Candesartan for Prevention of Cardiovascular Events After Cypher or Taxus Coronary Stenting (4C) Trial

Hypertension Clinical Trial

Official title:

Effects of Candesartan Cilexetil on Cardiovascular Events in Japanese Patients With Hypertension After Sirolimus- or Paclitaxel-Eluting Stents Implantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00139386
• Other study ID #: CVM-RCT-2005-01
• Status: Completed
• Phase: Phase 4
• First received: August 29, 2005
• Last updated: April 17, 2013
• Start date: October 2005
• Est. completion date: April 2012

Study information

• Verified date: April 2013
• Source: Kumamoto University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

Candesartan is effective in preventing cardiovascular events in patients without restenosis after coronary angioplasty. Therefore, the investigators hypothesized that candesartan after drug-eluting stent (DES) implantation was also effective in preventing cardiovascular events.

The purpose of this study is to investigate whether an angiotensin II receptor blocker, candesartan, is effective in reducing the incidence of cardiovascular events after drug-eluting stent implantation.

Description:

It was reported that low-dose angiotensin II receptor blocker, candesartan, was effective to prevent cardiovascular events in patients with coronary artery disease treated with coronary angioplasty (Am Heart J 146:E20, 2003). In this study, patients without significant coronary stenosis on follow-up angiography 6 months after intervention were randomly assigned into a candesartan group (baseline treatment plus candesartan 4 mg/d) or a control group (baseline treatment alone). It is well known that patients treated with drug-eluting stents (DES) have lower restenosis rate as compared with those with bare metal stents. Therefore, we hypothesized that candesartan started immediately after DES implantation was effective to prevent cardiovascular events.

The primary endpoint is a composite of any cause death and cardiovascular events (nonfatal myocardial infarction, recurrent symptomatic myocardial ischemia, congestive heart failure, and stroke). The secondary endpoints are target lesion revascularization, binary restenosis, newly onset diabetes and newly onset of atrial fibrillation.

Patient population which needs to prove the hypothesis is estimates to be 1,130 cases in total (565 cases in each group). We set the parameters which are needed to calculate the number of study patients as follows; a drop out rate 10%, an event rate of the primary end point for 3 years 20%, a risk reduction rate brought by candesartan 25%, a statistical power 90% and a two-sided significance level 0.05. We assumed the event rate from the study which was conducted to prove the effects of statins after PCI in Japan named MUSASHI-PCI. Also the risk reduction rate from two major RCTs of candesartan conducted in Japan named the Ogaki and HIJ-CREATE studies. In the Ogaki study, the risk reduction rate by candesartan was 52%. However, stents used in the study were only BMS after surviving restenosis. The risk reduction of the present study will be lower because of the higher onset rate of stent thrombosis in regard to DES. Furthermore, the risk reduction rate of candesartan for Japanese was 11% reported in HIJ-CREATE. The ACE-I usage rate was almost 70% in the control subjects of HIJ-CREATE. In the present study, ACE-I will be administered less frequently as low as 30%. Therefore, assumed risk reduction rate by candesartan in the present study could be higher. Considering all the various factors together, a reasonable risk reduction rate could be 25%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1119
• Est. completion date: April 2012
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• A. Patients with hypertension, systolic blood pressure (SBP) = or > 140 and/or diastolic blood pressure (DBP) = or > 90

• B. Patients with symptomatic heart failure lasting at least for 4 weeks (NYHA class = or > II), or those need continuous use of diuretics

• C. Patients underwent coronary angioplasty with drug-eluting stents

Eligible patients are those who meet (A or B) and C.

Exclusion Criteria:

• Severe renal or hepatic disease

• Candidates for coronary artery bypass grafting (CABG)

• Within 3 months after CABG

• Allergic history to candesartan

• Pregnant women

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Hypertension
• Myocardial Ischemia

Intervention

Drug:
• Candesartan
Candesartan Cilexetil (4-12 mg per day)

Locations

Country	Name	City	State
Japan	Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University	Kumamoto

Sponsors (3)

Lead Sponsor	Collaborator
Kumamoto University	Japan Heart Foundation, The 4C trial bureau

Country where clinical trial is conducted

Japan, 

References & Publications (1)

Kondo J, Sone T, Tsuboi H, Mukawa H, Morishima I, Uesugi M, Kono T, Kosaka T, Yoshida T, Numaguchi Y, Matsui H, Murohara T, Okumura K. Effects of low-dose angiotensin II receptor blocker candesartan on cardiovascular events in patients with coronary artery disease. Am Heart J. 2003 Dec;146(6):E20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint is a composite of: 1)any cause mortality and 2)cardiovascular events (non-fatal MI, drug-resistant AP required hospital admission, heart failure required hospital admission and stroke)		3 years	No
Secondary	Target lesion revascularization		3 years	No
Secondary	Binary restenosis		3 years	No
Secondary	Newly onset diabetes		3 years	No
Secondary	Newly onset atrial fibrillation		3 yeard	No
Secondary	Each of the primary endpoint events	All cause of death, cardiovascular death, non-fatal myocardial infarction, unstable angina required admission, heart failure required admission and stroke	3 years	No
Secondary	Major adverse cardiac-related events	A composite of cardiovascular death, non-fatal myocardial infarction, unstable angina required admission and heart failure required admission	3 years	No
Secondary	Major cardiac-related events	A composite of non-fatal myocardial infarction, unstable angina required admission and heart failure required admission	3 years	No

External Links

•   Dept of CVM, Kumamoto Univ Hosp