Clinical trial NCT01475123: Prospective Study of End Stage Renal Disease Patients With Coronary Artery Disease Treated by Oral Nicorandil
Official title: Effects of Nicorandil on Cardiovascular Events in Patients With Coronary Artery Disease Receiving Hemodialysis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Coronary Artery Disease
End Stage Renal Disease
Keywords: Nicorandil
Randomized control study
Hemodialysis
Coronary Artery Disease
Lead sponsor: Kumamoto University
Sponsor class: OTHER
First posted: 2011-11-21
Enrollment: 268
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 2 years
Secondary outcomes:
measure: Total mortality
timeFrame: 2 years
measure: revascularization therapy
timeFrame: 2 years
measure: hospitalization for heart failure
timeFrame: 2 years
measure: hospitalization for peripheral artery disease
timeFrame: 2 years
measure: newly onset of atrial fibrillation
timeFrame: 2 years
Other outcomes:
Locations:
city: Kumamoto
country: Japan
facility: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
Study officials:
affiliation: Kumamoto University
name: Hisao Ogawa, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.