China-Administration of Nicorandil Group（CHANGE）

Effects of Nicorandil on Cardiac Infarct Size in Patients With ST-segment Elevation Acute Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

We compared the infarct size in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) treated by nicorandil before and after the reperfusion with those standard therapy treated by PCI

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Percutaneous Coronary Intervention; Nicorandil
• Intervention / Treatment: Drug: Nicorandil; Other: Placebo

Detailed Description

The aim of this study was to evaluate the efficacy and safety of nicorandil in improving myocardial infarct size in patients with acute myocardial infarction through a multi-center, prospective, randomized, double-blind and parallel-controlled clinical study, providing evidence-based support for the optimization of PCI treatment strategies. The primary objective of the study was to compare whether the effect of nicorandil in combination with PCI was significantly better at reducing the myocardial infarct size than that of PCI alone in AMI patients.

• Study Type: Interventional
• Enrollment (Actual): 238
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Acute ST-T elevation MI patients (<12h)
2. undergoing emergency PCI；
3. Subject has read and signed a written, informed consent form.

Exclusion Criteria:

1. SBP<80mmHg；
2. LM stenosis
3. Aortic dissection；
4. AMI (<6 month)
5. PCI或CABG (<6 month)
6. Already under the treatment of Nicorandil；
7. Contraindicated or intolerable to Nicorandil
8. severe adverse effects to CMR or MRI；
9. Currently (or within one month) participating in another new drug trial.；
10. Pregnant or lactation period；
11. Severe somatic disease preventing the participant from completing the trial, or based on the discretion of the investigators, the patient is incapable of participating; Individuals with abnormal laboratory test results and/or clinical manifestations rendering them unsuitable to participate as judged by the investigators;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment arm; Patients were randomly assigned to two groups before emergent coronary angiography: those who received intravenous (iv.) nicorandil before and after (ivgtt.) reperfusion with PCI (nicorandil group);	Drug: Nicorandil; After randomization, receive primary PCI and standard therapy, 12mg Nicorandil iv. just before ballooning or stenting, then keep Nicorandil 6mg/h ivgtt. up to 24h
PLACEBO_COMPARATOR: Placebo arm; Patients were randomly assigned to two groups before emergent coronary angiography, those who received placebo before and after reperfusion with PCI.	Other: Placebo; After randomization, receive primary PCI and standard therapy, just like the intervension group also iv. just before ballooning or stenting, then keep ivgtt. up to 24h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infarct size as measured by cardiac MRI	The myocardial infarct size was derived by measuring the area of delay-enhanced image-enhanced MRI, which was judged and analyzed by two experienced MRI cardiac diagnosticians.	7 days after primary PCI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infarct size as measured by cardiac MRI	The myocardial infarct size was derived from the program's automatic analysis of delayed enhancement images.	6 months after PCI
Corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC)	the starting point is the number of frames in which the contrast agent completely or nearly completely filled the beginning of the coronary artery and touched both sides of the coronary vessel wall, and the end point is the number of frames in which the contrast agent entered the distal branch vessel and developed a specific anatomical marker	5 minutes after stent implantation during PCI
Incidence of slow flow/no-reflow	When scanning at a rate of 15 frames per second, cTFC > 27 frames per second was used as the criterion for the diagnosis of slow blood flow after primary PCI	5 minutes after stent implantation during PCI
ST-segment fall rate of electrocardiogram (ECG)	Complete ST-segment resolution at 2 h after PCI	2 hours after the procedure
Serum creatinine kinase (CK-MB) level	Change of serum creatinine kinase	Baseline, 6, 12, 18, 24 hours after the PCI
Edema size (LV area %) measured by cardiac MRI	Edema size	7 days after the procedure
Microvascular obstructionmeasured by cardiac MRI	Microvascular obstructionmeasured	7 days after the procedure
LV Ejection fraction (%) as measured by cardiac MRI	LV Ejection fraction in early phase	7 days after the procedure
LV Ejection fraction (%) as measured by cardiac MRI	LV Ejection fraction in late phase	6 months after the procedure
MACE	all-cause death, cardiovascular death, , Rehospitalization for heart failure, Unplanned PCI After PPCI	up to 12 months
CIN	contrast induced nephropathy	48-72 hours after primary PCI

