Efficacy Study of Nicorandil on Neointima

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

Detailed Description
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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.

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

Conditions
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Angina, Unstable, Diabetes Mellitus

Intervention / Treatment
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* Drug: Nicorandil
* Drug: nicorandil placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicorandil group<br>Drug: Nicorandil (Chugai Pharmaceutical Co, Japan). The first dose is given 8h before selective percutaneous coronary intervention, 10mg, oral. After the percutaneous coronary intervention, nicorandil is given for 30 days, 5mg each time, 3 times daily oral. | Drug: Nicorandil<br>* Nicorandil is given once before PCI and given 3 times daily for 30 days after PCI.<br>* Other names: Sigmart;|
| Placebo Comparator: Control group<br>Drug: Nicorandil placebo (Sihuan Pharmaceutical Co, China). The first dose is given 8h before selective percutaneous coronary intervention, 2 tablets, oral. After the percutaneous coronary intervention, placebo is given for 30 days, 1 tablet each time, 3 times daily oral. | Drug: nicorandil placebo<br>* Nicorandil placebo is given once before PCI and given 3 times daily for 30 days after PCI.<br>* Other names: no other names;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neointimal thickness (in μm) | Neointimal thickness is defined as the distance between the stent strut and lumen surface. | 9 month | 
| Neointimal area | Stent and lumen areas will be measured, and neointimal area is calculated as stent area minus lumen area. | 9 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of uncovered stent struts |  | 9 month | 
| percent of uncovered stent struts |  | 9 month | 
| 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 | 
| number of in-stent neoatherosclerosis |  | 9 month | 
| angiographic late lumen loss (in mm) | Late lumen loss is the difference of baseline and follow-up minimal luminal diameters. | 9 month | 
| rate of restenosis (in %) |  | 9 month | 
| number of major adverse cardiovascular events |  | 9 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neointima, Tomography, Optical Coherence, drug-eluting stents, Nicorandil