Prevention of Syncope Trial (POST): a randomized clinical trial of beta blockers in the prevention of vasovagal syncope Rationale and study design

BACKGROUND: Few therapies for vasovagal syncope have been proven effective. A large, placebo-controlled clinical trial of beta-blockers is needed. STRUCTURE OF STUDY: The Prevention of Syncope Trial (POST) is a multicentre, randomized, placebo-controlled, study of metoprolol in the prevention of vasovagal syncope. The primary hypothesis is that beta-blockers will increase the time to the first recurrence of syncope when compared with placebo. Patients will be randomized 1:1 to receive metoprolol or placebo, and followed for 1 year. The primary endpoint is the time to first syncope recurrence, and secondary endpoints include syncope frequency, presyncope, and quality of life. INCLUSION AND EXCLUSION CRITERIA: Patients are eligible if they have a positive tilt test and 3 syncopal spells preceding the tilt test. They are excluded if they have seizures or other causes of syncope; important heart disease; a contraindication to or need for beta blockers; a permanent pacemaker; a major noncardiovascular disease; or previous use of beta blockers at a dose greater than the equivalent of metoprolol 25mg twice daily for the purpose of suppressing vasovagal syncope. POWER CALCULATIONS: We assume a 40% risk of syncope in the control arm, an absolute reduction of 20% by metoprolol, and a dropout of 20%. Entry of 220 patients will result in an 80% chance of reaching a positive conclusion about beta-blocker therapy with 2p=0.05.