Routine versus selective protamine administration to reduce bleeding after TAVI: Rationale and design of the POPular ACE TAVI trial.

BACKGROUND

Unfractionated heparin is routinely used during transcatheter aortic valve implantation (TAVI) to reduce catheter thrombosis and thromboembolism. Protamine reverses the effect of heparin and may lower bleeding risk, but it can also trigger severe allergic reactions. Robust data on the safety and efficacy of routine protamine administration after TAVI is lacking.

METHODS

The ``routine versus selective protamine administration to reduce bleeding complications after transcatheter aortic valve implantation (POPular ACE TAVI)'' is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized clinical trial. A total of 1000 patients will be randomized 1:1 to routine versus selective protamine administration, stratified by study site and antithrombotic therapy. Primary and secondary outcomes are defined according to the Valve Academic Research Consortium-3 (VARC-3) criteria. The primary outcome is a composite of all-cause mortality and clinically relevant bleeding (type 1-4) within 30 days after TAVI. Ranked secondary outcomes include clinically relevant bleeding; major, life-threatening or fatal bleeding (type 2-4); major vascular complications; cardiovascular mortality; and all-cause mortality. Safety outcomes include anaphylaxis and thromboembolic events defined as the composite of myocardial infarction, ischemic stroke, transient ischemic attack, or noncerebral distal embolization. Recruitment began in November 2023 and will continue until 1,000 patients are randomized. The trial will end after 30‑day follow‑up of the last patient.

CONCLUSION

The POPular ACE TAVI trial (NCT05774691) will evaluate whether routine protamine administration reduces all-cause mortality or clinically relevant bleeding after TAVI compared with selective use.

TRIAL REGISTRATION: clinicaltrials.gov. Unique identifier NCT05774691.