Paroxetine-mediated GRK2 Inhibition to Reduce Cardiac Remodeling After Acute Myocardial Infarction
- Conditions
- Myocardial InfarctionCardiac Remodeling
- Interventions
- Drug: Placebo oral capsule
- Registration Number
- NCT03274752
- Lead Sponsor
- Insel Gruppe AG, University Hospital Bern
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
- 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)
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo oral capsule Placebo oral capsule QD per os for 13 weeks Paroxetine Paroxetine Paroxetine 20mg QD per os for 12 weeks followed by 10mg for one additional week
- Primary Outcome Measures
Name Time Method Difference in the change of left ventricular ejection fraction (LVEF) 12 weeks after randomization Assessment by cardiac magnetic resonance imaging
- Secondary Outcome Measures
Name Time Method Major adverse cardiac events 12 weeks and 12 months after randomization Cardiac death, myocardial infarction, repeat hospitalization for heart failure
Difference in change in left left-ventricular end-systolic volume (LVESV) 12 weeks after randomization Assessment by cardiac magnetic resonance imaging
Difference in LVEF between baseline and 12 weeks, and 12 months, respectively 12 months after randomization Assessment by transthoracic echocardiography
Difference in change in left left-ventricular end-diastolic volume (LVEDV) 12 weeks after randomization Assessment by cardiac magnetic resonance imaging
Difference in late-enhancement 12 weeks after randomization Assessment by cardiac magnetic resonance imaging
Clinical symptoms of heart failure 12 weeks and 12 months after randomization Assessed by New York Heart Association (NYHA) categorization
Trial Locations
- Locations (1)
Bern University Hospital, Department of Cardiology
🇨🇭Bern, Switzerland