Empagliflozin for No-reflow Phenomenon in PCI for STEMI

STEMI Clinical Trial

— EMPA-PCI  

Official title:

Empagliflozin for Reducing the Risk of No-Reflow Phenomenon in Patients Undergoing Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06342141
• Other study ID #: 24-1423
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 15, 2024
• Est. completion date: March 15, 2025

Study information

• Verified date: March 2024
• Source: Instituto Nacional de Cardiologia Ignacio Chavez
• Contact: Fabio Solis-Jimenez, MD, MSc
• Phone: +525540838443
• Email: fabiosolisjimenez[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 162
• Est. completion date: March 15, 2025
• Est. primary completion date: January 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• No-Reflow Phenomenon
• STEMI

Intervention

Drug:
• Empagliflozin 25 milgrams (Mg)
Load dose
• Empagliflozin 10 Mg
Maintenance dose
• Placebo 25 Mg
Placebo for 25 dose
• Placebo 10 Mg
Placebo for 10mg dose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Cardiologia Ignacio Chavez

References & Publications (14)

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. — View Citation

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. — View Citation

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. Empaglifl — View Citation

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 — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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-dia — View Citation

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.2020.115 — View Citation

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. — View Citation

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 Pha — View Citation

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. — View Citation

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 endotheli — View Citation

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Non-Reflow Phenomenon	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	Infract size	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
Secondary	Longitudinal Strain	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
Secondary	High-sensitivity Troponin Clearance	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
Secondary	Creatine Kinase-myocardial band Clearance	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
Secondary	Adverse Cardiovascular Events	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