High Bleeding Risk, Coronary Artery Disease, PCI
Conditions
Keywords
Dual Antiplatelet Therapy
Brief summary
The study compares two lengths of medication therapy (a shortened versus a prolonged dual antiplatelet therapy) in order to prevent thrombus (blood cloth) formation after the successfully treatment for coronary heart disease with a drug covered stent (metallic tube). This comparison will be done in patients who, compared to the average patient, are more likely to suffer from complications on antiplatelet therapy (bleeding). Both durations are within the current medical recommendations. The aim of this study is to help improve further standard antiplatelet duration guidelines.
Detailed description
The study objective is to determine in a high bleeding risk patient population undergoing PCI under standardized treatment (within current guidelines and instructions for use and including the bioresorbable polymer coated Ultimaster sirolimus-eluting stent), whether abbreviated DAPT is non-inferior to prolonged DAPT regimen in terms of NACE within 12 months, whether abbreviated DAPT is non-inferior to prolonged DAPT regimen in terms of MACCE within 12 months and whether abbreviated DAPT is superior to prolonged DAPT regimen in terms of MCB within 12 months. There are two treatment strategies: * abbreviated dual anti-platelet therapy: dual antiplatelet therapy is discontinued and a single antiplatelet agent is continued until at least 11 months post randomization (i.e. 12 months post stent implantation). In patients on oral anticoagulants, dual antiplatelet therapy is discontinued and either Aspirin or Clopidogrel is continued until 5 months post randomization (i.e. 6 months post stent implantation). Oral anticoagulation is continued until at least 11 months post randomization (i.e. 12 months post stent implantation) OR * prolonged dual anti-platelet therapy: aspirin is continued for at least 11 months post randomization (i.e. 12 months post stent implantation), the P2Y12 inhibitor being taken at the time of randomization is continued for at least 5 months and up to 11 months post randomization (i.e. 12 months post stent implantation). In patients on oral anticoagulants, aspirin and Clopidogrel are continued for at least 2 months post randomization (i.e. 3 months post stent implantation) and up to 11 months post randomization (i.e. 12 months after stent implantation). Therefore either aspirin or Clopidogrel is continued up to 11 months post randomization (i.e. 12 months post stent implantation) The study design is an investigator-initiated, randomized, multi-center, clinical trial to be conducted in approximately 100 interventional cardiology centers in across the globe excluding USA. The study includes 2 x 2150 patients (i.e. 4300 patients) Randomization will occur at one month after the PCI procedure. The expected duration of participation for each patient is 14 months.
Interventions
DRUGAspirin
Dosing per current guidelines and local practice
DRUGP2Y12 inhibitor
Dosing per current guidelines and local practice
Sponsors
Cardialysis B.V.
European Cardiovascular Research Center
University of Bern
Terumo Medical Corporation
ECRI bv
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
After index PCI, patients aged 18 years or more are eligible for inclusion into the study if the following criteria are met. 1. At least one among the HBR criteria (as defined below) is met. 2. All lesions are successfully treated with Ultimaster stent in the context of routine clinical care, i.e. post-procedural angiographic diameter stenosis \<20% by visual estimation 3. Free from any flow-limiting angiographic complications (i.e. significant untreated dissection or major side-branch occlusion), which require prolonged DAPT duration based on operator's opinion. 4. All stages of PCI are complete (if any) and no further PCI is planned. At randomization visit (one month after index PCI), the following criteria must be met: 1. Fulfilment of at least one HBR criterion (as defined below), or on the basis of post-PCI actionable (i.e. requiring medical attention) non-access site related bleeding episode 2. Uneventful 30-day clinical course, i.e. free from spontaneous MI, symptomatic restenosis, stent thrombosis, stroke and any revascularization (coronary and non-coronary) requiring prolonged DAPT 3. If not on OAC, 1. Patient is on a DAPT regimen of aspirin and a P2Y12 inhibitor 2. Patient with one type of P2Y12 inhibitor for at least 7 days (i.e. no switching between oral P2Y12 inhibitors has occurred in the previous 7 days) 4. If on OAC 1. Patient is on the same type of OAC (e.g. Vitamin K antagonist or NOAC) for at least 7 days 2. Patient is on clopidogrel for at least 7 days Definition of HBR Post-PCI patients are at HBR if at least one of the following criteria applies: * Clinical indication for treatment with oral anticoagulants (OAC) for at least 12 months * Recent (\<12 months) non-access site bleeding episode(s), which required medical attention (i.e. actionable bleeding). * Previous bleeding episode(s) which required hospitalization if the underlying cause has not been definitively treated (i.e. surgical removal of the bleeding source) * Age equal or greater than 75 years * Systemic conditions associated with an increased bleeding risk (e.g. haematological disorders, including a history of or current thrombocytopaenia defined as a platelet count \<100,000/mm3 (\<100 x 109/L), or any known coagulation disorder associated with increased bleeding risk. * Documented anaemia defined as repeated haemoglobin levels \<11 g/dl or transfusion within 4 weeks before randomization. * Need for chronic treatment with steroids or non-steroidal anti-inflammatory drugs * Diagnosed malignancy (other than skin) considered at high bleeding risk including gastro-intestinal, genito-urethral/renal and pulmonary. * Stroke at any time or TIA in the previous 6 months * PRECISE DAPT score of 25 or greater
Exclusion criteria
1. Treated with stents other than Ultimaster stent within 6 months prior to index procedure 2. Treated for in-stent restenosis or stent thrombosis at index PCI or within 6 months before 3. Treated with a bioresorbable scaffold at any time prior to index procedure 4. Cannot provide written informed consent 5. Under judicial protection, tutorship or curatorship 6. Unable to understand and follow study-related instructions or unable to comply with study protocol 7. Active bleeding requiring medical attention (BARC≥2) on randomization visit 8. Life expectancy less than one year 9. Known hypersensitivity or allergy for aspirin, clopidogrel, ticagrelor, prasugrel, cobalt chromium or sirolimus 10. Any planned and anticipated PCI 11. Participation in another trial 12. Pregnant or breast feeding women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Net adverse clinical endpoints (NACE) defined as a composite of all-cause death, myocardial infarction, stroke and bleeding events defined as BARC 3 or 5 | 11 months |
| Major adverse cardiac and cerebral events (MACCE) defined as a composite of all-cause death, myocardial infarction and stroke | 11 months |
| Major or clinically relevant non-major bleeding (MCB) defined as a composite of type 2, 3 and 5 BARC bleeding events | 11 months |
Secondary
| Measure | Time frame |
|---|---|
| Clinically indicated non-target vessel revascularization | 14 months |
| All cause death | 14 months |
| Death from cardiovascular causes | 14 months |
| Myocardial infarction | 14 months |
| Transfusion rates both in patients with and/or without clinically detected over bleeding | 14 months |
| Bleeding events | 14 months |
| Definite or probable stent thrombosis | 14 months |
| Any target vessel revascularization | 14 months |
| Stroke | 14 months |
| Urgent target vessel revascularization | 14 months |
| Urgent non-target vessel revascularization | 14 months |
Countries
Argentina, Australia, Austria, Bahrain, Bangladesh, Belgium, Bulgaria, Czechia, Denmark, Estonia, France, Germany, Hungary, India, Israel, Italy, Japan, Netherlands, North Macedonia, Poland, Saudi Arabia, Serbia, Singapore, Slovenia, South Korea, Spain, Sweden, Switzerland, United Kingdom, Vietnam
Outcome results
None listed