The Dual Antiplatelet Therapy Study (DAPT Study)

Study Overview
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Brief Summary
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The DAPT Study is a double blind randomized controlled trial intended to determine the appropriate duration for dual antiplatelet therapy (the combination of aspirin and a second anti-clotting medication) as well as the safety and effectiveness of dual antiplatelet therapy to protect patients from stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE) following the implantation of drug-eluting coronary stents. Similar analysis will be conducted in a smaller cohort of bare metal coronary stent - treated subjects.

Detailed Description
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Subjects with ischemic heart disease due to stenotic lesions in either native coronary arteries or coronary artery bypass grafts undergoing percutaneous coronary intervention (PCI) with stent placement and no contraindications to prolonged dual antiplatelet therapy are eligible to be enrolled in the study. All enrolled subjects will undergo PCI with stent placement. All enrolled subjects will be treated with either an FDA-approved drug eluting stent(s) (DES) or an FDA-approved bare metal stent(s) (BMS) (per their respective Instructions for Use) and assigned to 12 months of open label FDA-approved thienopyridine treatment in addition to aspirin. Operators will select the thienopyridine according to the package insert. Thienopyridine treatment dose will be according to the standard of practice and prescribing information for the selected medication. Aspirin treatment will be 75-325 mg for the first 6 months after the procedure and 75-162 mg subsequently, to be continued indefinitely. All DES or BMS subjects who are treated with 12 months of dual antiplatelet therapy post index procedure and who are event free per protocol will be eligible for randomization to either placebo (12 m DAPT Study arm) or an additional 18 months of thienopyridine treatment (30 m DAPT Study arm). Both arms will continue aspirin therapy. Up to four (4) separate post-market approval studies will be allowed to incorporate the randomized design of the DAPT Study for a subset of subjects who may then be contributed for the DAPT Study analyses.

Official Title
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A Prospective, Multi-center, Randomized, Double-blind Trial to Assess the Effectiveness and Safety of 12 Versus 30 Months of Dual Antiplatelet Therapy in Subjects Undergoing Percutaneous Coronary Intervention With Either Drug-eluting Stent or Bare Metal Stent Placement for the Treatment of Coronary Artery Lesions

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Placebo & Aspirin
* Drug: Clopidogrel & Aspirin, Prasugrel & Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Enrollment): Subject is > 18 years of age. Subjects undergoing percutaneous intervention with stent deployment (or has w/in 24 hours). Subjects without known contraindication to dual antiplatelet therapy for at least 30 months after enrollment and stent implantation. The subject has consented to participate and has authorized the collection and release of his medical information by signing the Patient Informed Consent Form. The informed consent will be valid for the duration of the trial or until the subject withdraws. Inclusion Criterion (Randomization at 12 months): 1. Subject, at 12 months, is free from death, MI, stroke, repeat coronary revascularization, major bleeding, and stent thrombosis and has been compliant with dual antiplatelet therapy following stent implantation. Exclusion Criteria (Enrollment): Index procedure stent placement with stent diameter <2.25 mm or >4.0 mm. Pregnant women. Planned surgery necessitating discontinuation of antiplatelet therapy within the 30 months following enrollment. Current medical condition with a life expectancy of less than 3 years. Concurrent enrollment in another device or drug study whose protocol specifically excludes concurrent enrollment or that involves blinded placement of a DES or BMS other than those included as DAPT Study devices. The subject may only be enrolled in the DAPT Study once. Subjects on warfarin or similar anticoagulant therapy. Subjects with hypersensitivity or allergies to one of the drugs or components indicated in the Instructions for Use for the device implanted. Subjects unable to give informed consent. Subject treated with both DES and BMS during the index procedure. Exclusion Criteria (Randomization at 12 months): Pregnant women. Subject switched thienopyridine type or dose within 6 months prior to randomization. Percutaneous coronary intervention or cardiac surgery between 6 weeks post index procedure and randomization. Planned surgery necessitating discontinuation of antiplatelet therapy within the 21 months following randomization. Current medical condition with a life expectancy of less than 3 years. Subjects on warfarin or similar anticoagulant therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 12m DAPT Study Arm<br>This population consists of subjects enrolled in the study who are free from death, MI, stroke, repeat coronary revascularization, major bleeding, and ST 12 months after stent implantation and who are compliant with 12 months of dual antiplatelet therapy following stent implantation and who are subsequently randomized to receive 18 months of placebo treatment in addition to aspirin. | Drug: Placebo & Aspirin<br> <br> |
| Active Comparator: 30m DAPT Study Arm<br>This population consists of subjects enrolled in the study who are free from death, MI, stroke, repeat coronary revascularization, major bleeding, and ST 12 months after stent implantation and who are compliant with 12 months of dual antiplatelet therapy following stent implantation and who are subsequently randomized to receive an additional 18 months of thienopyridine treatment in addition to aspirin. | Drug: Clopidogrel & Aspirin, Prasugrel & Aspirin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACCE (Death, Myocardial Infarction or Stroke) - Randomized DES ITT | The coprimary efficacy endpoints were the cumulative incidence of MACCE and the cumulative incidence of ARC definite or probable stent thrombosis within randomized DES ITT patients between 12 and 30 months post procedure. | 18 months (12-30 months post-index procedure) | 
| Definite or Probable Stent Thrombosis (ST) - Randomized DES ITT | The coprimary efficacy endpoints were the cumulative incidence of MACCE and the cumulative incidence of definite or probable ST within randomized DES ITT patients between 12 and 30 months post procedure. ST was assessed according to the Academic Research Consortium (ARC) definitions. | 18 months (12-30 months post-index procedure) | 
| GUSTO Severe or Moderate Bleeding - Randomized DES ITT | The primary safety endpoint was moderate or severe bleeding within randomized DES ITT patients between 12 and 30 months post procedure. Bleeding was assessed according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) criteria. | 18 months (12-30 months post-index procedure) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACCE (Death, Myocardial Infarction or Stroke) - Propensity Matched DES vs. BMS | Secondary powered endpoint | 33 months (0-33 months post-index procedure) | 
| Definite or Probable Stent Thrombosis (ST) - Propensity Matched DES vs. BMS | Secondary powered endpoint | 33 months (0-33 months post-index procedure) | 
| MACCE (Death, Myocardial Infarction or Stroke) - Randomized DES ITT |  | 21 months (12-33 months post-index procedure) | 
| Definite or Probable Stent Thrombosis (ST) - Randomized DES ITT | ST was assessed according to the Academic Research Consortium (ARC) definitions. | 21 months (12-33 months post-index procedure) | 
| GUSTO Severe or Moderate Bleeding - Randomized DES ITT | Bleeding was assessed according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) criteria. | 21 months (12-33 months post-index procedure) | 
| MACCE (Death, Myocardial Infarction or Stroke) - Randomized BMS ITT |  | 18 months (12-30 months post-index procedure) | 
| Definite or Probable Stent Thrombosis (ST) - Randomized BMS ITT | ST was assessed according to the Academic Research Consortium (ARC) definitions. | 18 months (12-30 months post-index procedure) | 
| GUSTO Severe or Moderate Bleeding - Randomized BMS ITT | Bleeding was assessed according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) criteria. | 18 months (12-30 months post-index procedure) | 
| MACCE (Death, Myocardial Infarction or Stroke) - Randomized BMS ITT |  | 21 months (12-33 months post-index procedure) | 
| Definite or Probable Stent Thrombosis (ST) - Randomized BMS ITT | ST was assessed according to the Academic Research Consortium (ARC) definitions. | 21 months (12-33 months post-index procedure) | 
| GUSTO Severe or Moderate Bleeding - Randomized BMS ITT | Bleeding was assessed according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) criteria. | 21 months (12-33 months post-index procedure) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Coronary Syndrome, Adverse event, Antiplatelet therapy, Sirolimus, Everolimus, Paclitaxel, Zotarolimus, Bare Metal Stent, Drug Eluting Stent, Clinical Events Committee, Dual antiplatelet therapy, Harvard Clinical Research Institute, Major Adverse Cardiac and Cerebral Event, Major Bleeding, Myocardial infarction, Myocardial ischemia, Percutaneous coronary intervention, Stent placement, Stent Thrombosis, Thienopyridine, Clopidogrel, Prasugrel