Effect of Nicorandil for the Patients of Acute ST Segment Elevation Myocardial Infarction

Coronary Heart Disease Clinical Trial

Official title:

Effect of Early Administration of Intracoronary Nicorandil Via Thrombus Aspiration Catheter Device During Primary Percutaneous Coronary Intervention for the Patients of Acute ST Segment Elevation Myocardial Infarction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02435797
• Other study ID #: W201416
• Status: Recruiting
• Phase: Phase 4
• First received: April 23, 2015
• Last updated: May 5, 2015
• Start date: April 2015
• Est. completion date: October 2016

Study information

• Verified date: May 2015
• Source: Xuzhou Central Hospital
• Contact: Feng chunguang, PhD
• Phone: +8618936376559
• Email: fcg999[@]163.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To evaluate whether nicorandil as an adjunctive therapy for acute myocardial infarction (AMI) reduces reperfusion injury.

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 myocardial cellular apoptosis, 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 and left ventricle remodeling 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.So,it could decrease the phenomenon of no-reflow/slow reflow,reperfusion-induced arrhythmia and worsening of chest pain.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: October 2016
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

• Acute ST Segment Elevation Myocardial Infarction (ASTEMI) defined as typical chest pain lasting >30min within the previous 12 h, with a clear ST-segment elevation of >0.1millivolt(mV) in =2 contiguous electrocardiographic leads, and the value of troponin I(TNI) above the maximum peak in the normal range.

• Age20-80,All genders

• The first myocardial infarction, and there is no history of PCI therapy and coronary artery bypass grafting

• The infarct-related artery(IRA) is totally occlusive

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

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

• Successful interventional treatment, the residual stenosis of IRA is less than 30% ,

• TIMI flow grade 3

Exclusion Criteria:

• kidney dysfunction (creatinine >2 mg/dl),

• History of previous liver disease,

• Cardiogenic shock,

• History of myocardial infarction (MI)

• History of coronary artery bypass grafting

• History of allergic response to drugs

• Right ventricular infarction

• Severe hypovolemia

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Infarction
• Myocardial Infarction
• Myocardial Ischemia

Intervention

Drug:
• Nicorandil
All patients received antiplatelet agents (aspirin, ticagrelor) and heparin.Diagnostic coronary angiography (CAG) was performed via the right (or left) femoral artery or radial artery using the Seldinger method.The guidewire was passed into the culprit lesion. Subjects in the NicorandilGroup were then given 2 mg intracoronary nicorandil through the lesions via thrombus aspiration catheter, and an additional intracoronary dose of 2 mg nicorandil before stent implantation. A minimum 5-min interval occurred between the first and second doses of nicorandil to reduce adverse effects.
• normal saline
All patients received antiplatelet agents (aspirin, ticagrelor) and heparin.Diagnostic coronary angiography (CAG) was performed via the right (or left) femoral artery or radial artery using the Seldinger method.The guidewire was passed into the culprit lesion. Normal saline in the Placebo Group were then given 2 ml through the lesions via thrombus aspiration catheter,and an additional intracoronary dose of 2 ml before stent implantation. A minimum 5-min interval occurred between the first and second injection.

Locations

Country	Name	City	State
China	Xuzhou Central Hospital	Xuzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Xuzhou Central Hospital

Country where clinical trial is conducted

China, 

References & Publications (13)

Costantini CO, Stone GW, Mehran R, Aymong E, Grines CL, Cox DA, Stuckey T, Turco M, Gersh BJ, Tcheng JE, Garcia E, Griffin JJ, Guagliumi G, Leon MB, Lansky AJ. Frequency, correlates, and clinical implications of myocardial perfusion after primary angioplasty and stenting, with and without glycoprotein IIb/IIIa inhibition, in acute myocardial infarction. J Am Coll Cardiol. 2004 Jul 21;44(2):305-12. — View Citation

De Luca G, Navarese EP, Suryapranata H. A meta-analytic overview of thrombectomy during primary angioplasty. Int J Cardiol. 2013 Jul 1;166(3):606-12. doi: 10.1016/j.ijcard.2011.11.102. Epub 2012 Jan 28. Review. — View Citation

Kitakaze M, Asakura M, Kim J, Shintani Y, Asanuma H, Hamasaki T, Seguchi O, Myoishi M, Minamino T, Ohara T, Nagai Y, Nanto S, Watanabe K, Fukuzawa S, Hirayama A, Nakamura N, Kimura K, Fujii K, Ishihara M, Saito Y, Tomoike H, Kitamura S; J-WIND investigators. Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials. Lancet. 2007 Oct 27;370(9597):1483-93. Erratum in: Lancet. 2008 Dec 22;370(9605):2102. — View Citation

