- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06342141
Empagliflozin for No-reflow Phenomenon in PCI for STEMI (EMPA-PCI)
Empagliflozin for Reducing the Risk of No-Reflow Phenomenon in Patients Undergoing Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction
Myocardial infarction remains, in our current era, a leading cause of morbidity and mortality both domestically and globally. A significant contributor to this issue is reperfusion injury, which enlarges the infarction, deteriorates ventricular function, leads to poorer outcomes, and currently has no specific treatment. Originally developed as an antidiabetic, empagliflozin has shown significant benefits in other organs and systems. Recent years have seen the demonstration of its cellular and vascular effects in animal models, potentially contributing to the reduction of reperfusion damage. However, no human studies have yet confirmed these effects.
Consequently, this double-blind, randomized, parallel-arm clinical trial was designed to evaluate the effect of empagliflozin treatment, administered from the pre-intervention period through to 3 days post-intervention, on the incidence of the no-reflow phenomenon in patients with ST-segment elevation myocardial infarction (STEMI) undergoing coronary angioplasty compared to a placebo.
Before entering the hemodynamics room, participants in the intervention group will receive a loading dose of 25 mg of empagliflozin or a placebo. In-hospital treatment will continue with 10 mg empagliflozin daily for 3 days for the intervention group, while the control group will receive a placebo. Patients will be monitored weekly during the first month and bi-weekly during the second and third months.
The primary outcome will be the incidence of the no-reflow phenomenon, measured through the Thrombolysis in Myocardial infarction (TIMI) flow scale in the coronary angiography performed to treat the infarction. Secondary outcomes will include the reduction of ST segment on the electrocardiogram, troponin levels, differences in the longitudinal strain by echocardiogram, and infarct size by magnetic resonance imaging.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Fabio Solis-Jimenez, MD, MSc
- Phone Number: +525540838443
- Email: fabiosolisjimenez@gmail.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Acute myocardial infarction with ST-segment elevation
- Presentation to the institute within 12 hours of symptom onset
- Coronary angioplasty chosen as the reperfusion treatment for the subject
- Informed consent signed
Exclusion Criteria:
- Hemodynamically unstable subjects
- Subjects undergoing thrombolysis treatment in the current event
- History of coronary revascularization surgery
- Known allergy or hypersensitivity to Sodium-glucose co-transporter-2 (SGLT2) inhibitors
- History of recurrent urinary tract infections
- Known chronic kidney disease and estimated glomerular filtration rate (eGFR) < 20
- Ongoing treatment with any SGLT2 inhibitor
- Participation in another clinical trial or having participated in the week prior to recruitment
- For women of childbearing age: Current or planned pregnancy or lactation.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Empagliflozin
The patients included in this group will receive a loading dose of 25 mg of Empagliflozin at the time of enrollment in the study, prior to percutaneous coronary intervention.
Over the following three days, they will receive a daily maintenance dose of 10 mg of Empagliflozin.
|
Load dose
Other Names:
Maintenance dose
Other Names:
|
Placebo Comparator: Placebo
The patients included in this group will receive a placebo (in an indistinguishable presentation from the active drug).
A loading dose of 25 mg of Placebo at the time of enrollment in the study, prior to percutaneous coronary intervention.
Over the following three days, they will receive a daily maintenance dose of 10 mg of Placebo.
|
Placebo for 25 dose
Other Names:
Placebo for 10mg dose
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Non-Reflow Phenomenon
Time Frame: During percutaneous coronary intervention (approximately 60 minutes after receiving the loading dose)
|
Incidence of non-reflow phenomenon during percutaneous coronary intervention measured using the Thrombolysis in myocardial infarction (TIMI) Flow Grading System. Dichotomous variable (yes/no). The TIMI flow grading system ranges from 0 to 3. Grade 3 flow is the best result of angioplasty and means that flow has been restored to normal. Grade 2 flow means that the contrast flows throughout the entire artery but more slowly than normal. Grade 1 flow means that the contrast flows through the artery but does not reach the end of the artery. Flow grade 0 means that contrast does not flow in the artery. It is the worst result of an angiography. Any flow other than grade 3 is interpreted as a non-reflow phenomenon. |
During percutaneous coronary intervention (approximately 60 minutes after receiving the loading dose)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Infract size
Time Frame: 72 hours after the loading dose
|
Myocardial infarct size measured in grams using cardiac magnetic resonance.
Continuous variable.
Mean difference between both groups.
