This study is a platform protocol designed to be flexible so that it is suitable for awide range of settings within health care systems and in community settings where it canbe integrated into COVID-19 programs and subsequent treatment plans.This protocol is a prospective, multi-center, multi-arm, randomized, controlled platformtrial evaluating various interventions for use in the treatment of autonomic dysfunctionsymptoms, including cardiovascular complications and postural orthostatic tachycardiasyndrome (POTS), in PASC participants. The interventions tested will includenon-pharmacologic care and pharmacologic therapies with study drugs.
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.
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).
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.
Behavioral: Usual Care
Participants will receive usual non-pharmacologic care (control) for a duration of 3
months, concurrent with ivabradine administration.
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 and
experiencing orthostatic symptoms. Orthostatic tachycardia defined as: Increase of 30
beats per minute (bpm) or more in HR within 10 minutes upon standing without orthostatic
hypotension (decline of ≥ 20 mmHg of systolic or ≥ 10 mmHg of diastolic blood pressure
after 3 minutes of standing) OR History of documented increase of 30 bpm or more from an
active stand test or tilt table test without orthostatic hypotension in the past 1 year
AND standing HR above 100 bpm at the Screening/Baseline visit active stand test.
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 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
3. Combination with verapamil or diltiazem which are moderate CYP3A4 inhibitors with
heart rate reducing properties
4. Severe hepatic impairment
5. Use of drugs known to prolong the QT-interval (e.g., quinidine, disopyramide,
bepridil, sotalol, amiodarone, pimozide, ziprasidone, sertindole, mefloquine,
halofantrine, pentamidineUse of drugs known to prolong the QT-interval (e.g.,
quinidine, disopyramide, bepridil, sotalol, amiodarone, pimozide, ziprasidone,
sertindole, mefloquine, halofantrine, pentamidine
6. Concomitant use of digoxin or Paxlovid
7. Known history of atrial fibrillation or significant cardiac arrhythmia not due to
reversible cause
8. Participants who are pacemaker dependent
9. Patients with hypokalemia (serum K+<3.5 mEq/L)
10. Patients taking potassium-depleting diuretics, unless potassium level is normal at
the baseline CMP, in which case participants may continue taking it during the
study.
11. A history of congenital or acquired long QT syndrome, with or without torsade de
pointes
12. Patients with high degree AV block such as Type 2 AV block, Mobitz II
All sites listed under NCT06305780
Durham, North Carolina, United States