Randomized Study of Beta-Blockers and Antiplatelets in Patients With Spontaneous Coronary Artery Dissection

Study Overview
=================
Brief Summary
-----------------
Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome (ACS). Most patients are treated with beta-blockers (BB) and antiplatelet drugs (AP) on empiric basis. The Beta-Blockers and Antiplatelet Agents in Patients with Spontaneous Coronary Artery Dissection (BA-SCAD) randomized clinical trial is an academic, pragmatic, nation-wide, prospective study developed under the auspices of the Spanish Society of Cardiology (SEC) that aims to assess the efficacy of medical therapy in SCAD patients. Using a factorial 2x2 design, patients will be randomized (1:1/1:1) to: 1) BB (yes/no) and 2) short AP regimen (1 month) vs prolonged dual AP therapy (DAPT) (12 months).Only patients with preserved left ventricular ejection fraction (LVEF) will be randomized to BB (yes/no) because patients with LVEF <40% will receive BB according to current guidelines. Likewise, only medically managed patients will be randomized to short AP therapy vs 1-year DAPT. The study will have a pragmatic, open label, blind outcomes design (PROBE). A total of 600 SCAD patients will be randomized within 2 years (300 per arm in a factorial 2x2 design). The primary efficacy endpoint will include the composite of death, acute myocardial infarction (MI), stroke, coronary revascularization, recurrent SCAD, and unplanned hospitalization for ACS or heart failure at 1 year. The primary safety endpoint will be bleeding. All patients will be clinically followed yearly. The main study will be pragmatic but a comprehensive set of additional studies (clinical, imaging, biomarkers, inflammatory, immunologic, pharmacogenetic and genetic) will be organized to ensure an holistic view on this challenging condition.

Detailed Description
-----------------
Spontaneous coronary artery dissection (SCAD) is a relatively rare but important and increasingly recognized cause of acute coronary syndrome (ACS). Most patients presenting with SCAD are treated with beta-blockers (BB) and antiplatelet drugs (AP). Although appealing from a pathophysiological standpoint, such management strategy is completely empiric. The Beta-Blockers and Antiplatelet Agents in Patients with Spontaneous Coronary Artery Dissection (BA-SCAD) randomized clinical trial is an academic, pragmatic, nation-wide, prospective study developed under the auspices of the Spanish Society of Cardiology (SEC) that aims to assess the efficacy of medical therapy in SCAD patients. Using a factorial 2x2 design, patients will be randomized (1:1/1:1) to: 1) BB (yes/no) and 2) short AP regimen (1 month) vs prolonged dual AP therapy (DAPT) (12 months). A conservative medical management will be initially recommended, with coronary revascularization reserved for patients with ongoing/refractory ischemia. Only patients with preserved left ventricular ejection fraction (LVEF) will be randomized to BB (yes/no) because patients with LVEF <40% will receive BB according to current guidelines. Likewise, only medically managed patients will be randomized to short AP therapy vs 1-year DAPT, because patients requiring coronary interventions will receive DAPT. The study will have a pragmatic, open label, blind outcomes design (PROBE). The type and dose of BB and AP agents will be at the discretion of the treating physician. Treatment adherence will be reinforced and closely monitored and the potential influence of drug discontinuation/cross-over on outcomes will be carefully evaluated. A total of 600 SCAD patients will be randomized within 2 years (300 per arm in a factorial 2x2 design). The primary efficacy endpoint will include the composite of death, acute myocardial infarction (MI), stroke, coronary revascularization, recurrent SCAD, and unplanned hospital admission for ACS or heart failure at 1 year. The primary safety endpoint will be bleeding according the Bleeding Academic Research Consortium (BARC) criteria ≥ 3. An analysis of net clinical benefit, including primary efficacy and safety endpoints, will also be performed. All patients will be clinically followed at 1 year (primary endpoint) and yearly thereafter. Although the main study will be pragmatic, following routine clinical practice, a systematic and comprehensive set of additional ancillary studies and investigations (clinical, imaging, biomarkers, inflammatory, immunologic, pharmacogenetic and genetic) will be prospectively organized to ensure a multidisciplinary and holistic view on this challenging condition.

Official Title
-----------------
Randomized Clinical Trial Assessing the Value of Beta-Blockers and Antiplatelet Agents in Patients With Spontaneous Coronary Artery Dissection. (The BA-SCAD Randomized Clinical Trial)

