Randomized Evaluation of Beta Blocker and ACEI/ARB Treatment in MINOCA Patients - MINOCA-BAT

Myocardial Infarction With Non-obstructive Coronary Arteries Clinical Trial

— MINOCA-BAT  

Official title:

Randomized Evaluation of Beta Blocker and Angiotensin Converting Enzyme Inhibitor (ACEI) /Angiotensin Receptor Blocker (ARB) Treatment in MINOCA Patients.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03686696
• Other study ID #: EudraCT number 2018-000889-11
• Status: Terminated
• Phase: Phase 4
• Start date: December 16, 2018
• Est. completion date: August 22, 2023

Study information

• Verified date: November 2023
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Myocardial infarction with non-obstructive coronary arteries" (MINOCA) occurs in 5-10% of all patients with AMI. There are neither any randomized clinical trials in MINOCA patients evaluating effects of secondary preventive treatments proven beneficial in patients with classic AMI, nor any treatment guidelines.

The primary objective of this multi-national, multi-center pragmatic randomized clinical trial is to determine whether oral beta-blockade compared to no oral beta-blockade, and whether Angiotensin Converting Enzyme Inhibitors (ACEI/ Angiotensin Receptor Blockers (ARB) compared to no ACEI/ARB, reduce the composite endpoint of death of any cause and readmission because of AMI, ischemic stroke or heart failure in patients discharged with myocardial infarction with non-obstructive coronary artery disease (MINOCA) and with no clinical signs of heart failure and with left ventricular (LV) systolic ejection fraction ≥40%.

Description:

Large-scale use of acute coronary angiography has revealed a large portion of AMI without angiographically obstructive (defined as ≥50% diameter stenosis) coronary artery disease (CAD). The term "myocardial infarction with non-obstructive coronary arteries" (MINOCA) has been coined for this entity. MINOCA occurs in 5-10% of all patients with AMI and these patients are younger and more often females compared to patients with AMI and obstructive CAD. The 1-year mortality after MINOCA was found to be 3.5% in the systematic review by Pasupathy et al.. There are no randomized clinical trials in MINOCA patients evaluating effects of secondary preventive treatments proven beneficial in patients with classic AMI. However, in an observational study with propensity score matched comparisons the risk of experiencing a Major Adverse Cardiac Event (MACE) was 18% lower in patients treated with ACEI/ARB compared to no ACEI/ARB; in patients on beta blockers compared to patients not using beta blockers there was a non-significant 14% reduction in MACE.

The primary objective of this multi-national, multi-center pragmatic randomized clinical trial is to determine whether oral beta-blockade compared to no oral beta-blockade, and whether ACEI/ARB compared to no ACEI/ARB, reduce the composite endpoint of death of any cause and readmission because of AMI, ischemic stroke or heart failure in patients discharged with myocardial infarction with non-obstructive coronary artery disease (MINOCA) and with no clinical signs of heart failure and with LV systolic ejection fraction ≥40%.

PRIMARY ENDPOINT: Time to death of any cause or readmission because of myocardial infarction, ischemic stroke or heart failure.

SECONDARY ENDPOINTS:

Time to:

• All-cause mortality

• Cardiovascular mortality

• Readmission because of AMI

• Readmission because of ischemic stroke

• Readmission because of heart failure

• Readmission because of unstable angina pectoris

• Readmission because of atrial fibrillation.

Safety:

Time to readmission because of:

• AV-block II-III, hypotension, syncope or need for pacemaker

• Acute kidney injury

• Ventricular tachycardia/fibrillation

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 198
• Est. completion date: August 22, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >18 years.

• A clinical diagnosis of MINOCA within the last 30 days.

• Left ventricular ejection fraction =40% measured with echocardiography, MRI or left ventriculography after admission and prior to randomization.

• Written informed consent obtained

Exclusion Criteria:

• Any condition that may influence the patient's ability to comply with study protocol.

• Previous revascularization (CABG or PCI)

• Clinical signs of heart failure

• MRI-proven myocarditis or a strong clinical suspicion of myocarditis or takotsubo as cause of the index event

• Contraindications for Beta blocker treatment

• Contraindications for ACEI and ARB treatment

• Prior use of ACEI, ARB, or Beta blockers, which must continue according to treating physician.

