RECOVER-AUTONOMIC Platform Protocol
RECOVER-AUTONOMIC: A Platform Protocol for Evaluation of Interventions for Autonomic Dysfunction in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)
2 other identifiers
interventional
381
1 country
50
Brief Summary
This study is a platform protocol designed to be flexible so that it is suitable for a wide range of settings within health care systems and in community settings where it can be integrated into COVID-19 programs and subsequent treatment plans. This protocol is a prospective, multi-center, multi-arm, randomized, controlled platform trial evaluating various interventions for use in the treatment of autonomic dysfunction symptoms, including cardiovascular complications and postural orthostatic tachycardia syndrome (POTS), in PASC participants. The interventions tested will include non-pharmacologic care and pharmacologic therapies with study drugs.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2024
Shorter than P25 for phase_2
50 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 4, 2024
CompletedStudy Start
First participant enrolled
March 11, 2024
CompletedFirst Posted
Study publicly available on registry
March 12, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 9, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
July 9, 2025
CompletedFebruary 20, 2026
February 1, 2026
1.3 years
March 4, 2024
February 18, 2026
Conditions
Keywords
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#
Baseline to End of Intervention (IVIG 9 months, Ivabradine 3 months)
Study Arms (2)
IVIG
EXPERIMENTALIn the IVIG study, randomization will be implemented with 1:1:1:1 allocation among the combination of IVIG/placebo and coordinated/ usual non-pharmacologic care. All participants will receive IVIG or placebo for 9 months (36 weeks) with a follow-up period for an additional 3 months (total study duration for 12 months). See NCT06305793 for additional details.
Ivabradine
EXPERIMENTALIn the ivabradine study, randomization will be implemented with 1:1:1:1 allocation among the combinations of ivabradine/placebo and coordinated/usual care. All participants receive either ivabradine or placebo for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months). See NCT06305806 for additional details.
Interventions
Participants will receive IVIG for a duration of 9 months and coordinated non-pharmacologic care for a duration of 3 months, concurrent with IVIG administration. Coordinated non-pharmacologic care involves volume expansion through high salt diet, water intake, abdominal binder, exercise/rehabilitation, motivation, education, and assisted care through a care coordinator.
Normal saline given intravenously will be the control (placebo) product. Blinding IV bag and tubing covers will be used for both IVIG and Placebo administration. Participants will receive IVIG placebo for a duration of 9 months and coordinated non-pharmacologic care for a duration of 3 months, concurrent with IVIG placebo administration. Coordinated non-pharmacologic care involves volume expansion through high salt diet, water intake, abdominal binder, exercise/rehabilitation, motivation, education, and assisted care through a care coordinator.
Participants will receive IVIG for a duration of 9 months and usual non-pharmacologic care (control) for a duration of 3 months. This will be concurrent with scheduled IVIG administration.
Participants will receive Ivabradine for a duration of 3 months and coordinated non-pharmacologic care for a duration of 3 months, concurrent with ivabradine administration. Coordinated non-pharmacologic care involves volume expansion through high salt diet, water intake, abdominal binder, exercise/rehabilitation, motivation, education, and assisted care through care coordinator.
The control (placebo) oral tablets will be similar to the study drug, ivabradine. The control packaging matches the packaging. Participants will receive Ivabradine placebo for a duration of 3 months and coordinated non-pharmacologic care for a duration of 3 months, concurrent with ivabradine placebo administration. Coordinated non-pharmacologic care involves volume expansion through high salt diet, water intake, abdominal binder, exercise/rehabilitation, feedback, nutrition counseling, motivation, education, and assisted care through care coordinator.
Normal saline given intravenously will be the control (placebo) product. The normal saline will be of similar formulation and appearance to IVIG. Participants will receive IVIG placebo for a duration of 9 months and usual non-pharmacologic care (control) for a duration of 3 months. This will be concurrent with scheduled IVIG placebo administration.
Participants will receive Ivabradine for a duration of 3 months and usual non-pharmacologic care (control) for a duration of 3 months, concurrent with ivabradine administration.
