Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
N/A
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
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 Purpose
Treatment
Masking
Single (Outcomes Assessor)
Masking Description
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)

Arm Groups

ArmDescriptionAssigned Intervention
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.

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35205

Banner University Medical Center Phoenix
Phoenix, Arizona 85006

Banner University Medical Center Tucson
Tucson, Arizona 85719

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Torrance, California 90509

Yale - New Haven Hospital
New Haven, Connecticut 06520-8017

University of Florida College of Medicine Jacksonville
Jacksonville, Florida 32209

Grady Memorial Hospital (Emory)
Atlanta, Georgia 30303

Emory Hope Clinic
Decatur, Georgia 30030

University of Illinois at Chicago
Chicago, Illinois 60608

North Shore University HealthSystem/Evanston Hospital
Evanston, Illinois 60201

Saint Francis Medical Center
Peoria, Illinois 61637

Cedar Valley Clinical Research
Waterloo, Iowa 50701
Contact:
Sarah Larson, RN, BSN
319-888-8270
slarson@cvmspc.com

Maine Health Institute of Research
Scarborough, Maine 04074

Tufts Medical Center
Boston, Massachusetts 02111

Beth Israel Deaconess Med. Ctr.
Boston, Massachusetts 02215

Henry Ford Hospital
Detroit, Michigan 48202
Contact:
Crystal Grimshaw
cgrimsh1@hfhs.org

Mayo Clinic
Rochester, Minnesota 55905

Washington University School of Medicine
Saint Louis, Missouri 63110

University of New Mexico Health Sciences Center
Albuquerque, New Mexico 87102

University of North Carolina Hospital
Chapel Hill, North Carolina 27514

University of Pittsburgh
Pittsburgh, Pennsylvania 15213

Avera McKennan Hospital & University Health Center
Sioux Falls, South Dakota 57108
Contact:
Sophie Two Hawk, MD
ClinicalResearch@avera.org

Southwest Family Medicine Associates
Dallas, Texas 75235

Houston Methodist Hospital
Houston, Texas 77030

University of Texas Health Science Center at Houston
Houston, Texas 77030

University of Utah
Salt Lake City, Utah 84132

Vermont Lung Center, University of Vermont
Colchester, Vermont 05446

West Virginia Clinical and Translational Science Institute
Morgantown, West Virginia 26506

More Details

NCT ID
NCT06404047
Status
Recruiting
Sponsor
Duke University

Study Contact

Nilda Itchon-Ramos
919-668-8060
recoverresearch@duke.edu

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.