Clinical trial NCT05066789: CHoice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 4
Official title: Comparison of Polymer-Free Cobalt-Chromium Thin Drug-Coated Stents With Biodegradable Polymer Ultrathin Sirolimus-Eluting Stents and Prasugrel Monotherapy With Conventional 12-Month Dual Antiplatelet Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: Percutaneous Coronary Intervention
Acute coronary syndrome
Antiplatelet Therapy
Drug eluting stent
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2021-10-04
Enrollment: 100
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: multi-center, open label, two-by-two factorial, randomized, noninferiority trial
Primary purpose: TREATMENT

Brief summary: This study is multi-center, open label, two-by-two factorial, randomized, noninferiority trial to compare the efficacy and safety of polymer-free cobalt-chromium thin drug-coated stents (BioFreedom Ultra) with biodegradable polymer ultrathin sirolimus-eluting stents (Orsiro Mission) and prasugrel monotherapy after 1-month dual antiplatelet therapy (DAPT) of aspirin plus prasugrel with 12-month DAPT of aspirin plus prasugrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Detailed description: Polymer is the key component of drug-eluting stents (DES) for facilitation of drug loading and control of drug release. However, durable polymer of the 1st generation DES has been considered to induce inflammation and to be associated with fatal complications such as very late stent thrombosis. To overcome this shortcoming, biodegradable polymer has been applied to the DES system. In several head-to-head comparison, ultrathin strut biodegradable polymer sirolimus-eluting Orsiro stent demonstrated comparable or superior outcomes compared with durable polymer everolimus-eluting stents. As a result, Orsiro stent is considered one of the standard contemporary DESs.

On the other hand, polymer-free drug-coated stents (DCS) have been developed as an alternative to durable and biodegradable polymer DES. The biolimus A9-coated BioFreedom stent is the representative polymer-free drug-coated stent and was superior to a bare-metal stent in patients treated with 1-month dual antiplatelet therapy (DAPT). However, it failed to show noninferiority for major adverse cardiovascular events at 12 months when compared with the ultrathin strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population, mainly due to increased target lesion revascularization (TLR). On top of possible insufficient or uncontrolled drug delivery at stented site due to absence of a drug carrier, thick strut (112 µm) and stainless steel alloy may explain a higher rate of TLR in the BioFreedom stent group compared with the Orsiro stent group. The BioFreedom Ultra stent is a novel cobalt-chromium thin stent (84 µm) with biolimus A9-coating. With advancement in stent alloy and strut thickness, treatment efficacy and safety of the BioFreedom Ultra stent would be comparable to the new version of Orsiro stent (Orsiro Mission) among patients with acute coronary syndrome (ACS).

Patients with ACS undergoing percutaneous coronary intervention (PCI) with DES are currently recommended to use 12 months of DAPT, consisting of aspirin and P2Y12 inhibitor. Although use of DAPT reduces ischemic events, including stent thrombosis, bleeding events increase in return. Hence, considering the aforementioned advancement of stent devices, shorter duration of DAPT and switching to a potent P2Y12 inhibitor monotherapy would be possible. This has been demonstrated in several recent studies. However, although prasugrel was superior to ticagrelor in lowering ischemic events, these studies mainly used ticagrelor as a solely used antiplatelet agent, and studies verifying the effect of prasugrel monotherapy after short duration of DAPT are limited to date. In addition, in these studies, DAPT was maintained for mostly at least 3 months in the ACS situation. With advancement of devices, duration of DAPT may be further reduced. In other words, prasugrel monotherapy after 1 month of DAPT of aspirin plus prasugrel would be comparable to 12-month DAPT of aspirin plus prasugrel.

Eligibility criteria: Inclusion Criteria:

1. Subject must be at least 19 years of age
2. Subject who is able to understand risks, benefits and treatment alternatives and sign informed consent voluntarily.
3. Patients presenting with ACS (ST-elevation myocardial infarction \[STEMI\], non-ST-elevation myocardial infarction \[NSTEMI\], or unstable angina)
4. Patients with at least one lesion with equal or greater than 50% diameter stenosis requiring treatment with drug-eluting stents (DES) in native coronary artery or graft

Exclusion Criteria:

1. Patients unable to provide consent
2. Patients with known intolerance to aspirin, clopidogrel, prasugrel, or major components of drug-eluting stents
3. Patients who have non-cardiac co-morbid conditions with life expectancy \<1 year or that may result in protocol non-compliance (per site investigator's medical judgment)
4. Patients who need chronic anti-coagulation therapy
5. Patients with active pathological bleeding
6. Pregnant or lactating women

Additional Exclusion Criteria for Antiplatelet Comparison Study:

1. Patients with history of stroke or transient ischemic attack
2. Patients 75 years of age or older
3. Patients weighing less than 60 kg

Primary outcomes:
measure: Stent Comparison Study: target-lesion failure (TLF)
timeFrame: 1 year
measure: Antiplatelet Comparison Study: net adverse clinical events (NACE)
timeFrame: 1 year
Secondary outcomes:
measure: Stent Comparison Study: TLF
timeFrame: 3 years
measure: Stent Comparison Study: target-vessel failure
timeFrame: 1 and 3 years
measure: Stent Comparison Study: cardiac death
timeFrame: 1 and 3 years
measure: Stent Comparison Study: target-vessel myocardial infarction (MI)
timeFrame: 1 and 3 years
measure: Stent Comparison Study: clinically indicated TLR
timeFrame: 1 and 3 years
measure: Stent Comparison Study: stent thrombosis
timeFrame: 1 and 3 years
measure: Stent Comparison Study: clinically indicated target-vessel revascularization (TVR)
timeFrame: 1 and 3 years
measure: Stent Comparison Study: cardiac death or MI
timeFrame: 1 and 3 years
measure: Stent Comparison Study: cardiac death, MI, or stent thrombosis
timeFrame: 1 and 3 years
measure: Stent Comparison Study: all-cause death
timeFrame: 1 and 3 years
measure: Stent Comparison Study: MI
timeFrame: 1 and 3 years
measure: Stent Comparison Study: all-cause death or MI
timeFrame: 1 and 3 years
measure: Stent Comparison Study: any revascularization
timeFrame: 1 and 3 years
measure: Stent Comparison Study: restricted mean survival time for the TLF
timeFrame: 1 and 3 years
measure: Antiplatelet Comparison Study: MACCE
timeFrame: 1 year
measure: Antiplatelet Comparison Study: clinically relevant bleeding
timeFrame: 1 year
measure: Antiplatelet Comparison Study: all-cause death
timeFrame: 1 year
measure: Antiplatelet Comparison Study: MI
timeFrame: 1 year
measure: Antiplatelet Comparison Study: stroke
timeFrame: 1 year
measure: Antiplatelet Comparison Study: cardiac death
timeFrame: 1 year
measure: Antiplatelet Comparison Study: stent thrombosis
timeFrame: 1 year
measure: Antiplatelet Comparison Study: all-cause death or MI
timeFrame: 1 year
measure: Antiplatelet Comparison Study: cardiac death or MI
timeFrame: 1 year
measure: Antiplatelet Comparison Study: cardiac death, MI, or stent thrombosis
timeFrame: 1 year
measure: Antiplatelet Comparison Study: BARC type 3 or 5 bleeding
timeFrame: 1 year
measure: Antiplatelet Comparison Study: restricted mean survival time for the NACE
timeFrame: 1 year
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Samsung Medical Center
name: Joo-Yong Hahn, MD, PhD
role: STUDY_CHAIR
References: