Efficacy Study of Nicorandil on Neointima

Diabetes Mellitus Clinical Trial

Official title:

Efficacy Study of Nicorandil on Neointima After Coronary Drug-eluting Stent Implantation in Patients With Diabetic Mellitus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02328521
• Other study ID #: S2014-099-03
• Secondary ID: S2014-120-01
• Status: Recruiting
• Phase: Phase 4
• First received: December 24, 2014
• Last updated: January 17, 2015
• Start date: December 2014
• Est. completion date: July 2016

Study information

• Verified date: January 2015
• Source: Chinese PLA General Hospital
• Contact: Ying Qian Zhang, M.D.
• Phone: 86-15652505966
• Email: niniya731[@]163.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The investigators aim to investigate the effect of oral nicorandil on neointima after coronary drug-eluting stent implantation in patients with diabetic mellitus.

Description:

In the era of bare metal stent (BMS), the restenosis rate was about 25%. The introduction of drug-eluting stent (DES) reduces restenosis rate to 4%-10%. Neointimal hyperplasia and restenosis remain to be problems after DES implantation. Besides, DES causes an increase in uncovered struts, late stent thrombosis, neoatherosclerosis, and heterogeneous neointima. Diabetes mellitus (DM) results in increased risk for atherosclerosis, in-stent restenosis, neoatherosclerosis and late-stent thrombosis. Nicorandil, a hybrid of adenosine triphosphate-sensitive potassium (K-ATP) channel opener and nitrates, has been shown to reduce target vessel revascularization after stent implantation, target lesion revascularization after rotational atherectomy, and restenosis in patients undergoing percutaneous coronary intervention (PCI). Intracoronary optical coherence tomography(OCT) has emerged as a high-resolution imaging method for analysis of neointima that grows over the stent. We aim to examine the effect of nicorandil on the neointima after coronary DES implantation in patients with unstable angina and DM.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: July 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• unstable angina with diabetes mellitus and is not given glibenclamide

• have clinical indication of percutaneous coronary intervention

• de novo severe stenosis in a native coronary artery

• lesion suitable for stent and optical coherence tomography examination

• reference vessel size between 2.5 and 4.0mm

• drug-eluting stent implantation only

Exclusion Criteria:

• acute myocardial infarction within 2 weeks before percutaneous coronary intervention

• contraindications to treatment with nicorandil (allergy, glaucoma, digestive ulcer, is currently taking phosphodiesterase-5 inhibitor)

• bypass restenosis

• PCI history

• hypotension

• intolerance of platelet inhibitors and statins

• impaired liver function

• renal insufficiency requiring hemodialysis

• pregnancy

• connective tissue disease

• life expectancy = 12 months

• left main coronary artery disease

• bypass graft lesion and lesions unsuitable for OCT

• unwillingness or inability to provide informed consent

Study Design

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

Related Conditions & MeSH terms

• Angina, Unstable
• Diabetes Mellitus
• Neointima

Intervention

Drug:
• Nicorandil
Nicorandil is given once before PCI and given 3 times daily for 30 days after PCI.
• nicorandil placebo
Nicorandil placebo is given once before PCI and given 3 times daily for 30 days after PCI.

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Zhang Ying Qian

Country where clinical trial is conducted

China, 

References & Publications (8)

Chen J, Zhou S, Jin J, Tian F, Han Y, Wang J, Liu J, Chen Y. Chronic treatment with trimetazidine after discharge reduces the incidence of restenosis in patients who received coronary stent implantation: a 1-year prospective follow-up study. Int J Cardiol. 2014 Jul 1;174(3):634-9. doi: 10.1016/j.ijcard.2014.04.168. Epub 2014 Apr 21. — View Citation

Horinaka S, Yabe A, Yagi H, Ishimitsu T, Yamazaki T, Suzuki S, Kohro T, Nagai R; JCAD Study Investigators. Effects of nicorandil on cardiovascular events in patients with coronary artery disease in the Japanese Coronary Artery Disease (JCAD) study. Circ J. 2010 Mar;74(3):503-9. Epub 2010 Jan 18. — View Citation

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. Erratum in: Lancet 2002 Sep 7;360(9335):806. — View Citation

Kawai Y, Hisamatsu K, Matsubara H, Dan K, Akagi S, Miyaji K, Munemasa M, Fujimoto Y, Kusano KF, Ohe T. Intravenous administration of nicorandil immediately before percutaneous coronary intervention can prevent slow coronary flow phenomenon. Eur Heart J. 2009 Apr;30(7):765-72. doi: 10.1093/eurheartj/ehp077. Epub 2009 Mar 10. — View Citation

Machecourt J, Danchin N, Lablanche JM, Fauvel JM, Bonnet JL, Marliere S, Foote A, Quesada JL, Eltchaninoff H, Vanzetto G; EVASTENT Investigators. Risk factors for stent thrombosis after implantation of sirolimus-eluting stents in diabetic and nondiabetic patients: the EVASTENT Matched-Cohort Registry. J Am Coll Cardiol. 2007 Aug 7;50(6):501-8. Epub 2007 Jul 23. — View Citation

Nagoshi R, Shinke T, Otake H, Shite J, Matsumoto D, Kawamori H, Nakagawa M, Kozuki A, Hariki H, Inoue T, Ohsue T, Taniguchi Y, Iwasaki M, Nishio R, Hiranuma N, Konishi A, Kinutani H, Miyoshi N, Takaya T, Yamada S, Yasaka Y, Hayashi T, Yokoyama M, Kato H, Kadotani M, Ohnishi Y, Hirata K. Qualitative and quantitative assessment of stent restenosis by optical coherence tomography: comparison between drug-eluting and bare-metal stents. Circ J. 2013;77(3):652-60. Epub 2012 Dec 21. — View Citation

Shehata M. Cardioprotective effects of oral nicorandil use in diabetic patients undergoing elective percutaneous coronary intervention. J Interv Cardiol. 2014 Oct;27(5):472-81. doi: 10.1111/joic.12142. Epub 2014 Aug 30. — View Citation

Tian F, Chen Y, Liu H, Zhang T, Guo J, Jin Q. Assessment of characteristics of neointimal hyperplasia after drug-eluting stent implantation in patients with diabetes mellitus: an optical coherence tomography analysis. Cardiology. 2014;128(1):34-40. doi: 10.1159/000357612. Epub 2014 Feb 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neointimal thickness (in µm)	Neointimal thickness is defined as the distance between the stent strut and lumen surface.	9 month	No
Primary	Neointimal area	Stent and lumen areas will be measured, and neointimal area is calculated as stent area minus lumen area.	9 month	No
Secondary	number of uncovered stent struts		9 month	No
Secondary	percent of uncovered stent struts		9 month	No
Secondary	characteristics of neointima (number of homogenous neointimal,number of layered neointima, number of heterogeneous neointima)	The characteristics of neointimal hyperplasia will be assessed and classified into three patterns according to the neointimal signal intensity.	9 month	No
Secondary	number of in-stent neoatherosclerosis		9 month	No
Secondary	angiographic late lumen loss (in mm)	Late lumen loss is the difference of baseline and follow-up minimal luminal diameters.	9 month	No
Secondary	rate of restenosis (in %)		9 month	No
Secondary	number of major adverse cardiovascular events		9 month	No