Cardiac RemodelingPhase 2CARE-AMINCT03274752
Paroxetine-mediated GRK2 Inhibition to Reduce Cardiac Remodeling After Acute Myocardial Infarction
A Phase 2 study testing Paroxetine in people with Cardiac Remodeling and Myocardial Infarction, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Remodeling, Myocardial Infarction
- What is being tested?
- Paroxetine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteSwitzerland
- Study dates
- 26 Oct 2017to 1 Mar 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Bern University Hospital, Department of Cardiology
Bern, 3010
About this study
Official title: Paroxetine-mediated GRK2 Inhibition to Reduce Cardiac Remodeling After Acute Myocardial Infarction (CARE-AMI): a Randomized Controlled Pilot Study
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.
Read the 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.
- Conditions
- Cardiac Remodeling, Myocardial Infarction
- Being tested
- Paroxetine, Placebo oral capsule
- Keywords
- Paroxetine
- Medical subject headings
- Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParoxetineDrug
Also called Deroxat
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.
Placebo oral capsuleDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Paroxetine | Experimental | Paroxetine 20mg QD per os for 12 weeks followed by 10mg for one additional week Receives: Drug: Paroxetine |
| Placebo | Placebo comparator | Placebo oral capsule QD per os for 13 weeks Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in the change of left ventricular ejection fraction (LVEF)
Assessment by cardiac magnetic resonance imaging
Measured: 12 weeks after randomization
Secondary outcomes (6)
Difference in change in left left-ventricular end-diastolic volume (LVEDV)
Assessment by cardiac magnetic resonance imaging
Measured: 12 weeks after randomization
Difference in change in left left-ventricular end-systolic volume (LVESV)
Assessment by cardiac magnetic resonance imaging
Measured: 12 weeks after randomization
Difference in late-enhancement
Assessment by cardiac magnetic resonance imaging
Measured: 12 weeks after randomization
Difference in LVEF between baseline and 12 weeks, and 12 months, respectively
Assessment by transthoracic echocardiography
Measured: 12 months after randomization
Major adverse cardiac events
Cardiac death, myocardial infarction, repeat hospitalization for heart failure
Measured: 12 weeks and 12 months after randomization
Clinical symptoms of heart failure
Assessed by New York Heart Association (NYHA) categorization
Measured: 12 weeks and 12 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2017
- Study start26 Oct 2017
- Primary completion1 Jan 2021
- Study completion1 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cardiac RemodelingStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thomas Pilgrim, MD, Principal investigator, Bern University Hospital, Department of Cardiology, Freiburgstrasse 10, CH-3010 Bern, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03274752
- Sponsor's protocol ID
- 2016-00349
- Other IDs
- 2016
- Acronym
- CARE-AMI
- Status last verified
- May 2022
- First submitted
- 29 Aug 2017
- Last updated
- 1 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25739765Sutton 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.
PubMed 10869273Pilgrim 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.
PubMed 36000427Pilgrim 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.
PubMed 34259826
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Paroxetine-mediated GRK2 Inhibition to Reduce Cardiac Remodeling After Acute Myocardial Infarction (CARE-AMI): a Randomized Controlled Pilot Study
- ClinicalTrials.gov ID
- NCT03274752
- Acronym / sponsor ID
- CARE-AMI / 2016-00349
- Conditions
- Cardiac Remodeling, Myocardial Infarction
- Keywords
- Paroxetine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 26 Oct 2017 (actual)
- Primary completion
- 1 Jan 2021 (actual)
- Study completion
- 1 Mar 2022 (actual)
- First posted
- 7 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Paroxetine | Experimental | Drug: ParoxetineParoxetine 20mg QD per os for 12 weeks followed by 10mg for one additional week |
| Placebo | Placebo comparator | Drug: Placebo oral capsulePlacebo oral capsule QD per os for 13 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ParoxetineAlso: DeroxatParoxetine (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. | Drug | Paroxetine |
| Placebo oral capsulePlacebo 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. | Drug | Placebo |
Primary outcome
Difference in the change of left ventricular ejection fraction (LVEF)
Time frame: 12 weeks after randomization
Assessment by cardiac magnetic resonance imaging
6 secondary outcomes
Difference in change in left left-ventricular end-diastolic volume (LVEDV)
Time frame: 12 weeks after randomization
Difference in change in left left-ventricular end-systolic volume (LVESV)
Time frame: 12 weeks after randomization
Difference in late-enhancement
Time frame: 12 weeks after randomization
Difference in LVEF between baseline and 12 weeks, and 12 months, respectively
Time frame: 12 months after randomization
Major adverse cardiac events
Time frame: 12 weeks and 12 months after randomization
Clinical symptoms of heart failure
Time frame: 12 weeks and 12 months after randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2022.
- Background: PubMed 25739765Schumacher 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.
- Background: PubMed 10869273Sutton 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.
- Derived from this study: PubMed 36000427Pilgrim 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.
- Derived from this study: PubMed 34259826Pilgrim 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.
- Individual participant dataSharing planned: No
Related trials for Cardiac Remodeling
Recruiting
ELEVATE-HFpEF Clinical Study
Heart Failure With Preserved Ejection Fraction (HFpEF)
Recruiting
AVS Pulse Intravascular Lithotripsy™ (Pulse IVL™) to Open Vessels With Calcific Walls and Enhance Vascular Compliance and Remodeling for Coronary Artery Disease
Coronary Arterial Disease (CAD)
Not yet recruitingObservational study
Metabolic Changes in Heart Failure Patients Treated With Vericiguat
Heart Failure, Worsening Heart Failure
Active, not recruiting
Microvascular Dysfunction Assessment to Predict Left Ventricular Reverse Remodeling
Heart Failure, Left Ventricular Dysfunction
Active, not recruiting
Fast Induced Remodeling in Heart Failure With Preserved Ejection Fraction
Heart Failure With Preserved Ejection Fraction, Concentric Hypertrophy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Pilgrim, MD principal investigator
Bern University Hospital, Department of Cardiology, Freiburgstrasse 10, CH-3010 Bern, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paroxetine in people with Cardiac Remodeling and Myocardial Infarction, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in the change of left ventricular ejection fraction (LVEF) (time frame: 12 weeks after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03274752, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2022.