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

NCT03274752 | Completed Phase 2 DMC

• 1 other identifier: 2016-00349
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiac Remodeling; Myocardial Infarction

Keywords

Paroxetine

Outcome Measures

Primary Outcomes (1)

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

  Assessment by cardiac magnetic resonance imaging

  12 weeks after randomization

Secondary Outcomes (6)

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

  12 weeks after randomization

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

  12 weeks after randomization

• Difference in late-enhancement

  12 weeks after randomization

• Difference in LVEF between baseline and 12 weeks, and 12 months, respectively

  12 months after randomization

• Major adverse cardiac events

  12 weeks and 12 months after randomization

Study Arms (2)

Paroxetine

EXPERIMENTAL

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

Drug: Paroxetine

Placebo

PLACEBO COMPARATOR

Placebo oral capsule QD per os for 13 weeks

Drug: Placebo oral capsule

Interventions

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.

Also known as: Deroxat

Paroxetine

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Bern University Hospital, Department of Cardiology

Bern, 3010, Switzerland

Location

Related Publications (4)

• 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.

  PMID: 25739765 BACKGROUND

• 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.

  PMID: 10869273 BACKGROUND

• 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.

  PMID: 36000427 DERIVED

• 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.

  PMID: 34259826 DERIVED

MeSH Terms

Conditions

Myocardial Infarction

Interventions

Paroxetine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Thomas Pilgrim, MD

  Bern University Hospital, Department of Cardiology, Freiburgstrasse 10, CH-3010 Bern, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2017
• First Posted: September 7, 2017
• Study Start: October 26, 2017
• Primary Completion: January 1, 2021
• Study Completion: March 1, 2022
• Last Updated: June 1, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)