RECOVER-AUTONOMIC: Platform Protocol, Appendix B (Ivabradine)

NCT ID: NCT06305806

Last Updated: 2025-10-21

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

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

181 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-11

Study Completion Date

2025-12-31

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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Ivabradine + Coordinated Care

The starting dose will be 5 mg twice a day, and the dose will be modified if needed at the 1 month clinic visit. At this visit, HR will be measured and the dose will be modified as applicable. The maximum dose will be 7.5 mg twice daily if HR is ˃ 90 bpm.

The table below provides the dosing of ivabradine based on HR.

Supine Resting HR 60-80 2.5 mg BID Supine Resting HR \>80 5 mg BID Supine Resting HR \>90 7.5 mg BID

\*Resting HR should be measured 5 minutes after lying down

Group Type EXPERIMENTAL

Ivabradine

Intervention Type DRUG

Participants will receive ivabradine for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months).

Coordinated Care

Intervention Type BEHAVIORAL

Participants will receive 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

Group Type EXPERIMENTAL

Ivabradine Placebo

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 placebo for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months).

Coordinated Care

Intervention Type BEHAVIORAL

Participants will receive 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 + Usual Care

The starting dose will be 5 mg twice a day, and the dose will be modified if needed at the 1 month clinic visit. At this visit, HR will be measured and the dose will be modified as applicable. The maximum dose will be 7.5 mg twice daily if HR is ˃ 90 bpm.

The table below provides the dosing of ivabradine based on HR.

Supine Resting HR 60-80 2.5 mg BID Supine Resting HR \>80 5 mg BID Supine Resting HR \>90 7.5 mg BID

\*Resting HR should be measured 5 minutes after lying down

Group Type EXPERIMENTAL

Ivabradine

Intervention Type DRUG

Participants will receive ivabradine for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months).

Usual Care

Intervention Type BEHAVIORAL

Participants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with ivabradine administration.

Ivabradine Placebo + Usual Care

Group Type EXPERIMENTAL

Ivabradine Placebo

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 placebo for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months).

Usual Care

Intervention Type BEHAVIORAL

Participants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with ivabradine administration.

Interventions

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Ivabradine

Participants will receive ivabradine for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months).

Intervention Type DRUG

Ivabradine Placebo

The control (placebo) oral tablets will be similar to the study drug, ivabradine.

The control packaging matches the packaging.

Participants will receive placebo for 3 months (12 weeks) with a follow-up period for an additional 3 months (total study duration of 6 months).

Intervention Type DRUG

Coordinated Care

Participants will receive 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 BEHAVIORAL

Usual Care

Participants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with ivabradine administration.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

1. Abnormal active standing test defined as presence of orthostatic tachycardia (an increase of 30 beats per minute (bpm) or more in HR within 10 minutes upon standing without orthostatic hypotension) and experiencing orthostatic symptoms
2. COMPASS-31 Score \> 25 and not enrolled in the IVIG appendix

Exclusions Criteria:

Exclusion Criteria

1. A person of child-bearing potential who is not taking effective contraception
2. Use of the following medications: clonidine, tizanidine, amphetamines, and serotonin and norepinephrine reuptake inhibitors (SNRIs) with the exception of modafinil
3. Use of beta-blockers (any formulation), calcium channel blockers, midodrine, pyridostigmine, fludrocortisone, and guanfacine will be excluded unless participant is on a stable dose (\>4 weeks). Participants on stable doses will be allowed to continue the medication throughout the study.
4. Combination with verapamil or diltiazem which are moderate CYP3A4 inhibitors with heart rate reducing properties
5. Lactating and breast-feeding women
6. Severe hepatic impairment
7. Use of drugs known to prolong the QT-interval (e.g., quinidine, disopyramide, bepridil, sotalol, amiodarone, pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine
8. Concomitant use of digoxin
9. Participants who are pacemaker dependent
10. Patients with hypokalemia (serum K+\<3.5 mEq/L)
11. Patients taking potassium-depleting diuretics
12. A history of congenital or acquired long QT syndrome, with or without torsade de pointes
13. Patients with high degree AV block such as Mobitz II
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 Grainger, 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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All sites listed under NCT06305780

Durham, North Carolina, 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_B

Identifier Type: -

Identifier Source: org_study_id

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