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Collaborators: The Second Hospital of Hebei Medical University; Beijing Chao Yang Hospital; Guizhou Provincial People's Hospital; Wuhan Asia Heart Hospital; Second Affiliated Hospital of Nanchang University; Zunyi Medical College; First People's Hospital of Yulin; Hainan Hospital of PLA General Hospital

Publications and helpful links

General Publications

• Ishii H, Ichimiya S, Kanashiro M, Amano T, Imai K, Murohara T, Matsubara T. Impact of a single intravenous administration of nicorandil before reperfusion in patients with ST-segment-elevation myocardial infarction. Circulation. 2005 Aug 30;112(9):1284-8. doi: 10.1161/CIRCULATIONAHA.104.530329. Epub 2005 Aug 22.
• Ito H, Taniyama Y, Iwakura K, Nishikawa N, Masuyama T, Kuzuya T, Hori M, Higashino Y, Fujii K, Minamino T. Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J Am Coll Cardiol. 1999 Mar;33(3):654-60. doi: 10.1016/s0735-1097(98)00604-4.
• 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. doi: 10.1016/S0140-6736(07)61634-1. Erratum In: Lancet. 2008 Dec 22;370(9605):2102.
• Bulluck H, Hammond-Haley M, Weinmann S, Martinez-Macias R, Hausenloy DJ. Myocardial Infarct Size by CMR in Clinical Cardioprotection Studies: Insights From Randomized Controlled Trials. JACC Cardiovasc Imaging. 2017 Mar;10(3):230-240. doi: 10.1016/j.jcmg.2017.01.008.
• Ishii H, Ichimiya S, Kanashiro M, Amano T, Ogawa Y, Mitsuhashi H, Sakai S, Uetani T, Murakami R, Naruse K, Murohara T, Matsubara T. Effect of intravenous nicorandil and preexisting angina pectoris on short- and long-term outcomes in patients with a first ST-segment elevation acute myocardial infarction. Am J Cardiol. 2007 May 1;99(9):1203-7. doi: 10.1016/j.amjcard.2006.12.034. Epub 2007 Mar 16.
• IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial. Lancet. 2002 Apr 13;359(9314):1269-75. doi: 10.1016/S0140-6736(02)08265-X. Erratum In: Lancet 2002 Sep 7;360(9335):806.
• Okamura A, Rakugi H, Ohishi M, Yanagitani Y, Shimizu M, Nishii T, Taniyama Y, Asai T, Takiuchi S, Moriguchi K, Ohkuro M, Komai N, Yamada K, Inamoto N, Otsuka A, Higaki J, Ogihara T. Additive effects of nicorandil on coronary blood flow during continuous administration of nitroglycerin. J Am Coll Cardiol. 2001 Mar 1;37(3):719-25. doi: 10.1016/s0735-1097(00)01171-2.
• Kostic J, Djordjevic-Dikic A, Dobric M, Milasinovic D, Nedeljkovic M, Stojkovic S, Stepanovic J, Tesic M, Trifunovic Z, Zamaklar-Tifunovic D, Radosavljevic-Radovanovic M, Ostojic M, Beleslin B. The effects of nicorandil on microvascular function in patients with ST segment elevation myocardial infarction undergoing primary PCI. Cardiovasc Ultrasound. 2015 May 27;13:26. doi: 10.1186/s12947-015-0020-9.
• Qian G, Zhang Y, Dong W, Jiang ZC, Li T, Cheng LQ, Zou YT, Jiang XS, Zhou H, A X, Li P, Chen ML, Su X, Tian JW, Shi B, Li ZZ, Wu YQ, Li YJ, Chen YD. Effects of Nicorandil Administration on Infarct Size in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: The CHANGE Trial. J Am Heart Assoc. 2022 Sep 20;11(18):e026232. doi: 10.1161/JAHA.122.026232. Epub 2022 Sep 8.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 24, 2018
• Primary Completion (ACTUAL): July 31, 2020
• Study Completion (ACTUAL): October 1, 2021

Study Registration Dates

• First Submitted: February 2, 2018
• First Submitted That Met QC Criteria: February 20, 2018
• First Posted (ACTUAL): February 26, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 24, 2021
• Last Update Submitted That Met QC Criteria: November 18, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Cardiac magnetic resonance; Infarct Size
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Micronutrients; Vitamins; Vitamin B Complex; Nicorandil
• Other Study ID Numbers: CHANGE 001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No