RECOVER-AUTONOMIC Platform Protocol
- Conditions
- Long COVIDLong Covid19Long Covid-19
- Interventions
- Drug: IVIG + Coordinated CareDrug: IVIG Placebo + Coordinated CareDrug: IVIG + Usual CareDrug: IVIG Placebo + Usual Care
- Registration Number
- NCT06305780
- Lead Sponsor
- Kanecia Obie Zimmerman
- 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.
- Detailed Description
The hypothesis is that some of the autonomic dysfunction symptoms are immune-mediated, so immunotherapy and other applicable therapies will result in improvement in autonomic symptoms.
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 380
-
≥ 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 >25) 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
- 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, symptomatic ischemic coronary artery disease, revascularization for PAD/CAD within the past 6 months
- 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
- History of significant hypercoagulability disorders
- Active or recent thrombosis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ivabradine Ivabradine + Usual Care In 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. IVIG IVIG + Coordinated Care In 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. IVIG IVIG Placebo + Coordinated Care In 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. IVIG IVIG + Usual Care In 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. IVIG IVIG Placebo + Usual Care In 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 Ivabradine + Coordinated Care In 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. Ivabradine Ivabradine Placebo + Coordinated Care In 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. Ivabradine Ivabradine Placebo + Usual Care In 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.
- Primary Outcome Measures
Name Time Method Total number of participants enrolled in each Appendix Baseline to End of Intervention (IVIG 9 months, Ivabradine 3 months) Total number of participants enrolled in each Appendix will be reported. Appendix-specific outcome measure data will be reported under the associated NCT#
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (50)
Duke University Hospital - Appendix A & B
🇺🇸Durham, North Carolina, United States
East Alabama Medical Center - Appendix B Only
🇺🇸Opelika, Alabama, United States
Center for Complex Neurology - Appendix A & B
🇺🇸Phoenix, Arizona, United States
University of Arkansas for Medical Sciences - Appendix A & B
🇺🇸Little Rock, Arkansas, United States
University of California San Diego - Appendix B Only
🇺🇸La Jolla, California, United States
Cedars Sinai Medical Center - Appendix A & B
🇺🇸Los Angeles, California, United States
Stanford University - Appendix B Only
🇺🇸Stanford, California, United States
University of Colorado Anschutz Medical Campus Clinical and Translational Research Center (CTRC) - Appendix A & B
🇺🇸Aurora, Colorado, United States
MedStar National Rehabilitation Hospital - Appendix B only
🇺🇸Washington, District of Columbia, United States
University of Florida Health - Appendix A & B
🇺🇸Gainesville, Florida, United States
Lakeland Regional Medical Center - Appendix A & B
🇺🇸Lakeland, Florida, United States
Innovation Clinical Trials Inc.- Appendix A & B
🇺🇸Palmetto Bay, Florida, United States
Grady Memorial Hospital - Woodruff Memorial Research - Appendix A & B
🇺🇸Atlanta, Georgia, United States
Morehouse School of Medicine - Appendix A & B
🇺🇸Atlanta, Georgia, United States
Queens Medical Center - Appendix B Only
🇺🇸Honolulu, Hawaii, United States
Rush University Medical Center - Appendix B Only
🇺🇸Chicago, Illinois, United States
University of Illinois at Chicago - Appendix A & B
🇺🇸Chicago, Illinois, United States
NorthShore University HealthSystem - Evanston Hospital - Appendix B Only
🇺🇸Evanston, Illinois, United States
University of Iowa - Appendix A & B
🇺🇸Iowa City, Iowa, United States
University of Kansas Medical Center CTSU Fairway - Appendix A & B
🇺🇸Fairway, Kansas, United States
University of Kentucky Medical Center - Appendix A & B
🇺🇸Lexington, Kentucky, United States
University Medical Center New Orleans - Appendix A & B
🇺🇸New Orleans, Louisiana, United States
Johns Hopkins Hospital - Appendix A Only
🇺🇸Baltimore, Maryland, United States
Brigham and Women's Hospital - Appendix A Only
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital - Appendix A & B
🇺🇸Detroit, Michigan, United States
Mayo Clinic - Appendix A & B
🇺🇸Rochester, Minnesota, United States
University of Mississippi Medical Center - Appendix A & B
🇺🇸Jackson, Mississippi, United States
Washington University School of Medicine - Appendix B Only
🇺🇸Saint Louis, Missouri, United States
Montefiore Medical Center - Moses Campus - Appendix B
🇺🇸Bronx, New York, United States
University at Buffalo - Appendix A & B
🇺🇸Buffalo, New York, United States
St. Lawrence Health Medical Campus - Appendix A & B
🇺🇸Canton, New York, United States
Columbia University Irving Medical Center - Appendix A & B
🇺🇸New York, New York, United States
Stony Brook University Hospital - Appendix A & B
🇺🇸Stony Brook, New York, United States
East Carolina University - Appendix B Only
🇺🇸Greenville, North Carolina, United States
Cleveland Clinic - Appendix A & B
🇺🇸Cleveland, Ohio, United States
University of Oklahoma Health Science Center - Oklahoma Clinical and Translational Science Institute - Appendix A & B
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health and Science University - Appendix A & B
🇺🇸Portland, Oregon, United States
Kent Hospital - Appendix A & B
🇺🇸Pawtucket, Rhode Island, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
National Neuromuscular Research Institute - Appendix A & B
🇺🇸Austin, Texas, United States
Southwest Family Medicine Associates - Appendix A & B
🇺🇸Dallas, Texas, United States
University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
University of Texas Health Science Center at San Antonio - Appendix A & B
🇺🇸San Antonio, Texas, United States
Bateman Horne Center - Appendix B Only
🇺🇸Salt Lake City, Utah, United States
Vermont Lung Center, University of Vermont - Appendix B Only
🇺🇸Burlington, Vermont, United States
University of Virginia Health System, University Hospital - Appendix A & B
🇺🇸Charlottesville, Virginia, United States
Sentara Norfolk General Hospital - Appendix A & B
🇺🇸Norfolk, Virginia, United States
Evergreen Hospital Medical Center - Appendix A & B
🇺🇸Kirkland, Washington, United States
Providence Medical Research Center - Appendix A & B
🇺🇸Spokane, Washington, United States
Marshall Health - University Physicians and Surgeons - Appendix A & B
🇺🇸Huntington, West Virginia, United States