RECOVER-ENERGIZE Platform Protocol

NCT06404047 | Completed DMC

• 3 other identifiers: Pro00112409OT2HL156812NHLBI Grant to RTI
• Study Type: interventional
• Target: 660
• Locations: 1 country
• Sites: 42

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.

Conditions

Long COVID; Long Covid-19

Keywords

PASC; Exercise; PEM (post exertional malaise)

Outcome Measures

Primary Outcomes (1)

• Total number of participants enrolled in each Appendix

  Total number of participants enrolled in each Appendix will be reported. Appendix-specific outcome measure data will be reported under the associated NCT#

  6 months

Study Arms (2)

Experimental: Appendix A - Cardiopulmonary Rehabilitation (Exercise Intolerance)

EXPERIMENTAL

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.

Behavioral: Personalized Cardiopulmonary Rehabilitation; Other: Education

Experimental: Appendix B - Structured Pacing (PEM)

EXPERIMENTAL

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.

Behavioral: Structured Pacing; Other: Usual Care

Interventions

Personalized Cardiopulmonary Rehabilitation 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.

Experimental: Appendix A - Cardiopulmonary Rehabilitation (Exercise Intolerance)

Structured Pacing 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.

Experimental: Appendix B - Structured Pacing (PEM)

Education 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 A - Cardiopulmonary Rehabilitation (Exercise Intolerance)

Usual Care OTHER

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

Experimental: Appendix B - Structured Pacing (PEM)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age at the time of enrollment
• 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.
• 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.
• 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.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Known active acute SARS-CoV-2 infection ≤ 4 weeks prior to the consent.
• Known prior diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), not related to SARS-CoV-2 infection.
• 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.
• Participation in another interventional clinical trial.
• Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study.

Sponsors & Collaborators

• Duke University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (42)

University of Alabama at Birmingham

Birmingham, Alabama, 35205, United States

Location

Banner University Medical Center Phoenix

Phoenix, Arizona, 85006, United States

Location

Banner University Medical Center Tucson

Tucson, Arizona, 85719, United States

Location

Stanford University

Stanford, California, 94035, United States

Location

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Torrance, California, 90509, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Yale - New Haven Hospital

New Haven, Connecticut, 06520-8017, United States

Location

University of Florida College of Medicine Jacksonville

Jacksonville, Florida, 32209, United States

Location

Innovation Clinical Trials Inc.

Miami, Florida, 33144, United States

Location

Valencia Medical and Research Center

Miami, Florida, 33165, United States

Location

Grady Memorial Hospital (Emory)

Atlanta, Georgia, 30303, United States

Location

Emory Hope Clinic

Decatur, Georgia, 30030, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60608, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

North Shore University HealthSystem/Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Saint Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Cedar Valley Clinical Research

Waterloo, Iowa, 50701, United States

Location

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Maine Health Institute of Research

Scarborough, Maine, 04074, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Med. Ctr.

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, 87102, United States

Location

NYU Langone Health/Brooklyn Hospital

Brooklyn, New York, 11220, United States

Location

University of North Carolina Hospital

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Avera McKennan Hospital & University Health Center

Sioux Falls, South Dakota, 57108, United States

Location

Southwest Family Medicine Associates

Dallas, Texas, 75235, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Vermont Lung Center, University of Vermont

Colchester, Vermont, 05446, United States

Location

University Physicians and Surgeons, Inc dba Marshall Health

Huntington, West Virginia, 25701, United States

Location

West Virginia Clinical and Translational Science Institute

Morgantown, West Virginia, 26506, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Motor Activity

Interventions

Educational Status

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Socioeconomic Factors; Population Characteristics

Study Officials

• Gary M Felker, MD

  Duke Clinical Research Institute

  STUDY CHAIR

• Barry Make, MD

  National Jewish Health

  STUDY CHAIR

• Lucinda Bateman, MD

  Bateman Horne Center

  STUDY CHAIR

• Janna Friedly, MD, MPH

  University of Washington

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 3, 2024
• First Posted: May 8, 2024
• Study Start: July 17, 2024
• Primary Completion: October 30, 2025
• Study Completion: October 30, 2025
• Last Updated: November 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (42)