CD2H COVID-19

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

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

Long COVID
Long Covid19
Long Covid-19

Eligibility

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

Inclusion Criteria

See NCT06305780 for RECOVER-AUTO: Platform Protocol level inclusion criteria which applies to this appendix (or sub-study) Additional Appendix B (Ivabradine Sub-study) Level 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: - See NCT06305780 for RECOVER-AUTO: Platform Protocol level inclusion criteria which applies to this appendix (or sub-study) Additional Appendix B (Ivabradine Sub-study) Level

Exclusion Criteria

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

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

Arm	Description	Assigned Intervention
Experimental 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	Drug: 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). Behavioral: 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.
Experimental Ivabradine Placebo + Coordinated Care		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). Behavioral: 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.
Experimental 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	Drug: 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). Behavioral: Usual Care Participants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with ivabradine administration.
Experimental Ivabradine Placebo + Usual Care		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). Behavioral: Usual Care Participants will receive usual non-pharmacologic care (control) for a duration of 3 months, concurrent with ivabradine administration.

Recruiting Locations

More Details

NCT ID: NCT06305806
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.