Effect of Nicorandil on Cardiac Sympathetic Nerve for the Patients of Acute ST Segment Elevation Myocardial Infarction

Coronary Heart Disease Clinical Trial

Official title:

Effects of Nicorandil on Cardiac Sympathetic Nerve Activity and Distribution in Patients With Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04826497
• Other study ID #: 2021KC20122
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: April 2021
• Est. completion date: February 2022

Study information

• Verified date: March 2021
• Source: Xuzhou Central Hospital
• Contact: chunguang Feng, PhD
• Phone: +8618936376559
• Email: fcg999[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators evaluate the effects of intracoronary and intravenous administration of nicorandil on cardiac sympathetic nerve activity and distribution in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention

Description:

Reperfusion injury might occur in patients with acute ST segment elevation myocardial infarction undergoing the primary percutaneous coronary intervention(P-PCI),characterized by myocardial stunning, reperfusion-induced arrhythmia, microvascular dysfunction and injury of cardiac sympathetic nerve, etc.

Nicorandil is an antianginal agent with a dual mechanism of action: nitrate and K+ATP channel opener. The nitrate action causes vasodilation of systemic veins and epicardial coronary arteries, while the adenosine triphosphate (ATP)-sensitive potassium channel opener action causes vasodilation of peripheral and coronary resistance arterioles. Nicorandil not only decreases preload and afterload but also increases coronary blood flow.

The study will compare the effectiveness between nicorandil and placebo of preventing the reperfusion injury especially injury of cardiac sympathetic nerve in patients with acute ST segment elevation myocardial infarction undergoing the P-PCI.It is intended that before reperfusion injury ,nicorandil which was early used by intracoronary injection could prevent and release the microcirculatory spasm, release the coronary microvascular endothelial swelling,decrease embolism of atherosclerotic debris and thrombus formation,moreover,it could reduces the release of norepinephrine from sympathetic endings of the heart directly.So,it could decrease the phenomenon of no-reflow/slow reflow,reperfusion-induced arrhythmia and injury of cardiac sympathetic nerve.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: February 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

1. acute ST-segment elevation myocardial infarction within 12 hours of symptom onset;

2. Age20-80,All genders

3. anterior myocardial infarction

4. The first myocardial infarction

5. The infarct-related artery(IRA) is totally occlusive

6. Blood pressure is higher than 90/60 millimeters of mercury(mmHg)

7. The time from myocardial infarction onset to reach the hospital is less than 12 hs

Exclusion Criteria:

1. kidney dysfunction (creatinine >2 mg/dl),

2. History of previous liver disease,

3. Cardiogenic shock,

4. History of myocardial infarction (MI)

5. History of coronary artery bypass grafting

6. History of allergic response to drugs

7. Severe hypovolemia

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Infarction
• Myocardial Infarction
• Myocardial Ischemia
• ST Elevation Myocardial Infarction

Intervention

Drug:
• nicorandil
All patients received antiplatelet agents (aspirin, ticagrelor) and heparin.Diagnostic coronary angiography (CAG) was performed via the radial artery using the Seldinger method.The guidewire was passed into the culprit lesion.If the blood flow of culprit vessel reaches TIMI2-3 after balloon dilatation,6mg nicorandil was then administrated before stent implantation, A minimum 5-min interval occurred between the first and second doses of nicorandil to reduce adverse effects, subsequently , 6mg/h ivgtt. up to 48h after coronary intervention
• Placebo(normal saline)
All patients received antiplatelet agents (aspirin, ticagrelor) and heparin.Diagnostic coronary angiography (CAG) was performed via the radial artery using the Seldinger method.The guidewire was passed into the culprit lesion.If the blood flow of culprit vessel reaches TIMI2-3 after balloon dilatation,6mg placebo was then administrated before stent implantation, A minimum 5-min interval occurred between the first and second doses of placebo to reduce adverse effects, subsequently , 6mg/h ivgtt. up to 48h after coronary intervention

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Xuzhou Central Hospital

References & Publications (7)

Fukui Y, Nozawa T, Ihori H, Sobajima M, Nakadate T, Matsuki A, Nonomura M, Fujii N, Inoue H, Kinugawa K. Nicorandil Attenuates Ischemia-Reperfusion Injury Via Inhibition of Norepinephrine Release From Cardiac Sympathetic Nerve Terminals. Int Heart J. 2017 — View Citation

Hicks KA, Mahaffey KW, Mehran R, Nissen SE, Wiviott SD, Dunn B, Solomon SD, Marler JR, Teerlink JR, Farb A, Morrow DA, Targum SL, Sila CA, Thanh Hai MT, Jaff MR, Joffe HV, Cutlip DE, Desai AS, Lewis EF, Gibson CM, Landray MJ, Lincoff AM, White CJ, Brooks — View Citation

Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P; ESC Scientific Document Gr — View Citation

Ji Z, Zhang R, Lu W, Ma G, Qu Y. The effect of nicorandil in patients with acute myocardial infarction undergoing percutaneous coronary intervention: a systematic review and meta-analysis. Ir J Med Sci. 2020 Feb;189(1):119-131. doi: 10.1007/s11845-019-020 — View Citation

Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, Kurabayashi M. Effects of nicorandil on cardiac sympathetic nerve activity after reperfusion therapy in patients with first anterior acute myocardial infarction. Eur J Nucl Med Mol Imaging. — View Citation

Piper HM, Meuter K, Schäfer C. Cellular mechanisms of ischemia-reperfusion injury. Ann Thorac Surg. 2003 Feb;75(2):S644-8. Review. — View Citation

Xu L, Wang L, Li K, Zhang Z, Sun H, Yang X. Nicorandil prior to primary percutaneous coronary intervention improves clinical outcomes in patients with acute myocardial infarction: a meta-analysis of randomized controlled trials. Drug Des Devel Ther. 2019 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of the delayed heart/mediastinum count (H/M) ratio	The delayed heart/mediastinum count (H/M) ratio was determined from 123I-meta-iodobenzylguanidine (MIBG) images	10 days after primary PCI
Secondary	The total defect score (TDS)	The total defect score was determined from 123I-meta-iodobenzylguanidine (MIBG) images	10 days after primary PCI
Secondary	Rate of slow re-flow/no-reflow phenomenon	TIMI myocardial perfusion grade (TMPG) of the final coronary flow in the culprit artery	5 minutes after primary PCI
Secondary	Rate fo complete ST-segment resolution	ST-segment resolution >50 percent in ECG	2 hours after primary PCI
Secondary	Rate of unplanned hospitalization for heart failure	Rate of unplanned hospitalization for heart failure	6 months after primary PCI
Secondary	The washout rate (WR)	The washout rate (WR) were determined from 123I-meta-iodobenzylguanidine (MIBG) images	10 days after primary PCI
Secondary	The total defect score (TDS)	The total defect score was determined from 99mTc-pyrophosphate scintigraphy	7 days after primary PCI