervention appendices that are actively enrolling. Participants must meet certain criteria within a specific appendix in order to be included in that appendix. Once assigned to an appendix, eligible participants are randomized to either the study intervention group or a control group.

Study Timeline

• Study First Submitted: 2024-05-03
• Study First Submitted QC: 2024-05-06
• Study First Posted: 2024-05-08
• Status Verified: 2024-06
• Study Start: 2024-07-17
• Last Update Submitted: 2025-05-19
• Last Update Posted: 2025-05-20
• Primary Completion: 2026-07
• Study Completion: 2026-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 360

Inclusion Criteria

• See NCT06404047 for RECOVER-ENERGIZE: Platform Protocol level inclusion and exclusion criteria which applies to this appendix

Additional Appendix A (Cardiopulmonary Rehabilitation (Exercise Intolerance)) Level

Exclusion Criteria

1. Known pre-existing postural orthostatic tachycardia syndrome, not related to SARS-CoV-2 infection
2. Known uncontrolled hypertension (blood pressure [BP] ≥ 160/100 mmHg at rest)
3. Any of the following within 4 weeks of enrollment - acute myocardial infarction, unstable angina, uncontrolled arrhythmias causing symptoms or hemodynamic compromise, acute myocarditis or pericarditis, uncontrolled acutely decompensated heart failure (acute pulmonary edema), acute pulmonary embolism, suspected dissecting aneurysm, severe hypoxemia at rest, thromboembolic event(s), any acute or chronic disorder that may affect exercise capacity or be aggravated by exercise (e.g., infection, exercise induced syncope, thyrotoxicosis, unable to cooperate)
4. Score of 2 or greater for both frequency and severity for any of the first 5 questions on the Screening mDSQ-PEM AND answer of 'YES' to either item 7 or 8 on the Screening mDSQ-PEM, and response of > 14 hours in item 9 OR Score of 3 or greater on any severity question (regardless of frequency) AND answer of 'YES' to either item 7 or 8 on the Screening mDSQ-PEM, and response of > 14 hours in item 9 OR Any score of 3 or greater on any of the severity questions on the mDSQ-PEM 48-72 hours following the Screening ISWT test
5. A selection of ≥ 8 on question 1 or ≥ 9 on question 3 of the OH Activity Scale from the mOHQ
6. Engaged in purposeful moderate or greater intensity exercise with the intent to improve one's health 2 or more times per week over the 30 days prior to informed consent
7. Inability to walk

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cardiopulmonary Rehabilitation (Exercise Intolerance)	Personalized Cardiopulmonary Rehabilitation	Participants assigned to Cardiopulmonary Rehabilitation will undergo a 12-week personalized cardiopulmonary rehabilitation intervention with a follow-up period of 3 months (total study duration of 6 months).
Education	Education	Participants in this group will receive two general education sessions at the start of the intervention with weekly phone/virtual follow-ups from site study staff.

Primary Outcome Measures

Name	Time	Method
Change in Endurance Shuttle Walk Test (ESWT)	Baseline, week 12 (End of Intervention (EOI))	The ESWT consists of timed walking on a 10m course. The result is expressed as total walking time after an initial 2-minute warm-up. The ESWT is an outcome measure of exercise capacity.
Percentage of participants meeting pre-specified change (minimal important difference) from baseline to End of Intervention on the ESWT	Week 12 (EOI)	The ESWT consists of timed walking on a 10m course. The result is expressed as total walking time after an initial 2-minute warm-up. The ESWT is an outcome measure of exercise capacity.

Secondary Outcome Measures

Name	Time	Method
Change in physical function, as measured by actigraphy	Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)
Change in symptom severity, as measured by the Modified DePaul Symptom Questionnaire - Post-Exertional Malaise (mDSQ-PEM)	Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)	Symptom severity is rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe.
Change in symptom duration, as measured by the Modified DePaul Symptom Questionnaire - Post-Exertional Malaise (mDSQ-PEM)	Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)
Change in physical function, as measured by the PROMIS SF-Physical Function (PROMIS-PF)	Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)	The PROMIS Short Form v2.0 - Physical Function 8b (PROMIS-PF) consists of 8 items. The PROMIS Physical Function instruments measure self-reported capability rather than actual performance of physical activities.
Change in symptom frequency, as measured by the Modified DePaul Symptom Questionnaire - Post-Exertional Malaise (mDSQ-PEM)	Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)	Symptom frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time.

Trial Locations

Locations (1)

All sites listed under NCT06404047; 🇺🇸 Durham, North Carolina, United States