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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03274752
Recruitment Status : Active, not recruiting
First Posted : September 7, 2017
Last Update Posted : November 13, 2020
Sponsor:
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cardiac Remodeling Myocardial Infarction Drug: Paroxetine Drug: Placebo oral capsule Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Paroxetine-mediated GRK2 Inhibition to Reduce Cardiac Remodeling After Acute Myocardial Infarction (CARE-AMI): a Randomized Controlled Pilot Study
Actual Study Start Date : October 26, 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : September 2021


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 Name: 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.




Primary Outcome Measures :
  1. Difference in the change of left ventricular ejection fraction (LVEF) [ Time Frame: 12 weeks after randomization ]
    Assessment by cardiac magnetic resonance imaging


Secondary Outcome Measures :
  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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03274752


Locations
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Switzerland
Bern University Hospital, Department of Cardiology
Bern, Switzerland, 3010
Sponsors and Collaborators
University Hospital Inselspital, Berne
Investigators
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Principal Investigator: Thomas Pilgrim, MD Bern University Hospital, Department of Cardiology, Freiburgstrasse 10, CH-3010 Bern, Switzerland
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT03274752    
Other Study ID Numbers: 2016-00349
First Posted: September 7, 2017    Key Record Dates
Last Update Posted: November 13, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital Inselspital, Berne:
Paroxetine
Additional relevant MeSH terms:
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Myocardial Infarction
Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Paroxetine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors