RECOVER-ENERGIZE Platform Protocol

NCT ID: NCT06404047

Last Updated: 2025-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

660 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-17

Study Completion Date

2025-10-30

Brief Summary

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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

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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.

Conditions

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Long COVID Long Covid19 Long Covid-19

Keywords

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PASC Exercise PEM (post exertional malaise)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This platform protocol is designed to allocate participants into an appropriate intervention appendix based on their symptoms of exercise intolerance or post-exertional malaise (PEM). Once assigned to an appendix, eligible participants are randomized in a 1:1 ratio to either the study intervention group or a control group.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Appendix A: Single (Outcomes Assessor masked) The assessor of the primary outcome, Endurance Shuttle Walk Test (ESWT), is blinded.

Appendix B: None (open label / no masking)

Study Groups

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Experimental: Appendix A - Cardiopulmonary Rehabilitation (Exercise Intolerance)

Appendix A is a randomized controlled trial designed to evaluate the effect of a 12-week personalized cardiopulmonary rehabilitation intervention on exercise tolerance in participants with PASC.

Participants who meet eligibility criteria for Appendix A will be assigned to either Personalized Cardiopulmonary Rehabilitation (study intervention group) or Education (control group) in a 1:1 ratio. The intervention duration is 12 weeks with a follow-up period of 3 months (total study duration of 6 months).

Anticipated enrollment is 360 participants. Details about Appendix A: Cardiopulmonary Rehabilitation (Exercise Intolerance) are available under NCT06404060.

Group Type EXPERIMENTAL

Personalized Cardiopulmonary Rehabilitation

Intervention Type BEHAVIORAL

Participants in this group will complete 2-3 cardiopulmonary rehabilitation sessions per week, for 12 weeks, as tolerated. Rehabilitation sessions are provided by respiratory therapists, exercise physiologists, physical therapists, nurses, or others who have experience and training in either pulmonary or cardiac rehabilitation.

Rehabilitation sessions (adjusted based on the participant's baseline assessment, symptoms, and progress) last about 1 hour and include education, aerobic exercise, strength, and flexibility training.

Education

Intervention Type OTHER

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.

Experimental: Appendix B - Structured Pacing (PEM)

Appendix B is a randomized controlled trial designed to evaluate the effect of a 12-week Structured Pacing intervention on reducing the symptoms of post-exertional malaise (PEM) in participants with PASC.

Participants who meet eligibility criteria for Appendix B will be assigned to either Structured Pacing (study intervention group) or Usual Care (control group) in a 1:1 ratio. The intervention duration is 12 weeks with a follow-up period of 3 months (total study duration of 6 months).

Anticipated enrollment is 300 participants. Details about Appendix B: Structured Pacing (PEM) are available under NCT06404073.

Group Type EXPERIMENTAL

Structured Pacing

Intervention Type BEHAVIORAL

Participants in this group will complete weekly pacing sessions for 12 weeks. Pacing sessions will last about 30 minutes, as tolerated. Each participant will meet with a provider 'pacing coach' who has received study-specific education about PEM and how to create and manage pacing strategies for participants. Sessions include PEM symptom and trigger assessment; task, function and activity analysis; adaptations and modifications.

Usual Care

Intervention Type OTHER

Participants in this group will receive basic education about PEM with a weekly call by site study staff for support and communication.

Interventions

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Personalized Cardiopulmonary Rehabilitation

Participants in this group will complete 2-3 cardiopulmonary rehabilitation sessions per week, for 12 weeks, as tolerated. Rehabilitation sessions are provided by respiratory therapists, exercise physiologists, physical therapists, nurses, or others who have experience and training in either pulmonary or cardiac rehabilitation.

Rehabilitation sessions (adjusted based on the participant's baseline assessment, symptoms, and progress) last about 1 hour and include education, aerobic exercise, strength, and flexibility training.

Intervention Type BEHAVIORAL

Structured Pacing

Participants in this group will complete weekly pacing sessions for 12 weeks. Pacing sessions will last about 30 minutes, as tolerated. Each participant will meet with a provider 'pacing coach' who has received study-specific education about PEM and how to create and manage pacing strategies for participants. Sessions include PEM symptom and trigger assessment; task, function and activity analysis; adaptations and modifications.

Intervention Type BEHAVIORAL

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.

