Prospective Study of End Stage Renal Disease Patients With Coronary Artery Disease Treated by Oral Nicorandil

Effects of Nicorandil on Cardiovascular Events in Patients With Coronary Artery Disease Receiving Hemodialysis

Nicorandil is potentially effective to prevent cardiovascular events in patients with coronary artery disease (CAD) receiving hemodialysis. The purpose of this study is to prospectively investigate whether nicorandil is effective in reducing the incidence of cardiovascular events in patients with CAD on hemodialysis.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Artery Disease; End Stage Renal Disease
• Intervention / Treatment: Drug: Nicorandil

Detailed Description

Patients on hemodialysis for end-stage renal disease are at high risk for death from ischemic heart disease. It was reported that nicorandil, a hybrid compound on adenosine triphosphate-sensitive potassium channel opener and nitric oxide door, was potentially effective to prevent cardiovascular events in patients with CAD receiving hemodialysis. Therefore, investigators prospectively examine whether nicorandil is effective in reducing the incidence of cardiovascular events in patients with CAD on hemodialysis.

The primary endpoint is a composite of cardiovascular death, sudden cardiac death, nonfatal myocardial infarction, hospitalization for recurrent symptomatic myocardial ischemia and stroke. The secondary endpoints are total mortality, revascularization therapy, hospitalization for heart failure, hospitalization for peripheral artery disease and newly onset of atrial fibrillation.

Patient population that needs to prove the hypothesis is estimate to be 300 cases in total (150 cases in each group). Investigators set the parameters which are need to calculate the number of study patients as follows; drop out rate 10%, an event rate of the primary end point for two years 50%, a risk reduction rate brought by nicorandil 60%, a statistical power 80% and two-sided significant level 0.05. Investigators referred the event rate and the risk reduction rate from the previous study by Ishi H et al. In this study, event rate of the primary end point for two years was 50% and the risk reduction brought by nicorandil was 60%. Event rate of the present study will be lower, because drug-eluting stents are widely used to prevent restenosis in the present era. Moreover, investigators include the patients underwent coronary bypass graft in the present study. In addition, non-cardiovascular mortality is high in the patients on hemodialysis. Considering all the various factors together, investigators estimated the study sample size.

• Study Type: Interventional
• Enrollment (Actual): 268
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Kumamoto, Japan, 860-8556
    • Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Eligible patients are who meet the following criteria:

• Patient with previously diagnosed coronary artery disease (significant coronary artery stenosis is defined as > 75% narrowing of the artery lumen)
• Patients who continued hemodialysis for more than one month

Exclusion Criteria:

• Within one month after acute myocardial infarction
• Within 3 months after coronary artery bypass graft (CABG)
• Treatment with phosphodiesterase type 5 inhibitor
• Candidates for carotid artery stenting
• Severe disease requiring active medical treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nicorandil; Nicorandil was administered orally (15mg/day).	Drug: Nicorandil; 15mg per day; Other Names: Sigmart
No Intervention: Non-nicorandil; Nicorandil was not administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint is composite of :1) cardiovascular death 2)sudden cardiac death 3)nonfatal myocardial infarction 4)Hospitalization for recurrent symptomatic myocardial ischemia 5)stroke	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
hospitalization for heart failure	2 years
Total mortality	2 years
revascularization therapy	2 years
hospitalization for peripheral artery disease	2 years
newly onset of atrial fibrillation	2 years

Collaborators and Investigators

• Sponsor: Kumamoto University
• Investigators: Study Chair: Hisao Ogawa, MD, PhD, Kumamoto University

Publications and helpful links

General Publications

• Ishii H, Toriyama T, Aoyama T, Takahashi H, Yamada S, Kasuga H, Ichimiya S, Kanashiro M, Mitsuhashi H, Maruyama S, Matsuo S, Naruse K, Matsubara T, Murohara T. Efficacy of oral nicorandil in patients with end-stage renal disease: a retrospective chart review after coronary angioplasty in Japanese patients receiving hemodialysis. Clin Ther. 2007 Jan;29(1):110-22. doi: 10.1016/j.clinthera.2007.12.020.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): June 1, 2011
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: November 16, 2011
• First Submitted That Met QC Criteria: November 18, 2011
• First Posted (Estimated): November 21, 2011

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 11, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Randomized control study; Hemodialysis; Nicorandil
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Heart Diseases; Chronic Disease; Disease Attributes; Renal Insufficiency; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Renal Insufficiency, Chronic; Pathological Conditions, Signs and Symptoms; Coronary Artery Disease; Kidney Failure, Chronic; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Acids, Heterocyclic; Niacinamide; Nicotinic Acids; Nitrates; Nicorandil
• Other Study ID Numbers: CVM-2008-PRECON

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED