Oral Nicorandil in ST Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

• Conditions: Nicorandil
• Interventions: Drug: Nicorandil 20 MG

• Registration Number: NCT04632121
• Lead Sponsor: Ahmed Abdel Nasser Abdel Rady

Brief Summary

* To study the effects of early oral administration of nicorandil in the setting of PPCI among STEMI patients on early angiographic, electrocardiographic, echocardiographic and hard clinical outcomes.

* To assess the possible benefits of nicorandil on myocardial reperfusion through LGE- CMR substudy after 3 months.

Detailed Description

Nicorandil is a nicotinamide ester that dilates peripheral and coronary resistance vessels via action on ATP-sensitive potassium channels and possesses a nitrate moiety that promotes systemic venous and coronary vasodilation. As a result of these dual actions, nicorandil reduces preload and afterload and results in an increase in coronary blood flow. In addition to these effects, nicorandil may have cardioprotective actions mediated through the activation of potassium channel .

Previous study on the effect of nicorandil on patients with stable angina has shown significant improvement in outcome due to a reduction in major coronary events.

Acute occlusion of the coronary artery in the STEMI patient subjects the myocardium supplied by that vessel to acute myocardial ischemia, thereby demarcating the area at risk (AAR) of potential MI, should the acute coronary occlusion be sustained or permanent. If the period of acute myocardial ischemia is prolonged (more than 20 minutes) a "wave front" of cardiomyocyte death begins in the subendocardium and extends transmurally over time toward the epicardium.

The deprivation of oxygen and nutrient supply results in a series of abrupt biochemical and metabolic changes within the myocardium. The absence of oxygen halts oxidative phosphorylation, leading to mitochondrial membrane depolarization, ATP depletion, and inhibition of myocardial contractile function.

Ischemia-Reperfusion injury (IRI) is defined as the paradoxical exacerbation of cellular dysfunction and death, following restoration of blood flow to previously ischemic tissues. Reestablishment of blood flow is essential to salvage ischemic tissues. However reperfusion itself paradoxically causes further damage, threatening function and viability of the organ.

Early intra-coronary administration of nicorandil has been shown to reduce the damage in the myocardial microcirculation caused by PPCI and the myocardial infarct size in patients with AMI .

Nicorandil prior to reperfusion was suggested to improve coronary flow. Furthermore, suppression of ventricular arrhythmia, and improvement of left ventricular function were demonstrated in patients who suffered from AMI and underwent primary PCI. But the definite clinical benefits of nicorandil were not found, which may be due to the small sample size of the selected studies .

Compared with intracoronary use alone, the intracoronary and peripheral intravenous use of nicorandil can better improve myocardial microcirculation and short-term prognosis .

Nicorandil use prior and post PCI could decrease the occurrence rate of ventricular arrhythmia in STEMI patients undergoing emergent PCI, and this effect might be related with reduced QTd and QTcd post medication .

Whether oral nicorandil, which is more widely available and more affordable, would have clinical benefits in terms of measures of reperfusion, and LV recovery post-STEMI, when administered in the early phase of STEMI is still questionable, and warrants further research.

Study Timeline

• Study First Submitted: 2020-10-31
• Study First Submitted QC: 2020-11-11
• Study First Posted: 2020-11-17
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-02
• Last Update Posted: 2021-01-05
• Study Start: 2021-04-01
• Primary Completion: 2022-12-01
• Study Completion: 2023-12-29

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Patients with STEMI eligible for PPCI.

Exclusion Criteria

• Patients undergoing other reperfusion strategies, including fibrinolysis, rescue PCI or pharmacoinvasive PCI.
• Patients presenting with Cardiogenic shock or symptomatic hypotension (BP< 90/60 mmHg)
• Patients who have contraindications for nicorandil e.g. advanced hepatic disease.
• Patients not consenting to the study protocol.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Group A	Nicorandil 20 MG	will receive standard treatment + 20 mg nicorandil prior to PPCI, and then maintained on 20 mg b.i.d for 3 months .

Primary Outcome Measures

Name	Time	Method
Angiographic evidence of epicardial successful reperfusion	1 day around PCI	Angiographic evidence of epicardil successful reperfusion including; TIMI flow grade, and TIMI frame count.
Angiographic evidence of tissue-level successful reperfusion	1 day around PCI	Angiographic evidence of tissue-level successful reperfusion (Myocardial blush grade).

Secondary Outcome Measures

Name	Time	Method
Electrocardiographic measures of repolarization dispersion	after 90 minutes of PPCI	Electrocardiographic measures of repolarization dispersion including; QTc, QTD, T-peak to T-end interval (Tp-Te), and its dispersion, and Tp-Te/QT ratio, as well as ST segment resolution at 90 minutes from reperfusion.
Echocardiographic measures of LV recovery	before discharge and at 3 months after index event.	Echocardiographic measures of LV recovery including; 2-D left ventricular ejection fraction, left ventricle volumes, Mitral regurge severity, and wall motion score index.
Speckle tracking for global longitudinal strain of left ventricle	before discharge and at 3 months after index event	2D- Left ventricle Global longitudinal strain by speckle tracking echocardiography (only 50 patients in each group)