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

NCT ID: NCT03686696

Last Updated: 2023-11-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

198 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-16

Study Completion Date

2023-08-22

Brief Summary

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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%.

Detailed Description

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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

Conditions

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Myocardial Infarction With Non-obstructive Coronary Arteries

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

2 \* 2 Factorial Design
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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No Beta blocker and no ACEI/ARB

No Beta blocker and no ACEI/ARB

Group Type NO_INTERVENTION

No interventions assigned to this group

Beta blocker and ACEI/ARB

Beta blocker and either ACE inhibitor or Angiotensin receptor blocker

Group Type EXPERIMENTAL

Beta blocker

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Beta blocker alone

Beta blocker alone

Group Type EXPERIMENTAL

Beta blocker

Intervention Type DRUG

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/ARB alone

Either ACE inhibitor or Angiotensin receptor blocker alone

Group Type EXPERIMENTAL

ACEI

Intervention Type DRUG

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

Intervention Type DRUG

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

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

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

Intervention Type DRUG

Other Intervention Names

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Beta receptor blocker ACE inhibitor Angiotensin receptor blocker

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Karolinska Institutet

OTHER

Sponsor Role collaborator

Göteborg University

OTHER

Sponsor Role collaborator

University of Leeds

OTHER

Sponsor Role collaborator

University of Adelaide

OTHER

Sponsor Role collaborator

Oslo University Hospital

OTHER

Sponsor Role collaborator

New York University

OTHER

Sponsor Role collaborator

Uppsala University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bertil Lindahl, Prof

Role: STUDY_CHAIR

Uppsala University

Locations

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Royal Adelaide Hospital

Adelaide, Sout Australi, Australia

Site Status

The Lyell McEwin Hospital

Adelaide, , Australia

Site Status

The Queen Elizabeth Hospital

Adelaide, , Australia

Site Status

Gold Coast Hospital

Gold Coast, , Australia

Site Status

Sunshine Hospital

Melbourne, , Australia

Site Status

Royal Perth Hospital

Perth, , Australia

Site Status

Gosford Hospital

Sydney, , Australia

Site Status

John Hunter Hospital

Sydney, , Australia

Site Status

Auckland University Hospital

Auckland, , New Zealand

Site Status

Haukeland University Hospital

Bergen, , Norway

Site Status

Oslo University Hospital

Oslo, , Norway

Site Status

Getafe University Hospital

Getafe, , Spain

Site Status

C.H.U. Ourense

Ourense, , Spain

Site Status

C.H. Universitario de Santiago

Santiago de Compostela, , Spain

Site Status

Mälardalens sjukhus Eskilstuna

Eskilstuna, , Sweden

Site Status

Falu Lasarett

Falun, , Sweden

Site Status

Gävle sjukhus

Gävle, , Sweden

Site Status

Sahlgrenska Universitetssjukhus, Sahlgrenska

Gothenburg, , Sweden

Site Status

Hallands sjukhus

Halmstad, , Sweden

Site Status

Helsingborg Lasarett

Helsingborg, , Sweden

Site Status

Ryhovs sjukhus

Jönköping, , Sweden

Site Status

Centralsjukhuset Karlstad

Karlstad, , Sweden

Site Status

Västmanlands sjukhus Köping

Köping, , Sweden

Site Status

Universitetssjukhuset i Linköping

Linköping, , Sweden

Site Status

Skånes Universitetssjukhus Lund

Lund, , Sweden

Site Status

Skånes universtitetssjukhus Malmö

Malmo, , Sweden

Site Status

Vrinneviesjukhuset

Norrköping, , Sweden

Site Status

Örebro University Hospital

Örebro, , Sweden

Site Status

Danderyd Hospital

Stockholm, , Sweden

Site Status

Söderskjukhuset

Stockholm, , Sweden

Site Status

Akademiska Sjukhuset

Uppsala, , Sweden

Site Status

Västerås Lasarett

Västerås, , Sweden

Site Status

Countries

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Australia New Zealand Norway Spain Sweden

References

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Nordenskjold AM, Agewall S, Atar D, Baron T, Beltrame J, Bergstrom O, Erlinge D, Gale CP, Lopez-Pais J, Jernberg T, Johansson P, Ravn-Fisher A, Reynolds HR, Somaratne JB, Tornvall P, Lindahl B. Randomized evaluation of beta blocker and ACE-inhibitor/angiotensin receptor blocker treatment in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA-BAT): Rationale and design. Am Heart J. 2021 Jan;231:96-104. doi: 10.1016/j.ahj.2020.10.059. Epub 2020 Oct 24.

Reference Type DERIVED
PMID: 33203618 (View on PubMed)

Other Identifiers

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EudraCT number 2018-000889-11

Identifier Type: -

Identifier Source: org_study_id