This outcome will not be combined with other secondary outcomes.
|
72 hours after the loading dose
|
Longitudinal Strain
Time Frame: 24 hours after the loading dose
|
Longitudinal Strain measured in percentage using transthoracic echocardiogram.
Continuous variable.
Mean difference between both groups.
This outcome will not be combined with other secondary outcomes.
|
24 hours after the loading dose
|
High-sensitivity Troponin Clearance
Time Frame: 72 hours after the loading dose
|
Percentage of High-sensitivity troponin decrease when comparing admission values with values at 72 hours.
Continuous variable.
Mean difference between both groups.
This outcome will not be combined with other secondary outcomes.
|
72 hours after the loading dose
|
Creatine Kinase-myocardial band Clearance
Time Frame: 72 hours after the loading dose
|
Percentage of creatine kinase-myocardial band (CK-MB) decrease when comparing admission values with values at 72 hours.
Continuous variable.
Mean difference between both groups.
This outcome will not be combined with other secondary outcomes.
|
72 hours after the loading dose
|
Adverse Cardiovascular Events
Time Frame: Up to 3 months after the loading dose
|
Incidence of Rehospitalization, malignant arrhythmias, cardiogenic shock, reinfarction, urgent revascularization, death.
This outcome will not be combined with other secondary outcomes.
|
Up to 3 months after the loading dose
|
Collaborators and Investigators
Investigators
- Principal Investigator: Eduardo Arias-Sanchez, MD, Deputy Head of the Department of Interventional Cardiology at the National Institute of Cardiology
Publications and helpful links
General Publications
- Niccoli G, Burzotta F, Galiuto L, Crea F. Myocardial no-reflow in humans. J Am Coll Cardiol. 2009 Jul 21;54(4):281-92. doi: 10.1016/j.jacc.2009.03.054.
- Niccoli G, Kharbanda RK, Crea F, Banning AP. No-reflow: again prevention is better than treatment. Eur Heart J. 2010 Oct;31(20):2449-55. doi: 10.1093/eurheartj/ehq299. Epub 2010 Sep 13. No abstract available.
- Tasar O, Karabay AK, Oduncu V, Kirma C. Predictors and outcomes of no-reflow phenomenon in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Coron Artery Dis. 2019 Jun;30(4):270-276. doi: 10.1097/MCA.0000000000000726.
- Annibali G, Scrocca I, Aranzulla TC, Meliga E, Maiellaro F, Musumeci G. "No-Reflow" Phenomenon: A Contemporary Review. J Clin Med. 2022 Apr 16;11(8):2233. doi: 10.3390/jcm11082233.
- Sayour AA, Korkmaz-Icoz S, Loganathan S, Ruppert M, Sayour VN, Olah A, Benke K, Brune M, Benko R, Horvath EM, Karck M, Merkely B, Radovits T, Szabo G. Acute canagliflozin treatment protects against in vivo myocardial ischemia-reperfusion injury in non-diabetic male rats and enhances endothelium-dependent vasorelaxation. J Transl Med. 2019 Apr 16;17(1):127. doi: 10.1186/s12967-019-1881-8.
- Cooper S, Teoh H, Campeau MA, Verma S, Leask RL. Empagliflozin restores the integrity of the endothelial glycocalyx in vitro. Mol Cell Biochem. 2019 Sep;459(1-2):121-130. doi: 10.1007/s11010-019-03555-2. Epub 2019 May 24.
- Lahnwong C, Palee S, Apaijai N, Sriwichaiin S, Kerdphoo S, Jaiwongkam T, Chattipakorn SC, Chattipakorn N. Acute dapagliflozin administration exerts cardioprotective effects in rats with cardiac ischemia/reperfusion injury. Cardiovasc Diabetol. 2020 Jun 15;19(1):91. doi: 10.1186/s12933-020-01066-9.
- Shao Q, Meng L, Lee S, Tse G, Gong M, Zhang Z, Zhao J, Zhao Y, Li G, Liu T. Empagliflozin, a sodium glucose co-transporter-2 inhibitor, alleviates atrial remodeling and improves mitochondrial function in high-fat diet/streptozotocin-induced diabetic rats. Cardiovasc Diabetol. 2019 Nov 28;18(1):165. doi: 10.1186/s12933-019-0964-4.
- Kolijn D, Pabel S, Tian Y, Lodi M, Herwig M, Carrizzo A, Zhazykbayeva S, Kovacs A, Fulop GA, Falcao-Pires I, Reusch PH, Linthout SV, Papp Z, van Heerebeek L, Vecchione C, Maier LS, Ciccarelli M, Tschope C, Mugge A, Bagi Z, Sossalla S, Hamdani N. Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Galpha oxidation. Cardiovasc Res. 2021 Jan 21;117(2):495-507. doi: 10.1093/cvr/cvaa123.
