Endpoint selection for noninferiority percutaneous coronary intervention trials: a methodological description

Area of Science:

• Cardiovascular Research
• Medical Device Studies
• Clinical Trial Design

Background:

• Noninferiority (NI) studies are essential for evaluating new percutaneous coronary intervention (PCI) devices.
• Endpoint selection in NI trials significantly impacts study power and interpretation.

Purpose of the Study:

• To provide a practical update on selecting endpoints for NI studies in PCI.
• To explore the current importance of NI designs and intrapatient comparisons.

Main Methods:

• Conducted a PubMed search for relevant terms on NI designs and intrapatient comparisons.
• Performed sample size calculations for common endpoints in NI hypotheses.

Main Results:

• Major adverse cardiac events (MACE) is a frequent endpoint in NI trials, with margins from 1.66% to 5.00%.
• Composite endpoints (MACE + bleeding/stent thrombosis) enhance statistical and clinical meaningfulness.
• Intrapatient randomization with surrogate endpoints can halve patient population requirements.
• Stent thrombosis alone is insufficient as a primary endpoint; combined with MACE/bleeding is feasible.

Conclusions:

• Expanded composite endpoints (MACE + stent thrombosis/bleeding) are suitable for future PCI device approval and reimbursement.
• Intrapatient randomization for surrogate endpoints offers an efficient alternative for specific PCI trials.