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Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
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
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
Double blind

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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.
  • Drug: 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.
  • 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.
  • 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.
  • 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.
Experimental
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.
  • 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.
  • 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.
  • 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.
  • 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.

Recruiting Locations

More Details

NCT ID
NCT06305780
Status
Enrolling by invitation
Sponsor
Kanecia Obie Zimmerman

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.