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Completed

NCT Number: NCT03274752

Paroxetine-mediated GRK2 Inhibition to Reduce Cardiac Remodeling After Acute Myocardial Infarction

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.

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Key information

Conditions

Cardiac Remodeling Cardiovascular Diseases Heart Diseases Infarction Ischemia Myocardial Infarction Myocardial Ischemia Necrosis Pathologic Processes Pathological Conditions, Signs and Symptoms Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Bern University Hospital, Department of Cardiology

Bern, 3010, Switzerland

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

paroxetine

Drug

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 oral capsule

Drug

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.

Primary outcomes

  1. Difference in the change of left ventricular ejection fraction (LVEF)

    Time frame: 12 weeks after randomization

    Assessment by cardiac magnetic resonance imaging

Secondary outcomes

  1. Difference in change in left left-ventricular end-diastolic volume (LVEDV)

    Time frame: 12 weeks after randomization

    Assessment by cardiac magnetic resonance imaging

  2. Difference in change in left left-ventricular end-systolic volume (LVESV)

    Time frame: 12 weeks after randomization

    Assessment by cardiac magnetic resonance imaging

  3. Difference in late-enhancement

    Time frame: 12 weeks after randomization

    Assessment by cardiac magnetic resonance imaging

  4. Difference in LVEF between baseline and 12 weeks, and 12 months, respectively

    Time frame: 12 months after randomization

    Assessment by transthoracic echocardiography

  5. Major adverse cardiac events

    Time frame: 12 weeks and 12 months after randomization

    Cardiac death, myocardial infarction, repeat hospitalization for heart failure

  6. Clinical symptoms of heart failure

    Time frame: 12 weeks and 12 months after randomization

    Assessed by New York Heart Association (NYHA) categorization

Sponsors and collaborators

Lead sponsor

Insel Gruppe AG, University Hospital Bern

Other

Registry information

Official study title

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

Acronym: CARE-AMI

Important dates

Study start
2017
Primary completion
2021
Study completion
2022
First posted
Sep 7, 2017
Registry last updated
Jun 1, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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