Crossover Study of Propranolol vs Ivabradine in POTS

Trial details

Who runs it

University of Calgary

Trial code

NCT04186286

Record updated

9 May 2024

Original description

1.0 BACKGROUND Postural tachycardia syndrome (POTS) is a disorder of chronic orthostatic intolerance characterized by symptoms of palpitations, lightheadedness, chest discomfort, shortness of breath, blurred vision, and mental clouding. These symptoms occur during standing and are associated with a marked increase in heart rate (HR) in the absence of hypotension, which typically resolve when sitting or lying down. Most importantly, POTS is associated with a very poor quality of life and significant functional disability. POTS patients commonly experience mental clouding ("brain fog") even while lying down or seated, which poses significant limitations to daily activities .Read full original descriptionShow less

A Randomized Crossover Study of Propranolol Versus Ivabradine in Postural Tachycardia Syndrome (POTS)

1.0 BACKGROUND Postural tachycardia syndrome (POTS) is a disorder of chronic orthostatic intolerance characterized by symptoms of palpitations, lightheadedness, chest discomfort, shortness of breath, blurred vision, and mental clouding. These symptoms occur during standing and are associated with a marked increase in heart rate (HR) in the absence of hypotension, which typically resolve when sitting or lying down. Most importantly, POTS is associated with a very poor quality of life and significant functional disability. POTS patients commonly experience mental clouding ("brain fog") even while lying down or seated, which poses significant limitations to daily activities .

Unfortunately, there is a relative paucity in the literature assessing therapies for POTS patients. Given that excessive tachycardia on standing is a fundamental component of this syndrome, a handful of studies have evaluated medications that reduce HR. Ivabradine is newer drug that is a selective If channel blocker that reduces HR without affecting other cardiovascular functions.

2.0 RATIONALE / STUDY PURPOSE The investigators propose to compare the efficacy of propranolol and ivabradine on HR response to standing, and symptom burden in patients with POTS.

3.0 Study Design This will be a single-center double-blind placebo-controlled randomized crossover trial conducted in patients with POTS to compare effects of (1) oral ivabradine 5 mg bid plus placebo BID (to fill out a QID schedule); (2) oral propranolol 10 mg qid; and (3) oral placebo qid in POTS patients. After a baseline screening assessment following a washout period of 7 days, participants will be randomized to start with a 4-week course of either ivabradine, propranolol or placebo. The other two treatments will be given in separate 4-week courses with a 7-day washout period between phases, with each participant acting as his or her own control. At the end of each 4-week phase, participants will complete the symptom-rating and HRQOL questionnaires, and also undergo tilt table testing to assess the change in HR at 10 min with head up tilt.

Participants will undergo POTS testing at baseline and at the end of each 4-week treatment course. This will involve a total of 4 separate study visits.

Inclusion: Diagnosis of Postural Tachycardia Syndrome; Age between 18-60 years; Men and women are eligible; Able and willing to provide informed consent.

Exclusion: Known coronary artery disease or prior myocardial infarction; Inability to safely withdraw from existing beta-blockers or ivabradine prior to the study day; Concomitant use of strong cytochrome P450 3A4 (CYP 3A4) inhibitors; Seated resting heart rate < 70 bpm in the absence of rate-lowering medications; Presence of underlying structural heart disease including:; Valvular disease (i.e. moderate or greater valvular stenosis or regurgitation); History of heart failure; Greater than mild left ventricular systolic impairment; History of tachyarrhythmias including:; History of sick sinus syndrome or high degree AV block; Presence of a pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy device; Diabetes mellitus or history of hypoglycemic episodes; History of bronchospasm or uncontrolled asthma; Severe hepatic impairment; Pre-existing long QT interval (e.g. known congenital long QT syndrome, or QT interval >500 ms); Pregnant (by history or serum test) or breast-feeding; Concomitant use of class I and III antiarrhythmic agents, or non-dihydropyridine calcium channel blockers; Supine blood pressure < 90/60 mmHg; Overt cause for postural tachycardia, i.e., acute dehydration, prolonged bed rest; Hypertrophic cardiomyopathy; Supraventricular tachycardia, atrial tachycardia, atrial fibrillation / flutter; Ventricular tachyarrhythmias; Any contraindication to propranolol or ivabradine not specifically listed above as per the product monographs; Unable to give informed consent.

ClinicalTrials.gov NCT04186286