Clinical trial NCT04850417: Randomized Study of Beta-Blockers and Antiplatelets in Patients With Spontaneous Coronary Artery Dissection
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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Spontaneous Coronary Artery Dissection
Keywords: Spontaneous coronary artery dissection
Beta-blockers
Antiplatelets
Coronary angiography
Intracoronary imaging
Biomarkers
Myocardial infarction
Lead sponsor: Spanish Society of Cardiology
Sponsor class: OTHER
Collaborators: name: Instituto de Investigación Sanitaria Hospital Universitario de la Princesa
name: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
First posted: 2021-04-20
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Factorial 2x2 design (a) beta-blockers yes/no; b) Antiplatelets short/long)
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: MACE (death, myocardial infarction, coronary revascularization, recurrent SCAD, stroke, unplanned admission for heart failure or acute coronary syndrome with dynamic ECG changes)
timeFrame: 1 year
Secondary outcomes:
measure: MACE (death, myocardial infarction, coronary revascularization, stroke and heart failure)
timeFrame: 1, 2 and 3 years
measure: MACE (death, myocardial infarction, coronary revascularization)
timeFrame: 1, 2 and 3 years
measure: MACE (death, myocardial infarction)
timeFrame: 1, 2 and 3 years
measure: MACE (death, myocardial infarction, coronary revascularization, recurrent SCAD, stroke, unplanned admission for heart failure or acute coronary syndrome with dynamic ECG changes)
timeFrame: 2, 3,4 and 5 years
measure: Safety: Major Bleeding
timeFrame: 1 year
measure: Safety: Bleeding
timeFrame: 1 year
measure: MACE and Bleeding
timeFrame: 1, 2 and 3 years
measure: Death
timeFrame: 1, 2 and 3 years
measure: Myocardial infarction
timeFrame: 1, 2 and 3 years
measure: Coronary revascularization
timeFrame: 1, 2 and 3 years
measure: Recurrent SCAD
timeFrame: 1, 2 and 3 years
measure: Stroke
timeFrame: 1, 2 and 3 years
measure: Unplanned admission for heart failure
timeFrame: 1, 2 and 3 years
measure: Unplanned admission for acute coronary syndrome with dynamic ECG changes
timeFrame: 1, 2, 3 years
Other outcomes:
measure: Substudy on strategies and results of coronary interventions
timeFrame: Through study completion, up to 5 years
measure: Substudy on angiographic findings in relation to prognosis
timeFrame: Through study completion, up to 5 years
measure: Substudy on value of intracoronary imaging in SCAD (OCT and IVUS)
timeFrame: Through study completion, up to 5 years
measure: Non-invasive imaging techniques
timeFrame: Through study completion, up to 5 years
measure: Substudy on inflammation and biomarkers
timeFrame: Through study completion, up to 5 years
measure: Pharmacogenomic study
timeFrame: Through study completion, up to 5 years
measure: Micro RNAs and Genetic studies
timeFrame: Through study completion, up to 5 years
Locations:
Study officials:
affiliation: Spanish Society of Cardiology
name: Spanish Society of Cardiology Spanish Society of Cardiology
role: STUDY_CHAIR
References:
citation: 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.