Conditions
-----------------
Spontaneous Coronary Artery Dissection

Intervention / Treatment
-----------------
* Drug: Beta blocker, aspirin, clopidogrel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Angiographic diagnosis of SCAD Admission for ACS or other manifestations of ischemia Informed consent Exclusion Criteria: Cardiogenic shock or severe hemoynamic instability Concomitant severe heart disease requiring surgical correction (in <2 years) Medical condition seriously limiting life expectancy (< 2 years) Allergies or contraindication to drugs required in one of the study arms; the patient may be randomized in the other arm (factorial design)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Factorial 2x2 design (a) beta-blockers yes/no; b) Antiplatelets short/long)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Beta-blockers and Short Antiplatelet Therapy<br>Beta-blockers (experimental) and Short Antiplatelet Therapy (experimental). Aspirin alone recommended for Short Antiplatelet Therapy (The main comparison of this randomized clinical trial (2x2, factorial design) is beta-blockers vs no beta-blockers and short vs long-term antiplatelet therapy) | Drug: Beta blocker, aspirin, clopidogrel<br>* Pragmatic design. Beta-blockers and Antiplatelets drugs selected by the investigators. Asprin and Clopidogrel recomended for patients allocated to prologed DAPT. Aspirin Alone recomended for patients allocated to short antiplatelet therapy<br>* Other names: Clopidogrel;|
| Experimental: Beta-blockers and Long Antiplatelet Therapy<br>Beta-blockers (experimental) and Long Antiplatelet Therapy. Aspirin and Clopidogrel recommended in Long Antiplatelet Therapy (The main comparison of this randomized clinical trial (2x2, factorial design) is beta-blockers vs no beta-blockers and short vs long-term antiplatelet therapy) | Drug: Beta blocker, aspirin, clopidogrel<br>* Pragmatic design. Beta-blockers and Antiplatelets drugs selected by the investigators. Asprin and Clopidogrel recomended for patients allocated to prologed DAPT. Aspirin Alone recomended for patients allocated to short antiplatelet therapy<br>* Other names: Clopidogrel;|
| Experimental: No Beta-blockers and Short Antiplatelet Therapy<br>No Beta-blockers and Short Antiplatelet Therapy (experimental). Aspirin alone recommended in Short Antiplatelet Therapy (The main comparison of this randomized clinical trial (2x2, factorial design) is beta-blockers vs no beta-blockers and short vs long-term antiplatelet therapy) | Drug: Beta blocker, aspirin, clopidogrel<br>* Pragmatic design. Beta-blockers and Antiplatelets drugs selected by the investigators. Asprin and Clopidogrel recomended for patients allocated to prologed DAPT. Aspirin Alone recomended for patients allocated to short antiplatelet therapy<br>* Other names: Clopidogrel;|
| Active Comparator: No Beta-blockers and Long Antiplatelet Therapy<br>No Beta-blockers and Long Antiplatelet Therapy. Aspirin and Clopidogrel recommended in Long Antiplatelet Therapy (The main comparison of this randomized clinical trial (2x2, factorial design) is beta-blockers vs no beta-blockers and short vs long-term antiplatelet therapy) | Drug: Beta blocker, aspirin, clopidogrel<br>* Pragmatic design. Beta-blockers and Antiplatelets drugs selected by the investigators. Asprin and Clopidogrel recomended for patients allocated to prologed DAPT. Aspirin Alone recomended for patients allocated to short antiplatelet therapy<br>* Other names: Clopidogrel;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACE (death, myocardial infarction, coronary revascularization, recurrent SCAD, stroke, unplanned admission for heart failure or acute coronary syndrome with dynamic ECG changes) | MACE (death, myocardial infarction, coronary revascularization, recurrent SCAD, stroke, unplanned admission for heart failure or acute coronary syndrome with dynamic ECG changes) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACE (death, myocardial infarction, coronary revascularization, stroke and heart failure) | MACE (death, myocardial infarction, coronary revascularization, stroke and heart failure) | 1, 2 and 3 years | 
| MACE (death, myocardial infarction, coronary revascularization) | MACE (death, myocardial infarction, coronary revascularization) | 1, 2 and 3 years | 
| MACE (death, myocardial infarction) | MACE (death, myocardial infarction) | 1, 2 and 3 years | 
| MACE (death, myocardial infarction, coronary revascularization, recurrent SCAD, stroke, unplanned admission for heart failure or acute coronary syndrome with dynamic ECG changes) | MACE (death, myocardial infarction, coronary revascularization, recurrent SCAD, stroke, unplanned admission for heart failure or acute coronary syndrome with dynamic ECG changes) | 2, 3,4 and 5 years | 
| Safety: Major Bleeding | Major Bleeding (BARC >=3) | 1 year | 
| Safety: Bleeding | Bleeding (BARC >=2) | 1 year | 
| MACE and Bleeding | MACE (death, myocardial infarction, coronary revascularization, recurrent SCAD, stroke, unplanned admission for heart failure or acute coronary syndrome with dynamic ECG changes) and bleeding | 1, 2 and 3 years | 
| Death | Death | 1, 2 and 3 years | 
| Myocardial infarction | Myocardial infarction | 1, 2 and 3 years | 
| Coronary revascularization | Coronary revascularization | 1, 2 and 3 years | 
| Recurrent SCAD | Recurrent SCAD | 1, 2 and 3 years | 
| Stroke | Stroke | 1, 2 and 3 years | 
| Unplanned admission for heart failure | Unplanned admission for heart failure | 1, 2 and 3 years | 
| Unplanned admission for acute coronary syndrome with dynamic ECG changes | Unplanned admission for acute coronary syndrome with dynamic ECG changes | 1, 2, 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Spontaneous coronary artery dissection, Beta-blockers, Antiplatelets, Coronary angiography, Intracoronary imaging, Biomarkers, Myocardial infarction