The control (placebo) oral tablets will be similar to the study drug, ivabradine. The control packaging matches the packaging. Participants will receive Ivabradine placebo for a duration of 3 months and usual non-pharmacologic care (control) for a duration of 3 months, concurrent with ivabradine placebo administration.
Eligibility Criteria
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 Organization12ɸ ɸ Enrollment of participants with suspected or probable SARS-CoV-2 infection will only be allowed if they occurred before May 1, 2021 and be limited to no more than 10% of the total sample size per Study Drug Appendix. Refer to the Manual of Procedures (MOP) for details.
- Suspected case of SARS-CoV-2 infection - Three options, A through C:
- A. 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. Presents with 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. Presents 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, defined as 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 through 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 suspect case A). With a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.
- Moderate, self-identified autonomic symptoms (defined as COMPASS-31 \>20) following a SARS-CoV-2 infection that has persisted for at least 12 weeks and is still present at the time of consent
- OHQ/OIQ, question 1 score \>2
You may not qualify if:
- Known pregnancy, breast-feeding, or contemplating pregnancy during the study period
- Known active acute SARS-CoV-2 infection ≤ 4 weeks from enrollment
- Known renal failure (eGFR \<20ml/1.73 m²)
- Known atrial fibrillation or significant cardiac arrhythmia
- Known cardiovascular conditions such as heart failure (Class 3-4), severe valvular disease
- Clinically significant atherosclerotic disease, defined as history of stroke or myocardial infarction or revascularization 6 months prior to enrollment and/or current symptomatic angina
- Existing uncontrolled hypertension
- Inability to comply with the protocol
- Any condition that the investigator believes makes it inappropriate to treat with study intervention, including severe debility.
- History of POTS or significant dysautonomia before COVID-19 index infection
- Enrolled in another clinical trial or another study intervention appendix in this platform protocol \* Patients who are a part of observational studies (e.g. imaging) may be included in this trial. Participants may enroll in another interventional trial or re-enroll in this trial for a different study intervention appendix 30 days after end of study (Follow-up visit).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (50)
East Alabama Medical Center - Appendix B Only
Opelika, Alabama, 36801, United States
Center for Complex Neurology - Appendix A & B
Phoenix, Arizona, 85006, United States
University of Arkansas for Medical Sciences - Appendix A & B
Little Rock, Arkansas, 72205, United States
University of California San Diego - Appendix B Only
La Jolla, California, 92307, United States
Cedars Sinai Medical Center - Appendix A & B
Los Angeles, California, 90048, United States
Stanford University - Appendix B Only
Stanford, California, 94305, United States
University of Colorado Anschutz Medical Campus Clinical and Translational Research Center (CTRC) - Appendix A & B
Aurora, Colorado, 80045, United States
MedStar National Rehabilitation Hospital - Appendix B only
Washington D.C., District of Columbia, 20010, United States
University of Florida Health - Appendix A & B
Gainesville, Florida, 32610, United States
Lakeland Regional Medical Center - Appendix A & B
Lakeland, Florida, 33805, United States
Innovation Clinical Trials Inc.- Appendix A & B
Palmetto Bay, Florida, 33157, United States
Grady Memorial Hospital - Woodruff Memorial Research - Appendix A & B
Atlanta, Georgia, 30303, United States
Morehouse School of Medicine - Appendix A & B
Atlanta, Georgia, 30310, United States
Queens Medical Center - Appendix B Only
Honolulu, Hawaii, 96813, United States
Rush University Medical Center - Appendix B Only
Chicago, Illinois, 60612, United States
University of Illinois at Chicago - Appendix A & B
Chicago, Illinois, 60612, United States
NorthShore University HealthSystem - Evanston Hospital - Appendix B Only
Evanston, Illinois, 60201, United States
University of Iowa - Appendix A & B