Intervention Type OTHER

Usual Care

Participants in this group will receive basic education about PEM with a weekly call by site study staff for support and communication.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. ≥ 18 years of age at the time of enrollment
2. Previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization\*

* Suspected\* or probable SARS-CoV-2 infection will only be allowed if it occurred before May 1, 2021, and will be limited to no more than 10% of the study population. Otherwise, confirmed cases are required.

Suspected case of SARS-CoV-2 infection - Three options, A through C:

A. A person who meets the clinical OR epidemiological criteria. Clinical criteria: Acute onset of fever AND cough (influenza-like illness) OR Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, nausea, diarrhea, anorexia. Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster; or B. Acute respiratory infection with history of fever or measured fever of ≥ 38°C; and cough; with onset within the last 10 days; and who requires hospitalization; or C. With no clinical signs or symptoms, NOR meeting epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.

Probable case of SARS-CoV-2 infection:

A. A patient who meets clinical criteria above AND is a contact of a probable or confirmed case or is linked to a COVID-19 cluster.

Confirmed case of SARS-CoV-2 infection - Two options, A and B:

A. A person with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or B. Meeting clinical criteria AND/OR epidemiological criteria (See suspected case A above for criteria). With a positive professional use or self-test SARS- CoV-2 Antigen-Rapid Diagnostic Test.
3. Self-reported limitation to physical activity due to the presence of symptoms such as fatigue, shortness of breath, and/or PEM following a SARS-CoV-2 infection, that has persisted for at least 12 weeks and is present at the time of consent.
4. Willing, able, and agree to provide informed consent, complete questionnaires and outcome assessments, and participate in the study, including assigned intervention or control and study visits whether remote, hybrid, or in-person.

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Known active acute SARS-CoV-2 infection ≤ 4 weeks prior to the consent.
2. Known prior diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), not related to SARS-CoV-2 infection.
3. Current or recent use (within the last 14 days) of a formal program utilizing one or more of the current study intervention(s) or similar intervention(s) to treat the underlying condition, unless a washout period is permitted per Appendices.
4. Participation in another interventional clinical trial.
5. Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gary M Felker, MD

Role: STUDY_CHAIR

Duke Clinical Research Institute

Barry Make, MD

Role: STUDY_CHAIR

National Jewish Health

Lucinda Bateman, MD

Role: STUDY_CHAIR

Bateman Horne Center

Janna Friedly, MD, MPH

Role: STUDY_CHAIR

University of Washington

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Banner University Medical Center Phoenix

Phoenix, Arizona, United States

Site Status

Banner University Medical Center Tucson

Tucson, Arizona, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Torrance, California, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

Yale - New Haven Hospital

New Haven, Connecticut, United States

Site Status

University of Florida College of Medicine Jacksonville

Jacksonville, Florida, United States

Site Status

Innovation Clinical Trials Inc.

Miami, Florida, United States

Site Status

Valencia Medical and Research Center

Miami, Florida, United States

Site Status

Grady Memorial Hospital (Emory)

Atlanta, Georgia, United States

Site Status

Emory Hope Clinic

Decatur, Georgia, United States

Site Status

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

North Shore University HealthSystem/Evanston Hospital

Evanston, Illinois, United States

Site Status

Saint Francis Medical Center

Peoria, Illinois, United States

Site Status

Cedar Valley Clinical Research

Waterloo, Iowa, United States

Site Status

Kansas University Medical Center

Kansas City, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Maine Health Institute of Research

Scarborough, Maine, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Med. Ctr.

Boston, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, United States

Site Status

NYU Langone Health/Brooklyn Hospital

Brooklyn, New York, United States

Site Status

University of North Carolina Hospital

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Avera McKennan Hospital & University Health Center

Sioux Falls, South Dakota, United States

Site Status

Southwest Family Medicine Associates

Dallas, Texas, United States

Site Status

Houston Methodist Hospital

Houston, Texas, United States

Site Status

University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Vermont Lung Center, University of Vermont

Colchester, Vermont, United States

Site Status

University Physicians and Surgeons, Inc dba Marshall Health

Huntington, West Virginia, United States

Site Status

West Virginia Clinical and Translational Science Institute

Morgantown, West Virginia, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Informed Consent Form

View Document

Related Links

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Other Identifiers

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OT2HL156812

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NHLBI Grant to RTI

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Pro00112409

Identifier Type: -

Identifier Source: org_study_id