search
Back to results

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

Primary Purpose

Cardiac Remodeling, Myocardial Infarction

Status
Completed
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
Paroxetine
Placebo oral capsule
Sponsored by
Insel Gruppe AG, University Hospital Bern
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiac Remodeling focused on measuring Paroxetine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Bern University Hospital, Department of Cardiology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Paroxetine

Placebo

Arm Description

Paroxetine 20mg QD per os for 12 weeks followed by 10mg for one additional week

Placebo oral capsule QD per os for 13 weeks

Outcomes

Primary Outcome Measures

Difference in the change of left ventricular ejection fraction (LVEF)
Assessment by cardiac magnetic resonance imaging

Secondary Outcome Measures

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

Full Information

First Posted
August 29, 2017
Last Updated
May 29, 2022
Sponsor
Insel Gruppe AG, University Hospital Bern
search

1. Study Identification

Unique Protocol Identification Number
NCT03274752
Brief Title
Paroxetine-mediated GRK2 Inhibition to Reduce Cardiac Remodeling After Acute Myocardial Infarction
Acronym
CARE-AMI
Official Title
Paroxetine-mediated GRK2 Inhibition to Reduce Cardiac Remodeling After Acute Myocardial Infarction (CARE-AMI): a Randomized Controlled Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
October 26, 2017 (Actual)
Primary Completion Date
January 1, 2021 (Actual)
Study Completion Date
March 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Insel Gruppe AG, University Hospital Bern

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Remodeling, Myocardial Infarction
Keywords
Paroxetine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Paroxetine
Arm Type
Experimental
Arm Description
Paroxetine 20mg QD per os for 12 weeks followed by 10mg for one additional week
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo oral capsule QD per os for 13 weeks
Intervention Type
Drug
Intervention Name(s)
Paroxetine
Other Intervention Name(s)
Deroxat
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
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 Measure Information:
Title
Difference in the change of left ventricular ejection fraction (LVEF)
Description
Assessment by cardiac magnetic resonance imaging
Time Frame
12 weeks after randomization
Secondary Outcome Measure Information:
Title
Difference in change in left left-ventricular end-diastolic volume (LVEDV)
Description
Assessment by cardiac magnetic resonance imaging
Time Frame
12 weeks after randomization
Title
Difference in change in left left-ventricular end-systolic volume (LVESV)
Description
Assessment by cardiac magnetic resonance imaging
Time Frame
12 weeks after randomization
Title
Difference in late-enhancement
Description
Assessment by cardiac magnetic resonance imaging
Time Frame
12 weeks after randomization
Title
Difference in LVEF between baseline and 12 weeks, and 12 months, respectively
Description
Assessment by transthoracic echocardiography
Time Frame
12 months after randomization
Title
Major adverse cardiac events
Description
Cardiac death, myocardial infarction, repeat hospitalization for heart failure
Time Frame
12 weeks and 12 months after randomization
Title
Clinical symptoms of heart failure
Description
Assessed by New York Heart Association (NYHA) categorization
Time Frame
12 weeks and 12 months after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Pilgrim, MD
Organizational Affiliation
Bern University Hospital, Department of Cardiology, Freiburgstrasse 10, CH-3010 Bern, Switzerland
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bern University Hospital, Department of Cardiology
City
Bern
ZIP/Postal Code
3010
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
25739765
Citation
Schumacher SM, Gao E, Zhu W, Chen X, Chuprun JK, Feldman AM, Tesmer JJ, Koch WJ. Paroxetine-mediated GRK2 inhibition reverses cardiac dysfunction and remodeling after myocardial infarction. Sci Transl Med. 2015 Mar 4;7(277):277ra31. doi: 10.1126/scitranslmed.aaa0154.
Results Reference
background
PubMed Identifier
10869273
Citation
Sutton MG, Sharpe N. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation. 2000 Jun 27;101(25):2981-8. doi: 10.1161/01.cir.101.25.2981. No abstract available.
Results Reference
background
PubMed Identifier
36000427
Citation
Pilgrim T, Bernhard B, Furholz M, Vollenbroich R, Babongo Bosombo F, Losdat S, Reusser N, Windecker S, Stortecky S, Siontis GCM, Hunziker L, Lanz J, Dobner S. Paroxetine-Mediated G-Protein Receptor Kinase 2 Inhibition in Patients With Acute Anterior Myocardial Infarction: Final 1-Year Outcomes of the Randomized CARE-AMI Trial. J Am Heart Assoc. 2022 Sep 6;11(17):e026362. doi: 10.1161/JAHA.122.026362. Epub 2022 Aug 24. No abstract available.
Results Reference
derived
PubMed Identifier
34259826
Citation
Pilgrim T, Vollenbroich R, Deckarm S, Grani C, Dobner S, Stark AW, Erne SA, Babongo Bosombo F, Fischer K, Stortecky S, Reusser N, Furholz M, Siontis GCM, Heg D, Hunziker L, Windecker S, Lanz J. Effect of Paroxetine-Mediated G-Protein Receptor Kinase 2 Inhibition vs Placebo in Patients With Anterior Myocardial Infarction: A Randomized Clinical Trial. JAMA Cardiol. 2021 Oct 1;6(10):1171-1176. doi: 10.1001/jamacardio.2021.2247. Erratum In: JAMA Cardiol. 2021 Aug 18;:null.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs