Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen

Not Applicable

Completed

• Conditions: High Bleeding Risk; Coronary Artery Disease; PCI
• Interventions: Drug: Aspirin; Drug: P2Y12 inhibitor

• Registration Number: NCT03023020
• Lead Sponsor: ECRI bv

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.

Study Timeline

• Study First Submitted: 2016-12-29
• Study First Submitted QC: 2017-01-13
• Study First Posted: 2017-01-18
• Study Start: 2017-04-04
• Primary Completion: 2021-04-30
• Study Completion: 2021-04-30
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-19
• Last Update Posted: 2021-08-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4579

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Abbreviated antiplatelet regimen	P2Y12 inhibitor	Dual antiplatelet therapy is discontinued immediately after randomization (i.e. 1 month post stent implantation), 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 immediately after randomization (i.e. 1 month post stent implantation), 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)
Prolonged antiplatelet regimen	P2Y12 inhibitor	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). Either aspirin or Clopidogrel is continued up to 11 months post randomization (i.e. 12 months post stent implantation)
Abbreviated antiplatelet regimen	Aspirin	Dual antiplatelet therapy is discontinued immediately after randomization (i.e. 1 month post stent implantation), 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 immediately after randomization (i.e. 1 month post stent implantation), 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)
Prolonged antiplatelet regimen	Aspirin	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). Either aspirin or Clopidogrel is continued up to 11 months post randomization (i.e. 12 months post stent implantation)

Primary Outcome Measures

Name	Time	Method
Major or clinically relevant non-major bleeding (MCB) defined as a composite of type 2, 3 and 5 BARC bleeding events	11 months
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

Secondary Outcome Measures

Name	Time	Method
Urgent non-target vessel revascularization	14 months
Clinically indicated non-target vessel revascularization	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
Urgent target vessel revascularization	14 months
Stroke	14 months
All cause death	14 months
Death from cardiovascular causes	14 months
Myocardial infarction	14 months

Trial Locations

Locations (138)

Buenos Aires Research center; 🇦🇷 Buenos Aires, Argentina

Interventional Cardiology Sanatorio; 🇦🇷 Buenos Aires, Argentina

The Prince Charles Hospital; 🇦🇺 Chermside, Australia

St Vincents Hospital Melbourne; 🇦🇺 Melbourne, Australia

Research Center Perth; 🇦🇺 Perth, Australia

Research Center Sydney; 🇦🇺 Sydney, Australia

Wollongong Research Center; 🇦🇺 Wollongong, Australia

Research Center , 043-02; 🇦🇹 Wien, Austria

Research Center, 043-01; 🇦🇹 Wien, Austria

Research Centre Manama; 🇧🇭 Manama, Bahrain

Scroll for more (128 remaining)