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

Sponsor

Spanish Society of Cardiology (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04850417

Collaborator

Instituto de Investigación Sanitaria Hospital Universitario de la Princesa (Other), Fundación de Investigación Biomédica - Hospital Universitario de La Princesa (Other)

600

Enrollment

Arms

92.1

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Spontaneous Coronary Artery Dissection	Drug: Beta blocker, aspirin, clopidogrel	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

600 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Intervention Model Description:

Factorial 2x2 design (a) beta-blockers yes/no; b) Antiplatelets short/long)Factorial 2x2 design (a) beta-blockers yes/no; b) Antiplatelets short/long)

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Apr 30, 2021

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Beta-blockers and Short Antiplatelet Therapy 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 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 Other Names: Beta-blockers Aspirin Clopidogrel
Experimental: Beta-blockers and Long Antiplatelet Therapy 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 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 Other Names: Beta-blockers Aspirin Clopidogrel
Experimental: No Beta-blockers and Short Antiplatelet Therapy 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 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 Other Names: Beta-blockers Aspirin Clopidogrel
Active Comparator: No Beta-blockers and Long Antiplatelet Therapy 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 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 Other Names: Beta-blockers Aspirin Clopidogrel

Outcome Measures

Primary Outcome Measures

MACE (death, myocardial infarction, coronary revascularization, recurrent SCAD, stroke, unplanned admission for heart failure or acute coronary syndrome with dynamic ECG changes) [1 year]
MACE (death, myocardial infarction, coronary revascularization, recurrent SCAD, stroke, unplanned admission for heart failure or acute coronary syndrome with dynamic ECG changes)

Secondary Outcome Measures

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

Other Outcome Measures

Substudy on strategies and results of coronary interventions [Through study completion, up to 5 years]
Strategies and results of coronary interventions (different devices and modalities). Procedural success and angiographic results
Substudy on angiographic findings in relation to prognosis [Through study completion, up to 5 years]
Angiographic analysis (visual and QCA, central corelab). Quantitative coronary angiography analyses (MLD, % diameter stenosis, TIMI Flow)
Substudy on value of intracoronary imaging in SCAD (OCT and IVUS) [Through study completion, up to 5 years]
Intracoronary imaging in SCAD (central corelab) (OCT [optical coherence tomography] and IVUS [intravascular ultrasound] ). Minimal lumen area.
Non-invasive imaging techniques [Through study completion, up to 5 years]
Cardiac CT and CMR (coronary and peripheral arteries) (central corelab)
Substudy on inflammation and biomarkers [Through study completion, up to 5 years]
Comprehensive analysis of biomarkers. Coordinating center (HULP). Including leucocytes, HsCRP, IL6
Pharmacogenomic study [Through study completion, up to 5 years]
Pharmacogenomic study. Coordinating center (HULP). Percent of responders to treatment according to the pharmacogenomic profile
Micro RNAs and Genetic studies [Through study completion, up to 5 years]
Micro RNAs and Genetic studies. Coordinating center (HULP). Array of different micro-RNAs

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)