RECOVER-AUTONOMIC Platform Protocol

NCT ID: NCT06305780

Last Updated: 2025-07-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

381 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-11

Study Completion Date

2025-07-09

Brief Summary

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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

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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.

Conditions

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Long COVID Long Covid19 Long Covid-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

In each Appendix trial, each participant will be assigned with equal probability to one of the factorial combinations based on two factors: (1) a study intervention/control and (2) non-pharmacologic intervention/control if the participant is eligible for the study intervention.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Double blind

Study Groups

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IVIG

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.

Group Type EXPERIMENTAL

IVIG + Coordinated Care

Intervention Type DRUG

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.

IVIG Placebo + Coordinated Care

Intervention Type DRUG

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.

IVIG + Usual Care

Intervention Type DRUG

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.

IVIG Placebo + Usual Care

Intervention Type DRUG

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.

Ivabradine

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.

Group Type EXPERIMENTAL

Ivabradine + Coordinated Care

Intervention Type DRUG

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.

Ivabradine Placebo + Coordinated Care

Intervention Type DRUG

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.

Ivabradine + Usual Care

Intervention Type DRUG

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.

Ivabradine Placebo + Usual Care

Intervention Type DRUG

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.

Interventions

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IVIG + Coordinated Care

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.

Intervention Type DRUG

IVIG Placebo + Coordinated Care

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.

Intervention Type DRUG

Ivabradine + Coordinated Care

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.

Intervention Type DRUG

Ivabradine Placebo + Coordinated Care

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.

Intervention Type DRUG

IVIG + Usual Care

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.

Intervention Type DRUG

IVIG Placebo + Usual Care

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.

Intervention Type DRUG

Ivabradine + Usual Care

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.

Intervention Type DRUG

Ivabradine Placebo + Usual Care

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.

Intervention Type DRUG

Eligibility Criteria

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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 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.
1. 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.
2. 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.
3. 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
4. OHQ/OIQ, question 1 score \>2

Exclusion Criteria

1. Known pregnancy, breast-feeding, or contemplating pregnancy during the study period
2. Known active acute SARS-CoV-2 infection ≤ 4 weeks from enrollment
3. Known renal failure (eGFR \<20ml/1.73 m²)
4. Known atrial fibrillation or significant cardiac arrhythmia
5. 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
6. Clinically significant atherosclerotic disease, defined as history of stroke or myocardial infarction or revascularization 6 months prior to enrollment and/or current symptomatic angina
7. Existing uncontrolled hypertension
8. History of significant hypercoagulability disorders
9. Active or recent thrombosis
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kanecia Obie Zimmerman

OTHER

Sponsor Role lead

Responsible Party

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Kanecia Obie Zimmerman

Associate Professor of Pediatrics

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Christopher Granger, MD

Role: STUDY_CHAIR

Duke Clinical Research Institute

Cyndya Shibao, MD

Role: STUDY_CHAIR

Vanderbilt University Medical Center

Peter Novak, MD

Role: STUDY_CHAIR

Harvard

Pam Taub, MD

Role: STUDY_CHAIR

University of California, San Diego

Tae Chung, MD

Role: STUDY_CHAIR

Johns Hopkins University

Locations

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East Alabama Medical Center - Appendix B Only

Opelika, Alabama, United States

Site Status

Center for Complex Neurology - Appendix A & B

Phoenix, Arizona, United States

Site Status

University of Arkansas for Medical Sciences - Appendix A & B

Little Rock, Arkansas, United States

Site Status

University of California San Diego - Appendix B Only

La Jolla, California, United States

Site Status

Cedars Sinai Medical Center - Appendix A & B

Los Angeles, California, United States

Site Status

Stanford University - Appendix B Only

Stanford, California, United States

Site Status

University of Colorado Anschutz Medical Campus Clinical and Translational Research Center (CTRC) - Appendix A & B

