Paroxetine-mediated GRK2 Inhibition to Reduce Cardiac Remodeling After Acute Myocardial Infarction (CARE-AMI)

May 29, 2022 updated by: University Hospital Inselspital, Berne

Paroxetine-mediated GRK2 Inhibition to Reduce Cardiac Remodeling After Acute Myocardial Infarction (CARE-AMI): a Randomized Controlled Pilot Study

This study evaluates the off-target effect of paroxetine to reverse cardiac remodeling and improve left ventricular ejection fraction in patients after acute myocardial infarction. Half of the participants will receive paroxetine, while the other half will receive placebo treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Cardiac remodeling is characterized by a composite of structural, geometric, molecular, and functional changes of the myocardium, and is an important determinant of heart failure and cardiovascular outcome in survivors of acute myocardial infarction. Progression of heart failure secondary to the remodeling process results from dysregulation of the G protein-coupled receptor (GPCR). Excessive adrenergic drive in patients with heart failure results in an enhanced activation of GPCR kinases (GRKs) that is considered to have a central role in adverse cardiac remodeling after ischemic injury. The selective Serotonin reuptake inhibitor paroxetine specifically binds to the catalytic domain of GRK2 as an off-target effect, and has been shown to reverse cardiac remodeling and increase left ventricular ejection fraction in a mouse model. The effect was observed at serum levels achieved with standard dosages of paroxetine, and was robust in mice with and without concomitant heart failure treatment, respectively.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Bern, Switzerland, 3010
        • Bern University Hospital, Department of Cardiology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Anterior wall ST-segment elevation myocardial infarction
  • Primary percutaneous coronary intervention (PCI) within 24 hours of symptom onset
  • Left ventricular ejection fraction ≤ 45% within 48-96 hours after primary PCI (transthoracic echocardiography)

Exclusion Criteria:

  • Female patients at reproductive age (<50 years)
  • Known intolerance to paroxetine
  • Inability to provide informed consent
  • Currently participating in another trial before reaching first endpoint
  • Current medical therapy with MAO-blocker (during, 14 days before, and 14 days after treatment with MAO-blocker), lithium, thioridazide, or pimozide
  • Concomitant tamoxifen intake
  • Previous myocardial infarction
  • Previous revascularization procedure (percutaneous coronary intervention or coronary artery bypass grafting).
  • Contraindication to cardiac magnetic resonance imaging
  • Obvious or questionable inability to appropriately cooperate (alcohol, drugs etc.)
  • Relevant nephropathy or hepatopathy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Paroxetine
Paroxetine 20mg QD per os for 12 weeks followed by 10mg for one additional week
Drug: Paroxetine
Paroxetine (Deroxat) will be administered in a dosage of 20mg q.d. per os continuously for 12 weeks after primary PCI. In week 13, Paroxetine (Deroxat) will be administered in a dosage of 10mg q.d. per os.
Other Names:
  • Deroxat
Placebo Comparator: Placebo
Placebo oral capsule QD per os for 13 weeks
Drug: Placebo oral capsule
Placebo will be given q.d. per os continuously for 12 weeks after primary PCI. In addition, a placebo will be given q.d. per os in week 13 as well.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in the change of left ventricular ejection fraction (LVEF)
Time Frame: 12 weeks after randomization
Assessment by cardiac magnetic resonance imaging
12 weeks after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in change in left left-ventricular end-diastolic volume (LVEDV)
Time Frame: 12 weeks after randomization
Assessment by cardiac magnetic resonance imaging
12 weeks after randomization
Difference in change in left left-ventricular end-systolic volume (LVESV)
Time Frame: 12 weeks after randomization
Assessment by cardiac magnetic resonance imaging
12 weeks after randomization
Difference in late-enhancement
Time Frame: 12 weeks after randomization
Assessment by cardiac magnetic resonance imaging
12 weeks after randomization
Difference in LVEF between baseline and 12 weeks, and 12 months, respectively
Time Frame: 12 months after randomization
Assessment by transthoracic echocardiography
12 months after randomization
Major adverse cardiac events
Time Frame: 12 weeks and 12 months after randomization
Cardiac death, myocardial infarction, repeat hospitalization for heart failure
12 weeks and 12 months after randomization
Clinical symptoms of heart failure
Time Frame: 12 weeks and 12 months after randomization
Assessed by New York Heart Association (NYHA) categorization
12 weeks and 12 months after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Inselspital, Berne

Investigators

  • Principal Investigator: Thomas Pilgrim, MD, Bern University Hospital, Department of Cardiology, Freiburgstrasse 10, CH-3010 Bern, Switzerland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 26, 2017

Primary Completion (Actual)

January 1, 2021

Study Completion (Actual)

March 1, 2022

Study Registration Dates

First Submitted

August 29, 2017

First Submitted That Met QC Criteria

September 4, 2017

First Posted (Actual)

September 7, 2017

Study Record Updates

Last Update Posted (Actual)

June 1, 2022

Last Update Submitted That Met QC Criteria

May 29, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-00349

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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