Lim SY, Bae EH, Jeong MH, Kang DG, Lee YS, Kim KH, Lee SH, Yoon KH, Hong SN, Park HW, Hong YJ, Kim JH, Kim W, Ahn YK, Cho JG, Park JC, Kang JC. Effect of combined intracoronary adenosine and nicorandil on no-reflow phenomenon during percutaneous coronary intervention. Circ J. 2004 Oct;68(10):928-32. — View Citation

Limbruno U, De Carlo M, Pistolesi S, Micheli A, Petronio AS, Camacci T, Fontanini G, Balbarini A, Mariani M, De Caterina R. Distal embolization during primary angioplasty: histopathologic features and predictability. Am Heart J. 2005 Jul;150(1):102-8. — View Citation

Marzilli M, Orsini E, Marraccini P, Testa R. Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation. 2000 May 9;101(18):2154-9. — View Citation

Moens AL, Claeys MJ, Timmermans JP, Vrints CJ. Myocardial ischemia/reperfusion-injury, a clinical view on a complex pathophysiological process. Int J Cardiol. 2005 Apr 20;100(2):179-90. Review. — View Citation

Ota S, Nishikawa H, Takeuchi M, Nakajima K, Nakamura T, Okamoto S, Setsuda M, Makino K, Yamakado T, Nakano T. Impact of nicorandil to prevent reperfusion injury in patients with acute myocardial infarction: Sigmart Multicenter Angioplasty Revascularization Trial (SMART). Circ J. 2006 Sep;70(9):1099-104. — View Citation

Reffelmann T, Kloner RA. The "no-reflow" phenomenon: basic science and clinical correlates. Heart. 2002 Feb;87(2):162-8. Review. — View Citation

Taira N. Nicorandil as a hybrid between nitrates and potassium channel activators. Am J Cardiol. 1989 Jun 20;63(21):18J-24J. Review. — View Citation

Tanaka A, Kawarabayashi T, Nishibori Y, Sano T, Nishida Y, Fukuda D, Shimada K, Yoshikawa J. No-reflow phenomenon and lesion morphology in patients with acute myocardial infarction. Circulation. 2002 May 7;105(18):2148-52. — View Citation

Tsubokawa A, Ueda K, Sakamoto H, Iwase T, Tamaki S. Effect of intracoronary nicorandil administration on preventing no-reflow/slow flow phenomenon during rotational atherectomy. Circ J. 2002 Dec;66(12):1119-23. — View Citation

Werner GS, Lang K, Kuehnert H, Figulla HR. Intracoronary verapamil for reversal of no-reflow during coronary angioplasty for acute myocardial infarction. Catheter Cardiovasc Interv. 2002 Dec;57(4):444-51. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary composite endpoint (whether premature beats,atrial or ventricular tachycardia, atrial or ventricular fibrillation, and atrioventricular block appears;whether severity of chest pain is aggravated,and number of episodes chest pain)	The primary composite endpoint consisted of reperfusion-induced arrhythmia, worsening of chest pain, and no-reflow/slow reflow.; In perioperative period,we will observe whether the reperfusion-induced arrhythmia including atrial or ventricular premature beats,atrial or ventricular tachycardia, atrial or ventricular fibrillation, and atrioventricular block appears;whether the severity of chest pain is aggravated,and the number of episodes of chest pain will be recorded for patients who complains of chest pain that lasted for at least 30 min within the 24 h following onset of MI;Whether the phenomenon of no-reflow/slow reflow appears.No-reflow and slow flow are diagnosed when the thrombolysis in myocardial infarction(TIMI) flow grade is 2 or lower,despite successful PCI such as balloon angioplasty or stent insertion.	24hours	Yes
Secondary	the combined outcome of TIMI frame count (cTFC) of CAG and ST resolution (STR) of ECG	The cTFC was measured according to the method of Gibson et al, to determine blood flow at the time of coronary angiography. The cine frame counts derived from the injection of contrast medium to the peripheral landmark were measured .; In order to evaluate STR, the total sum of the ST segments elevation from the J point to the point reached 20ms later was calculated from the 12-lead ECG recorded before the start of reperfusion, and 90 min after the completion of reperfusion. The rate of improvement in ST elevation was classified as "complete resolution" (70% or more improvement) and "no resolution" (<70%).	24hours	Yes