Cardiac Remodeling, Myocardial Infarction
Conditions
Keywords
Paroxetine
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.
Interventions
DRUGParoxetine
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.
DRUGPlacebo 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.
Sponsors
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in the change of left ventricular ejection fraction (LVEF) | 12 weeks after randomization | Assessment by cardiac magnetic resonance imaging |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in change in left left-ventricular end-systolic volume (LVESV) | 12 weeks after randomization | Assessment by cardiac magnetic resonance imaging |
| Difference in late-enhancement | 12 weeks after randomization | Assessment by cardiac magnetic resonance imaging |
| Difference in change in left left-ventricular end-diastolic volume (LVEDV) | 12 weeks after randomization | Assessment by cardiac magnetic resonance imaging |
| Major adverse cardiac events | 12 weeks and 12 months after randomization | Cardiac death, myocardial infarction, repeat hospitalization for heart failure |
| Clinical symptoms of heart failure | 12 weeks and 12 months after randomization | Assessed by New York Heart Association (NYHA) categorization |
| Difference in LVEF between baseline and 12 weeks, and 12 months, respectively | 12 months after randomization | Assessment by transthoracic echocardiography |
Countries
Switzerland
Outcome results
None listed