Clinical trial

RECOVER-AUTONOMIC (Ivabradine): Randomized Trial of the Effect of Ivabradine Versus Placebo on Long COVID Symptoms

Name

Pro00112597_B

Description

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.

Trial arms

Trial start

2024-03-11

Estimated PCD

2025-12-01

Trial end

2026-03-01

Phase

Early phase I

Treatment

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).

Arms:

Ivabradine + Coordinated Care, Ivabradine + Usual Care

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).

Arms:

Ivabradine Placebo + Coordinated Care, Ivabradine Placebo + Usual Care

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.

Arms:

Ivabradine + Coordinated Care, Ivabradine Placebo + Coordinated Care

Usual Care

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

Arms:

Ivabradine + Usual Care, Ivabradine Placebo + Usual Care

Size

180

Primary endpoint

Change in Orthostatic Hypotension Questionnaire (OHQ)/Orthostatic Intolerance Questionnaire (OIQ) Composite Score

Baseline to End of Intervention (3 months)

Eligibility criteria

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: 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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'TRIPLE', 'maskingDescription': 'Double blind', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 180, 'type': 'ESTIMATED'}}

Updated at

2024-04-09

1 organization

1 product

3 indications

Organization

Kanecia Obie Zimmerman

Product

Indication

Indication

Indication