A drug company proposes to introduce a new antihypertensive agent that is aimed at elderly hypertensive participants with prior heart disease. Because this is a high-risk group, the company is hesitant to withhold antihypertensive therapy from these patients and instead proposes an equivalence study comparing the new agent (drug A) with the current antihypertensive therapy used by those participants. Hence the participants are randomized to either maintenance of their current therapy or replacement of their current therapy with drug A. Suppose the endpoint is total cardiovascular disease (CVD) mortality, and it is assumed that under their current therapy 15% of participants will die of CVD over the next 5 years.

Suppose drug A will be considered equivalent to the current therapy if the 5-year CVD mortality is not worse than 20%. How many participants must be enrolled in the study to ensure at least an 80% chance of demonstrating equivalence if equivalence will be based on a one-sided 95% CI approach, an equal number of subjects are randomized to drug A and current therapy, and the underlying mortality rates of the two therapies are the same?