Ivabradine for Long-Term Effects of COVID-19 With POTS Cohort

Eligibility Criteria

• 1. Age 18-80
• 2. History of documented COVID-19 infection of any severity to include a positive COVID-19 PCR, or antibody test
• 3. Meets criteria for 'long-haul' COVID-19 with symptoms \>12 weeks following acute illness
• 4. Able and willing to provide informed consent and participate for study duration
• 5. Willing to participate in the nested randomized controlled trial of ivabradine if RCT enrollment criteria are met
• 6. Access to a primary healthcare provider and proof of health insurance
• 1. Age 18-80
• 2. History of documented COVID-19 infection of any severity to include a positive COVID-19 PCR, or antibody test
• 3. Does not meet criteria for 'long-haul' COVID-19
• 4. Able and willing to provide informed consent and participate for study duration
• 5. Willing to participate in the nested randomized controlled trial of ivabradine if RCT enrollment criteria are met
• 6. Access to a primary healthcare provider and proof of health insurance
• 1. Age 18-80; Meets criteria for 'long-haul' COVID-19
• 1. Documented history of COVID-19 infection made available to study team 1914
• 2. Lack of documented history, but evidence of infection from sensitive antibody tests
• 2. Able and willing to provide informed consent and participate for study duration
• 3. Volunteers with or without LHC combined with POTS based on an increase in comparing the supine heart rate to standing heart rate \>20 beats per minute with a drop in systolic blood pressure less than 20 mm Hg or a drop in diastolic blood pressure less than 10 mm Hg will be included, OR additionally, volunteers with or without LHC and a 24-hour mean heart rate of 90 beats per minute or more (in sinus rhythm) will be diagnosed with IST and be included.
• 4. For females of childbearing age - willing to use a highly effective form of contraceptive with \<1% failure rate or practice abstinence for the duration of the study
• 1. Resting heart rate \<60 bpm
• 2. Atrial fibrillation
• 3. Supraventricular tachycardia
• 4. Allergic reaction or known contraindications to study drug
• 1. Acute decompensated heart failure
• 2. Clinically significant hypotension, defined as a drop in systolic BP \>20 mmHg or drop in diastolic \>10 mmHg during orthostatic vital signs testing.
• 3. Sick sinus syndrome, sinoatrial block or 3rd degree AV block, unless a functioning demand pacemaker is present
• 4. Clinically significant bradycardia
• 5. Severe hepatic impairment
• 6. Pacemaker dependence (heart rate maintained exclusively by the pacemaker)
• 7. Concomitant use of cytochrome P450 3A4 (CYP3A4) inhibitors or inducers
• 5. Pregnant/lactating females
• 6. Impaired gastrointestinal absorption that would preclude oral drug administration
• 7. Taking any of the following without discontinuation in consultation with the volunteer's healthcare provider and a one-week washout period:
• 1. ivabradine
• 2. beta-blockers
• 3. calcium- channel blockers
• 4. cholinesterase inhibitors (pyridostigmine),
• 5. vasoconstrictors (midodrine, octreotide, droxidopa, stimulants)
• 6. sympatholytics (clonidine, methyldopa)
• 7. blood volume enhancers (fludrocortisone, desmopressin, salt supplementation)
• 8. oral ketoconazole (contraindicated)
• 8. Acute suicidality identified at screening