Fondazione Ricerca e Innovazione Cardiovascolare and Fundación EPIC Launch PICCOLETO IV-EPIC Clinical Trial

Italian-Spanish collaboration advances interventional cardiology research through landmark multicenter study

Milan, Italy — Fondazione Ricerca e Innovazione Cardiovascolare ETS (Fondazione RIC), a leading independent non-profit research foundation at the forefront of cardiovascular innovation, in collaboration with Fundación EPIC (Educación en Procedimientos de Intervencionismo en Cardiología), Spain's premier foundation dedicated to excellence in interventional cardiology education and research, proudly announces the official launch of the PICCOLETO IV clinical trial at Auxologico Research Hospital, Milan, Italy.

PICCOLETO IV is an international multicenter, investigator-driven, open-label, randomized (1:1), clinical investigation designed to observe and evaluate the rate of ischemic and bleeding adverse events of a single antiplatelet regimen (SAPT) since the time of PCI with latest generation DCB in elderly or high bleeding risk population with stable or unstable coronary syndromes. The study will enroll approximately 576 patients across 20 centers in 4 countries (Spain, Italy, Belgium, and Luxembourg), with a planned follow-up period of 12 months.

As per international guidelines, coronary lesions are primarily treated with drug-eluting stents (DES). While DES have demonstrated good clinical outcomes, even the latest generations remain associated with restenosis, vessel thrombosis, and myocardial infarction. In addition, DES carry an intrinsic thrombotic risk, requiring dual antiplatelet therapy (DAPT). However, elderly patients and those at higher bleeding risk (HBR) have a cumulative increase in adverse events, including a higher thrombotic risk after angioplasty with DES.

Recently drug-coated balloons (DCB) have emerged as an attractive alternative for the treatment of coronary de-novo lesions. In the most recent years, a new generation of DCB have been developed, with the aim of improving the trackability and deliverability of these devices, along with an improvement of drug release and persistence in the vessel wall. 

The PICCOLETO IV study evaluates a DCB strategy in native coronary artery disease using the Essential Pro DCB, followed by single antiplatelet therapy (SAPT) instead of DAPT. The study addresses whether SAPT after successful DCB angioplasty is safe and effective compared with standard DAPT in patients aged ≥75 years or those identified as high bleeding risk (HBR) with either stable or unstable coronary syndromes.

Leadership Perspectives

"This study is very important, because it will find the right spot for DCB in a very high risk patient population, namely elderly patients or patients at high bleeding risk. Stents do not perform well here, either for the necessity of a prolonged double antiplatelets duration, and for a higher pro-thrombotic risk. With this scientifically robust randomized clinical trial we will deeply investigate the role of DCB here."

— Prof. Bernardo Cortese, Fondazione RIC

"After the publication of the DCB ARC consensus papers in 2025, the time to explore additional indications for DCB has come."

— Dr. Armando Perez de Prado, Fundación EPIC

About Fondazione Ricerca e Innovazione Cardiovascolare ETS

Fondazione Ricerca e Innovazione Cardiovascolare ETS (Fondazione RIC) is a leading independent non-profit research foundation dedicated to advancing cardiovascular science and improving patient outcomes. Uniquely positioned as the only research entity worldwide with deep, dedicated expertise in Drug-Coated Balloon (DCB) technologies, the Foundation has executed over 15 clinical trials, enrolled more than 6,000 patients, and engaged a multinational network of approximately 300 clinical centers across 20 countries.

By leveraging its independent non-profit status, Fondazione RIC delivers unbiased, academically credible research results that increase trust among regulators, payers, and the scientific community. The Foundation ensures scientific visibility through dissemination at leading international congresses (EuroPCR, ESC, TCT, CRT) and peer-reviewed publications coordinated with global Key Opinion Leaders.

Through a strict collaboration with DCB Academy, Fondazione RIC also constitutes a leading educational institution for cardiologists from all around the globe.

For more information: www.fondazioneric.org

About Fundación EPIC

Fundación EPIC (Educación en Procedimientos de Intervencionismo en Cardiología) is a Spanish non-profit foundation committed to fostering excellence in the treatment of cardiovascular diseases through percutaneous transcatheter techniques. Based in León, Spain, the Foundation serves as a hub for education, training, research, and innovation in the field of interventional cardiology.

For more information: www.fundacionepic.org

Media Contacts

Fondazione Ricerca e Innovazione Cardiovascolare ETS

Email: clinicaltrials@fondazioneric.org

Website: www.fondazioneric.org

Address: Via Ettore Ponti 49, Milano, Italy