Aurora, Colorado, United States

Site Status

MedStar National Rehabilitation Hospital - Appendix B only

Washington D.C., District of Columbia, United States

Site Status

University of Florida Health - Appendix A & B

Gainesville, Florida, United States

Site Status

Lakeland Regional Medical Center - Appendix A & B

Lakeland, Florida, United States

Site Status

Innovation Clinical Trials Inc.- Appendix A & B

Palmetto Bay, Florida, United States

Site Status

Grady Memorial Hospital - Woodruff Memorial Research - Appendix A & B

Atlanta, Georgia, United States

Site Status

Morehouse School of Medicine - Appendix A & B

Atlanta, Georgia, United States

Site Status

Queens Medical Center - Appendix B Only

Honolulu, Hawaii, United States

Site Status

Rush University Medical Center - Appendix B Only

Chicago, Illinois, United States

Site Status

University of Illinois at Chicago - Appendix A & B

Chicago, Illinois, United States

Site Status

NorthShore University HealthSystem - Evanston Hospital - Appendix B Only

Evanston, Illinois, United States

Site Status

University of Iowa - Appendix A & B

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center CTSU Fairway - Appendix A & B

Fairway, Kansas, United States

Site Status

University of Kentucky Medical Center - Appendix A & B

Lexington, Kentucky, United States

Site Status

University Medical Center New Orleans - Appendix A & B

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Hospital - Appendix A Only

Baltimore, Maryland, United States

Site Status

Brigham and Women's Hospital - Appendix A Only

Boston, Massachusetts, United States

Site Status

Henry Ford Hospital - Appendix A & B

Detroit, Michigan, United States

Site Status

Mayo Clinic - Appendix A & B

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center - Appendix A & B

Jackson, Mississippi, United States

Site Status

Washington University School of Medicine - Appendix B Only

St Louis, Missouri, United States

Site Status

University at Buffalo - Appendix A & B

Buffalo, New York, United States

Site Status

St. Lawrence Health Medical Campus - Appendix A & B

Canton, New York, United States

Site Status

Columbia University Irving Medical Center - Appendix A & B

New York, New York, United States

Site Status

Stony Brook University Hospital - Appendix A & B

Stony Brook, New York, United States

Site Status

Montefiore Medical Center - Moses Campus - Appendix B

The Bronx, New York, United States

Site Status

Duke University Hospital - Appendix A & B

Durham, North Carolina, United States

Site Status

East Carolina University - Appendix B Only

Greenville, North Carolina, United States

Site Status

Cleveland Clinic - Appendix A & B

Cleveland, Ohio, United States

Site Status

University of Oklahoma Health Science Center - Oklahoma Clinical and Translational Science Institute - Appendix A & B

Oklahoma City, Oklahoma, United States

Site Status

Oregon Health and Science University - Appendix A & B

Portland, Oregon, United States

Site Status

Kent Hospital - Appendix A & B

Pawtucket, Rhode Island, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

National Neuromuscular Research Institute - Appendix A & B

Austin, Texas, United States

Site Status

Southwest Family Medicine Associates - Appendix A & B

Dallas, Texas, United States

Site Status

University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio - Appendix A & B

San Antonio, Texas, United States

Site Status

Bateman Horne Center - Appendix B Only

Salt Lake City, Utah, United States

Site Status

Vermont Lung Center, University of Vermont - Appendix B Only

Burlington, Vermont, United States

Site Status

University of Virginia Health System, University Hospital - Appendix A & B

Charlottesville, Virginia, United States

Site Status

Sentara Norfolk General Hospital - Appendix A & B

Norfolk, Virginia, United States

Site Status

Evergreen Hospital Medical Center - Appendix A & B

Kirkland, Washington, United States

Site Status

Providence Medical Research Center - Appendix A & B

Spokane, Washington, United States

Site Status

Marshall Health - University Physicians and Surgeons - Appendix A & B

Huntington, West Virginia, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Informed Consent Form

View Document

Related Links

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Other Identifiers

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OTA-21-015G

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00112597

Identifier Type: -

Identifier Source: org_study_id

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