This is a platform protocol designed to be flexible so that it is suitable for a range ofinterventions and settings within diverse health care systems and community settings withincorporation into clinical COVID-19 management programs and treatment plans if resultsachieve key study outcomes.This protocol is a prospective, multi-center, multi-arm, randomized, controlled platformtrial evaluating interventions to address and improve exercise intolerance andpost-exertional malaise (PEM) as manifestations of Post-Acute Sequelae of SARS-CoV-2Infection (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 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.
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.
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: 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.
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.
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.
University of Alabama at Birmingham
Birmingham 4049979, Alabama 4829764, United States
Banner University Medical Center Phoenix
Phoenix 5308655, Arizona 5551752, United States
Banner University Medical Center Tucson
Tucson 5318313, Arizona 5551752, United States
Stanford University
Stanford 5398563, California 5332921, United States
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Torrance 5403022, California 5332921, United States
University of Colorado
Aurora 5412347, Colorado 5417618, United States
Yale - New Haven Hospital
New Haven 4839366, Connecticut 4831725, United States
University of Florida College of Medicine Jacksonville
Jacksonville 4160021, Florida 4155751, United States
Innovation Clinical Trials Inc.
Miami 4164138, Florida 4155751, United States
Valencia Medical and Research Center
Miami 4164138, Florida 4155751, United States
Grady Memorial Hospital (Emory)
Atlanta 4180439, Georgia 4197000, United States
Emory Hope Clinic
Decatur 4191124, Georgia 4197000, United States
University of Illinois at Chicago
Chicago 4887398, Illinois 4896861, United States
Rush University Medical Center
Chicago 4887398, Illinois 4896861, United States
North Shore University HealthSystem/Evanston Hospital
Evanston 4891382, Illinois 4896861, United States
Saint Francis Medical Center
Peoria 4905687, Illinois 4896861, United States
Cedar Valley Clinical Research
Waterloo 4880889, Iowa 4862182, United States
Kansas University Medical Center
Kansas City 4273837, Kansas 4273857, United States
University of Kentucky
Lexington 4297983, Kentucky 6254925, United States
Maine Health Institute of Research
Scarborough 4977882, Maine 4971068, United States
Tufts Medical Center
Boston 4930956, Massachusetts 6254926, United States
Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926, United States
Brigham and Women's Hospital
Boston 4930956, Massachusetts 6254926, United States
Beth Israel Deaconess Med. Ctr.
Boston 4930956, Massachusetts 6254926, United States
Henry Ford Hospital
Detroit 4990729, Michigan 5001836, United States
Mayo Clinic
Rochester 5043473, Minnesota 5037779, United States
Washington University School of Medicine
St Louis 4407066, Missouri 4398678, United States
Dartmouth Hitchcock Medical Center
Lebanon 5088597, New Hampshire 5090174, United States
University of New Mexico Health Sciences Center
Albuquerque 5454711, New Mexico 5481136, United States
NYU Langone Health/Brooklyn Hospital
Brooklyn 5110302, New York 5128638, United States
University of North Carolina Hospital
Chapel Hill 4460162, North Carolina 4482348, United States
Duke University Medical Center
Durham 4464368, North Carolina 4482348, United States
Oregon Health and Science University
Portland 5746545, Oregon 5744337, United States
University of Pittsburgh
Pittsburgh 5206379, Pennsylvania 6254927, United States
Avera McKennan Hospital & University Health Center
Sioux Falls 5231851, South Dakota 5769223, United States
Southwest Family Medicine Associates
Dallas 4684888, Texas 4736286, United States
Houston Methodist Hospital
Houston 4699066, Texas 4736286, United States
University of Texas Health Science Center at Houston
Houston 4699066, Texas 4736286, United States
University of Utah
Salt Lake City 5780993, Utah 5549030, United States
Vermont Lung Center, University of Vermont
Colchester 5235024, Vermont 5242283, United States
University Physicians and Surgeons, Inc dba Marshall Health
Huntington 4809537, West Virginia 4826850, United States
West Virginia Clinical and Translational Science Institute
Morgantown 4815352, West Virginia 4826850, United States
Nilda Itchon-Ramos
919-668-8060
recoverresearch@duke.edu
Barrie Harper
recoverresearch@duke.edu