• New indication for Beta blocker or ACEI/ARB treatment other than as secondary prevention according to treating physician

• Ongoing pregnancy or woman of childbearing potential not using adequate contraceptives

• Participation in a trial evaluating a drug known to interact with Beta blockers or ACEI/ARB

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• Myocardial Infarction With Non-obstructive Coronary Arteries

Intervention

Drug:
• Beta blocker
Patients randomized to beta-blockade will be administered the assigned treatment during the rest of the hospital stay and receive a prescription for the continued use at discharge. The treating physician is encouraged to aim for target dose or highest tolerable dose for the drug. Patients will be encouraged to continue the use of the randomized treatment following discharge until contraindications.
• ACEI
Patients randomized to ACE inhibitor will be administered the assigned treatment during the rest of the hospital stay and receive a prescription for the continued use at discharge. The treating physician is encouraged to aim for target dose or highest tolerable dose for the drug. Patients will be encouraged to continue the use of the randomized treatment following discharge until contraindications.
• ARB
Patients randomized to Angiotensin receptor blockers will be administered the assigned treatment during the rest of the hospital stay and receive a prescription for the continued use at discharge. The treating physician is encouraged to aim for target dose or highest tolerable dose for the drug. Patients will be encouraged to continue the use of the randomized treatment following discharge until contraindications

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	Sout Australi
Australia	The Lyell McEwin Hospital	Adelaide
Australia	The Queen Elizabeth Hospital	Adelaide
Australia	Gold Coast Hospital	Gold Coast
Australia	Sunshine Hospital	Melbourne
Australia	Royal Perth Hospital	Perth
Australia	Gosford Hospital	Sydney
Australia	John Hunter Hospital	Sydney
New Zealand	Auckland University Hospital	Auckland
Norway	Haukeland University Hospital	Bergen
Norway	Oslo University Hospital	Oslo
Spain	Getafe University Hospital	Getafe
Spain	C.H.U. Ourense	Ourense
Spain	C.H. Universitario de Santiago	Santiago De Compostela
Sweden	Mälardalens sjukhus Eskilstuna	Eskilstuna
Sweden	Falu Lasarett	Falun
Sweden	Gävle sjukhus	Gävle
Sweden	Sahlgrenska Universitetssjukhus, Sahlgrenska	Göteborg
Sweden	Hallands sjukhus	Halmstad
Sweden	Helsingborg Lasarett	Helsingborg
Sweden	Ryhovs sjukhus	Jönköping
Sweden	Centralsjukhuset Karlstad	Karlstad
Sweden	Västmanlands sjukhus Köping	Köping
Sweden	Universitetssjukhuset i Linköping	Linköping
Sweden	Skånes Universitetssjukhus Lund	Lund
Sweden	Skånes universtitetssjukhus Malmö	Malmö
Sweden	Vrinneviesjukhuset	Norrköping
Sweden	Örebro University Hospital	Örebro
Sweden	Danderyd Hospital	Stockholm
Sweden	Söderskjukhuset	Stockholm
Sweden	Akademiska Sjukhuset	Uppsala
Sweden	Västerås Lasarett	Västerås

Sponsors (7)

Lead Sponsor	Collaborator
Uppsala University	Göteborg University, Karolinska Institutet, New York University, Oslo University Hospital, University of Adelaide, University of Leeds

Countries where clinical trial is conducted

Australia,  New Zealand,  Norway,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to death of any cause, or time to readmission because of AMI, ischemic stroke or heart failure	A Composite of time to all-cause Death and time to re-admission because of AMI, ischemic stroke or heart failure	Time to event from the date of enrollment through study completion, an average of 4 years.
Secondary	a All-cause death b Cardiovascular death c Readmission because of AMI d Readmission because of ischemic stroke e Readmission because of heart failure f Readmission because of unstable angina pectoris g Readmission because of atrial fibrillation.		a All-cause death: Time to event from the date of enrollment through study completion, an average of 4 years.