RECOVER-AUTONOMIC Platform Protocol

Kanecia Obie Zimmerman

Status and phase: Enrolling; Phase 2

Conditions: Long Covid19; Long Covid-19; Long COVID

Treatments: Drug: Ivabradine Placebo + Coordinated Care; Drug: IVIG + Usual Care; Drug: IVIG + Coordinated Care; Drug: Ivabradine + Usual Care; Drug: IVIG Placebo + Coordinated Care; Drug: Ivabradine + Coordinated Care; Drug: Ivabradine Placebo + Usual Care; Drug: IVIG Placebo + Usual Care

Study type: Interventional

Funder types: Other

Identifiers

NCT06305780

Pro00112597

OTA-21-015G (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 380 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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380 participants in 2 patient groups

IVIG

Experimental group

Description:

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.

Treatment:

Drug: IVIG Placebo + Usual Care

Drug: IVIG Placebo + Coordinated Care

Drug: IVIG + Coordinated Care

Drug: IVIG + Usual Care

Ivabradine

Experimental group

Description:

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.

Treatment:

Drug: Ivabradine Placebo + Usual Care

Drug: Ivabradine + Coordinated Care

Drug: Ivabradine + Usual Care

Drug: Ivabradine Placebo + Coordinated Care