- Lu Q, Liu J, Li X, Sun X, Zhang J, Ren D, Tong N, Li J. Empagliflozin attenuates ischemia and reperfusion injury through LKB1/AMPK signaling pathway. Mol Cell Endocrinol. 2020 Feb 5;501:110642. doi: 10.1016/j.mce.2019.110642. Epub 2019 Nov 21.
- Tan Y, Yu K, Liang L, Liu Y, Song F, Ge Q, Fang X, Yu T, Huang Z, Jiang L, Wang P. Sodium-Glucose Co-Transporter 2 Inhibition With Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism. Front Pharmacol. 2021 Oct 12;12:758080. doi: 10.3389/fphar.2021.758080. eCollection 2021.
- Uthman L, Li X, Baartscheer A, Schumacher CA, Baumgart P, Hermanides J, Preckel B, Hollmann MW, Coronel R, Zuurbier CJ, Weber NC. Empagliflozin reduces oxidative stress through inhibition of the novel inflammation/NHE/[Na+]c/ROS-pathway in human endothelial cells. Biomed Pharmacother. 2022 Feb;146:112515. doi: 10.1016/j.biopha.2021.112515. Epub 2021 Dec 9.
- Seo MS, Jung HS, An JR, Kang M, Heo R, Li H, Han ET, Yang SR, Cho EH, Bae YM, Park WS. Empagliflozin dilates the rabbit aorta by activating PKG and voltage-dependent K+ channels. Toxicol Appl Pharmacol. 2020 Sep 15;403:115153. doi: 10.1016/j.taap.2020.115153. Epub 2020 Jul 24.
- Zou R, Shi W, Qiu J, Zhou N, Du N, Zhou H, Chen X, Ma L. Empagliflozin attenuates cardiac microvascular ischemia/reperfusion injury through improving mitochondrial homeostasis. Cardiovasc Diabetol. 2022 Jun 15;21(1):106. doi: 10.1186/s12933-022-01532-6.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 24-1423
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on STEMI
-
Clinical Operations WCN B.V.SanofiEnrolling by invitationAtherosclerotic Cardiovascular Disease | STEMI | Non STEMINetherlands
-
Kingston UniversityUniversity of Leeds; Swansea University; London Ambulance Service; West Midlands... and other collaboratorsCompletedAcute Coronary Syndrome | STEMI | Non STEMIUnited Kingdom
-
Karolinska InstitutetEnrolling by invitation
-
Beijing Friendship HospitalActive, not recruiting
-
University of OradeaCompleted
-
Prolocor, IncActive, not recruitingSTEMI | NSTEMIUnited States
-
Assistance Publique - Hôpitaux de ParisCompletedPrimary PCI - STEMIFrance
-
VesalioRecruitingSegment Elevation Myocardial Infarction (STEMI)Switzerland
-
University of PisaCompleted
-
AstraZenecaCompletedMyocardial Infarction | Segment Elevation Myocardial Infarction (STEMI)Australia, France, Italy, Spain, United Kingdom, Sweden, Germany, Hungary, Denmark, Austria, Canada, Netherlands, Algeria
Clinical Trials on Empagliflozin 25 milgrams (Mg)
-
National Taiwan University HospitalShin Kong Wu Ho-Su Memorial HospitalNot yet recruitingHeart Failure With Preserved Ejection Fraction | End Stage Renal Disease on Dialysis
-
University of Sao Paulo General HospitalRecruitingCoronary Artery Disease | Diabetes Mellitus, Type 2 | Acute Kidney Injury | Coronary Artery Bypass SurgeryBrazil
-
Boehringer IngelheimEli Lilly and CompanyCompletedDiabetes Mellitus, Type 2Japan
-
Amsterdam UMC, location VUmcCompleted
-
Yale UniversityBoehringer IngelheimRecruitingEnd Stage Renal Disease on DialysisUnited States
-
University of Mississippi Medical CenterEli Lilly and CompanyRecruiting
-
University Health Network, TorontoRecruiting
-
Tanta UniversityActive, not recruiting
-
Isfahan University of Medical SciencesCompletedDiabetes MellitusIran, Islamic Republic of
-
The University of Texas Health Science Center at...National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Doris...RecruitingType2 Diabetes | Heart Failure With Preserved Ejection FractionUnited States