Clinical trial NCT06305780: RECOVER-AUTONOMIC Platform Protocol
Official title: RECOVER-AUTONOMIC: A Platform Protocol for Evaluation of Interventions for Autonomic Dysfunction in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Long COVID
Long Covid19
Long Covid-19
Keywords: PASC
POTS
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2024-03-12
Enrollment: 380
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Total number of participants enrolled in each Appendix
timeFrame: Baseline to End of Intervention (IVIG 9 months, Ivabradine 3 months)
Secondary outcomes:
Other outcomes:
Locations:
city: Opelika
country: United States
facility: East Alabama Medical Center - Appendix B Only
state: Alabama
city: Phoenix
country: United States
facility: Center for Complex Neurology - Appendix A & B
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences - Appendix A & B
state: Arkansas
city: La Jolla
country: United States
facility: University of California San Diego - Appendix B Only
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center - Appendix A & B
state: California
city: Stanford
country: United States
facility: Stanford University - Appendix B Only
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus Clinical and Translational Research Center (CTRC) - Appendix A & B
state: Colorado
city: Washington
country: United States
facility: MedStar National Rehabilitation Hospital - Appendix B only
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida Health - Appendix A & B
state: Florida
city: Lakeland
country: United States
facility: Lakeland Regional Medical Center - Appendix A & B
state: Florida
city: Palmetto Bay
country: United States
facility: Innovation Clinical Trials Inc.- Appendix A & B
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital - Woodruff Memorial Research - Appendix A & B
state: Georgia
city: Atlanta
country: United States
facility: Morehouse School of Medicine - Appendix A & B
state: Georgia
city: Honolulu
country: United States
facility: Queens Medical Center - Appendix B Only
state: Hawaii
city: Chicago
country: United States
facility: Rush University Medical Center - Appendix B Only
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago - Appendix A & B
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem - Evanston Hospital - Appendix B Only
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa - Appendix A & B
state: Iowa
city: Fairway
country: United States
facility: University of Kansas Medical Center CTSU Fairway - Appendix A & B
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Medical Center - Appendix A & B
state: Kentucky
city: New Orleans
country: United States
facility: University Medical Center New Orleans - Appendix A & B
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital - Appendix A Only
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital - Appendix A Only
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital - Appendix A & B
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Appendix A & B
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center - Appendix A & B
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Appendix B Only
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus - Appendix B
state: New York
city: Buffalo
country: United States
facility: University at Buffalo - Appendix A & B
state: New York
city: Canton
country: United States
facility: St. Lawrence Health Medical Campus - Appendix A & B
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center - Appendix A & B
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital - Appendix A & B
state: New York
city: Durham
country: United States
facility: Duke University Hospital - Appendix A & B
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University - Appendix B Only
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic - Appendix A & B
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Science Center - Oklahoma Clinical and Translational Science Institute - Appendix A & B
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University - Appendix A & B
state: Oregon
city: Pawtucket
country: United States
facility: Kent Hospital - Appendix A & B
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: National Neuromuscular Research Institute - Appendix A & B
state: Texas
city: Dallas
country: United States
facility: Southwest Family Medicine Associates - Appendix A & B
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio - Appendix A & B
state: Texas
city: Salt Lake City
country: United States
facility: Bateman Horne Center - Appendix B Only
state: Utah
city: Burlington
country: United States
facility: Vermont Lung Center, University of Vermont - Appendix B Only
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Health System, University Hospital - Appendix A & B
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital - Appendix A & B
state: Virginia
city: Kirkland
country: United States
facility: Evergreen Hospital Medical Center - Appendix A & B
state: Washington
city: Spokane
country: United States
facility: Providence Medical Research Center - Appendix A & B
state: Washington
city: Huntington
country: United States
facility: Marshall Health - University Physicians and Surgeons - Appendix A & B
state: West Virginia
Study officials:
affiliation: Duke Clinical Research Institute
name: Christopher Granger, MD
role: STUDY_CHAIR
affiliation: Vanderbilt University Medical Center
name: Cyndya Shibao, MD
role: STUDY_CHAIR
affiliation: Harvard
name: Peter Novak, MD
role: STUDY_CHAIR
affiliation: University of California, San Diego
name: Pam Taub, MD
role: STUDY_CHAIR
affiliation: Johns Hopkins University
name: Tae Chung, MD
role: STUDY_CHAIR
References: