Single versus dual antiplatelet therapy after drug-coated balloon angioplasty in elderly or high-bleeding-risk patients

International, Multicenter, Investigator-driven Randomized Clinical Trial to Assess the Single vs. Dual Antiplatelet Therapy in Elderly or HBR Patients Undergoing Percutaneous Intervention With Drug-coated Balloons (PICCOLETO IV-EPIC 38)

This study tests whether taking one antiplatelet medicine is as safe and causes less bleeding than taking two medicines for people aged 75 or older, or adults at high bleeding risk, after drug-coated balloon angioplasty for coronary artery disease.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 576 (estimated)
• Sex: All
• Sponsor: Fondazione Ricerca e Innovazione Cardiovascolare ETS (Academic / other)
• Drugs / interventions: methotrexate
• Locations: 1 site (Milan, MI)
• Trial ID: NCT06535568 on ClinicalTrials.gov

What this trial studies

PICCOLETO IV-EPIC 38 is an international, multicenter, open-label randomized trial that compares single antiplatelet therapy (SAPT) with routine dual antiplatelet therapy (DAPT) after successful percutaneous coronary intervention using the Essential Pro drug-coated balloon in native coronary arteries 2.0–4.0 mm in diameter. Eligible patients are aged 75 years or older or adults classified as high bleeding risk and may have stable or unstable coronary syndromes. Participants are randomized after successful DCB angioplasty and followed for rates of ischemic events and bleeding complications. The trial aims to determine whether SAPT can provide comparable ischemic protection with a lower bleeding burden compared with DAPT in this vulnerable population.

Who should consider this trial

Good fit: Ideal candidates are adults aged ≥75 years or adults at high bleeding risk who have just had a successful PCI with the Essential Pro drug-coated balloon in 1–3 native coronary vessels sized 2.0–4.0 mm and have provided informed consent.

Not a fit: Patients who required stent implantation during the index procedure, have recent stent placement within six months, or have contraindications to aspirin, clopidogrel, paclitaxel, or contrast are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, the approach could give similar protection from heart-related clots while reducing bleeding risk and simplifying medication for elderly or high-bleeding-risk patients.

How similar studies have performed: Related approaches of shorter or single antiplatelet regimens in high-bleeding-risk PCI populations have shown promise, but data specifically after modern drug-coated balloons remain limited.

Eligibility criteria

Inclusion Criteria:

Male and female patients who meet the following criteria:

* Age ≥ 75 years or age ≥ 18 years at high bleeding risk;
* Successful PCI with Essential Pro DCB just performed, in 1, 2 or 3 coronary vessels;
* Stable or unstable coronary syndromes;
* De novo coronary lesions in vessels with diameter ≥2.0 and ≤4.0 mm (visual estimation);
* Informed consent to participate in the study given by the patient or impartial witness.

Exclusion Criteria:

* Stent implantation during index or recent (\<6 months) procedure;
* Known (and untreatable) hypersensitivity or contraindication to aspirin, heparin, clopidogrel, paclitaxel or contrast media, or any of their excipient which cannot be adequately pre-medicated;
* Pregnancy at the time of hospitalization;
* Patients participating in another clinical study in which an investigational drug or device was administered within 30 days of screening or within the 5 half-lives of the study drug, whichever is longer;
* ST-elevation myocardial infarction;
* Life expectancy \<12 months;
* Left ventricular ejection fraction \<30%;
* Visible thrombus at lesion site;
* Target lesion/vessel with any of the following characteristics:

  * severe and/or \>270° calcification of the target vessel, also proximal to the lesion (intravascular imaging not mandatory);
  * left main stem stenosis \>50%;
  * target lesion is in the left main stem;
  * chronic total occlusion with anticipated necessity of retrograde approach;
  * lesion is in a bypass graft.
* History of asthma induced by the administration of salicylates or substances with a similar action, notably non-steroidal anti-inflammatory medicines (NSAIDs);
* History of gastrointestinal perforation, ulceration, or bleeding (peptic ulcer bleeding-PUBs) related to previous use of NSAIDs or anticoagulant medications, or intracranial hemorrhage;
* Acute gastrointestinal ulcers;
* Hemorrhagic diathesis (including known bleeding disorders or ongoing active bleeding);
* Severe renal impairment (eGFR \< 30 mL/min);
* Severe hepatic impairment (Child-Pugh C), with elevated liver enzymes (ALT/AST \> 2 x ULN or total bilirubin \>1.5 x ULN);
* Severe cardiac failure (NYHA grade III or IV);
* Combination with methotrexate at doses of 15 mg/week or more;
* Patients with baseline neutrophil counts \< 1500 cells/mm³;
* Breastfeeding women;
* Full-blown thyrotoxicosis;
* Patients with a very high risk of thrombosis.

Where this trial is running

Milan, MI

• IRCCS Auxologico Milano — Milan, Mi, Italy (Recruiting)

Study contacts

• Study coordinator: Bernardo Cortese, MD MSc

Conditions Coronary Disease; Heart Diseases; Cardiovascular Diseases; Myocardial Ischemia; Atherosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Coronary Artery Disease