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

• ClinicalTrials.gov Identifier: NCT04850417
• Recruitment Status: Not yet recruiting
• First Posted: April 20, 2021
• Last Update Posted: April 20, 2021
• Sponsor: Spanish Society of Cardiology
• Collaborators: Instituto de Investigación Sanitaria Hospital Universitario de la Princesa; Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
• Information provided by (Responsible Party): Fernando Alfonso, Spanish Society of Cardiology

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 (Clinical Trial)
• Estimated Enrollment: 600 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Intervention Model Description: 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)
• Estimated Study Start Date: April 30, 2021
• Estimated Primary Completion Date: December 31, 2024
• Estimated Study Completion Date: December 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 :

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

1. MACE (death, myocardial infarction, coronary revascularization, stroke and heart failure) [ Time Frame: 1, 2 and 3 years ]
   MACE (death, myocardial infarction, coronary revascularization, stroke and heart failure)
2. MACE (death, myocardial infarction, coronary revascularization) [ Time Frame: 1, 2 and 3 years ]
   MACE (death, myocardial infarction, coronary revascularization)
3. MACE (death, myocardial infarction) [ Time Frame: 1, 2 and 3 years ]
   MACE (death, myocardial infarction)
4. MACE (death, myocardial infarction, coronary revascularization, recurrent SCAD, stroke, unplanned admission for heart failure or acute coronary syndrome with dynamic ECG changes) [ Time Frame: 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)
5. Safety: Major Bleeding [ Time Frame: 1 year ]
   Major Bleeding (BARC >=3)
6. Safety: Bleeding [ Time Frame: 1 year ]
   Bleeding (BARC >=2)
7. MACE and Bleeding [ Time Frame: 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
8. Death [ Time Frame: 1, 2 and 3 years ]
   Death
9. Myocardial infarction [ Time Frame: 1, 2 and 3 years ]
   Myocardial infarction
10. Coronary revascularization [ Time Frame: 1, 2 and 3 years ]
    Coronary revascularization
11. Recurrent SCAD [ Time Frame: 1, 2 and 3 years ]
    Recurrent SCAD
12. Stroke [ Time Frame: 1, 2 and 3 years ]
    Stroke
13. Unplanned admission for heart failure [ Time Frame: 1, 2 and 3 years ]
    Unplanned admission for heart failure
14. Unplanned admission for acute coronary syndrome with dynamic ECG changes [ Time Frame: 1, 2, 3 years ]
    Unplanned admission for acute coronary syndrome with dynamic ECG changes

Other Outcome Measures:

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

Eligibility Criteria

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

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)

Contacts and Locations

Contacts

Contact: Fernando Alfonso, MD; 34 680483165; falf@hotmail.com

Contact: Spanish Society of Cardiology Spanish Society of Cardiology

Sponsors and Collaborators

Spanish Society of Cardiology

Instituto de Investigación Sanitaria Hospital Universitario de la Princesa

Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Investigators

• Study Chair: Spanish Society of Cardiology Spanish Society of Cardiology; Spanish Society of Cardiology

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Fernando Alfonso, Principal Investigator, Spanish Society of Cardiology
• ClinicalTrials.gov Identifier: NCT04850417
• Other Study ID Numbers: BA-SCAD
• First Posted: April 20, 2021
• Last Update Posted: April 20, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

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

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Fernando Alfonso, Spanish Society of Cardiology:

Spontaneous coronary artery dissection; Beta-blockers; Antiplatelets; Coronary angiography; Intracoronary imaging; Biomarkers; Myocardial infarction

Additional relevant MeSH terms:

Aneurysm, Dissecting; Coronary Vessel Anomalies; Vascular Diseases; Aneurysm; Cardiovascular Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Diseases; Congenital Abnormalities; Aspirin; Clopidogrel; Adrenergic beta-Antagonists; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists