RECOVER-ENERGIZE Platform Protocol

RECOVER-ENERGIZE: A Platform Protocol for Evaluation of Interventions for Exercise Intolerance in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)

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.

Study Overview

• Status: Completed
• Conditions: Long COVID; Long Covid19; Long Covid-19
• Intervention / Treatment: Behavioral: Personalized Cardiopulmonary Rehabilitation; Other: Education; Behavioral: Structured Pacing; Other: Usual Care

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 Type: Interventional
• Enrollment (Actual): 660
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center Phoenix
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center Tucson
  • California
    • Stanford, California, United States, 94035
      • Stanford University
    • Torrance, California, United States, 90509
      • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8017
      • Yale - New Haven Hospital
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida College of Medicine Jacksonville
    • Miami, Florida, United States, 33165
      • Valencia Medical and Research Center
    • Miami, Florida, United States, 33144
      • Innovation Clinical Trials Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Memorial Hospital (Emory)
    • Decatur, Georgia, United States, 30030
      • Emory Hope Clinic
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60608
      • University of Illinois at Chicago
    • Evanston, Illinois, United States, 60201
      • North Shore University HealthSystem/Evanston Hospital
    • Peoria, Illinois, United States, 61637
      • Saint Francis Medical Center
  • Iowa
    • Waterloo, Iowa, United States, 50701
      • Cedar Valley Clinical Research
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University Of Kentucky
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Health Institute of Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Med. Ctr.
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Health Sciences Center
  • New York
    • Brooklyn, New York, United States, 11220
      • NYU Langone Health/Brooklyn Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina Hospital
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Oregon Health and Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57108
      • Avera McKennan Hospital & University Health Center
  • Texas
    • Dallas, Texas, United States, 75235
      • Southwest Family Medicine Associates
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Vermont
    • Colchester, Vermont, United States, 05446
      • Vermont Lung Center, University of Vermont
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • University Physicians and Surgeons, Inc dba Marshall Health
    • Morgantown, West Virginia, United States, 26506
      • West Virginia Clinical and Translational Science Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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
Experimental: 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.	Behavioral: 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.; Other: 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.
Experimental: 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.	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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Study Chair: 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

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2024
• Primary Completion (Actual): October 30, 2025
• Study Completion (Actual): October 30, 2025

Study Registration Dates

• First Submitted: May 3, 2024
• First Submitted That Met QC Criteria: May 6, 2024
• First Posted (Actual): May 8, 2024

Study Record Updates

• Last Update Posted (Estimated): November 14, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Exercise; PASC; PEM (post exertional malaise)
• Additional Relevant MeSH Terms: Post-Infectious Disorders; COVID-19; Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Pathological Conditions, Signs and Symptoms; Behavior; Post-Acute COVID-19 Syndrome; Motor Activity; Socioeconomic Factors; Population Characteristics; Educational Status
• Other Study ID Numbers: Pro00112409; OT2HL156812 (U.S. NIH Grant/Contract); NHLBI Grant to RTI (Other Grant/Funding Number: RTI subcontracting with DCRI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The summary of the results will be shared on the study website: https://recovercovid.org/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No