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

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Spontaneous Coronary Artery Dissection
• Intervention / Treatment: Drug: Beta blocker, aspirin, clopidogrel

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 Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Fernando Alfonso, MD; Phone Number: 34 680483165; Email: falf@hotmail.com
• Study Contact Backup: Name: Spanish Society of Cardiology Spanish Society of Cardiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / 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: Aspirin; Clopidogrel; Beta-blockers
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: Aspirin; Clopidogrel; Beta-blockers
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: Aspirin; Clopidogrel; Beta-blockers
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: Aspirin; Clopidogrel; Beta-blockers

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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Spanish Society of Cardiology
• Collaborators: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa; Instituto de Investigación Sanitaria Hospital Universitario de la Princesa
• Investigators: Study Chair: Spanish Society of Cardiology Spanish Society of Cardiology, Spanish Society of Cardiology

Publications and helpful links

General Publications

• Alfonso F, de la Torre Hernandez JM, Ibanez B, Sabate M, Pan M, Gulati R, Saw J, Angiolillo DJ, Adlam D, Sanchez-Madrid F. Rationale and design of the BA-SCAD (Beta-blockers and Antiplatelet agents in patients with Spontaneous Coronary Artery Dissection) randomized clinical trial. Rev Esp Cardiol (Engl Ed). 2022 Jun;75(6):515-522. doi: 10.1016/j.rec.2021.08.003. Epub 2021 Sep 22. English, Spanish.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 30, 2021
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2028

Study Registration Dates

• First Submitted: April 7, 2021
• First Submitted That Met QC Criteria: April 14, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 20, 2021
• Last Update Submitted That Met QC Criteria: April 14, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Coronary angiography; Myocardial infarction; Beta-blockers; Biomarkers; Spontaneous coronary artery dissection; Antiplatelets; Intracoronary imaging
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Heart Defects, Congenital; Cardiovascular Abnormalities; Aneurysm; Vascular Diseases; Aneurysm, Dissecting; Coronary Vessel Anomalies; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Clopidogrel; Adrenergic beta-Antagonists
• Other Study ID Numbers: BA-SCAD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: To be decided by the steering committee upon formal official request by academic investigators
• IPD Sharing Time Frame: After the primary endpoint is reported
• IPD Sharing Access Criteria: To be discussed
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No