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

Inclusion Criteria:

• See NCT06305780 for RECOVER-AUTO: Platform Protocol level inclusion criteria whichapplies 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 (anincrease of 30 beats per minute (bpm) or more in HR within 10 minutes upon standingwithout 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 whichapplies 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 serotoninand 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 participantis on a stable dose (>4 weeks). Participants on stable doses will be allowed tocontinue the medication throughout the study.

4. Combination with verapamil or diltiazem which are moderate CYP3A4 inhibitors withheart 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 depointes

13. Patients with high degree AV block such as Mobitz II