Iowa City, Iowa, 52242, United States
University of Kansas Medical Center CTSU Fairway - Appendix A & B
Fairway, Kansas, 66205, United States
University of Kentucky Medical Center - Appendix A & B
Lexington, Kentucky, 40536, United States
University Medical Center New Orleans - Appendix A & B
New Orleans, Louisiana, 70112, United States
Johns Hopkins Hospital - Appendix A Only
Baltimore, Maryland, 21287, United States
Brigham and Women's Hospital - Appendix A Only
Boston, Massachusetts, 02115, United States
Henry Ford Hospital - Appendix A & B
Detroit, Michigan, 48202, United States
Mayo Clinic - Appendix A & B
Rochester, Minnesota, 55905, United States
University of Mississippi Medical Center - Appendix A & B
Jackson, Mississippi, 39216, United States
Washington University School of Medicine - Appendix B Only
St Louis, Missouri, 63110, United States
University at Buffalo - Appendix A & B
Buffalo, New York, 14203, United States
St. Lawrence Health Medical Campus - Appendix A & B
Canton, New York, 13617, United States
Columbia University Irving Medical Center - Appendix A & B
New York, New York, 10032, United States
Stony Brook University Hospital - Appendix A & B
Stony Brook, New York, 11794, United States
Montefiore Medical Center - Moses Campus - Appendix B
The Bronx, New York, 10467, United States
Duke University Hospital - Appendix A & B
Durham, North Carolina, 27710, United States
East Carolina University - Appendix B Only
Greenville, North Carolina, 27834, United States
Cleveland Clinic - Appendix A & B
Cleveland, Ohio, 44195, United States
University of Oklahoma Health Science Center - Oklahoma Clinical and Translational Science Institute - Appendix A & B
Oklahoma City, Oklahoma, 73104, United States
Oregon Health and Science University - Appendix A & B
Portland, Oregon, 97239, United States
Kent Hospital - Appendix A & B
Pawtucket, Rhode Island, 02860, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
National Neuromuscular Research Institute - Appendix A & B
Austin, Texas, 78759, United States
Southwest Family Medicine Associates - Appendix A & B
Dallas, Texas, 75235, United States
University of Texas Health Science Center at Houston
Houston, Texas, 78701, United States
University of Texas Health Science Center at San Antonio - Appendix A & B
San Antonio, Texas, 78229, United States
Bateman Horne Center - Appendix B Only
Salt Lake City, Utah, 84102, United States
Vermont Lung Center, University of Vermont - Appendix B Only
Burlington, Vermont, 05405, United States
University of Virginia Health System, University Hospital - Appendix A & B
Charlottesville, Virginia, 22908, United States
Sentara Norfolk General Hospital - Appendix A & B
Norfolk, Virginia, 23507, United States
Evergreen Hospital Medical Center - Appendix A & B
Kirkland, Washington, 98034, United States
Providence Medical Research Center - Appendix A & B
Spokane, Washington, 99204, United States
Marshall Health - University Physicians and Surgeons - Appendix A & B
Huntington, West Virginia, 25701, United States
Related Publications (1)
Fudim M, Novak P, Taub PR, Chung T, Zimmerman KO, Moy OV, Fissler HZ, Wen J, Freeman NLB, O'Brien S, Marti H, Cook D, Low P, Kim DY, Rosenberg Y, Granger CB, Shibao CA. Design and rationale of RECOVER-AUTONOMIC: A randomized platform trial evaluating interventions for Long COVID postural orthostatic tachycardia syndrome. Am Heart J. 2026 Jun;296:107384. doi: 10.1016/j.ahj.2026.107384. Epub 2026 Feb 18.
PMID: 41720282DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Christopher Granger, MD
Duke Clinical Research Institute
- STUDY CHAIR
Cyndya Shibao, MD
Vanderbilt University Medical Center
- STUDY CHAIR
Peter Novak, MD
Harvard
- STUDY CHAIR
Pam Taub, MD
University of California, San Diego
- STUDY CHAIR
Tae Chung, MD
Johns Hopkins University
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- Double blind
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Associate Professor of Pediatrics
Study Record Dates
First Submitted
March 4, 2024
First Posted
March 12, 2024
Study Start
March 11, 2024
Primary Completion
July 9, 2025
Study Completion
July 9, 2025
Last Updated
February 20, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will not share
The summary of results will be shared on the study website: https://recovercovid.org/