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

Inclusion 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

Inclusion Criteria for non-LHC Cohort

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

Inclusion Criteria for POTS RCT:

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

Exclusion Criteria:

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

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