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

This study has been completed.
Sponsor:
Collaborators:
The 4C trial bureau
Japan Heart Foundation
Information provided by (Responsible Party):
Hisao Ogawa, Kumamoto University
ClinicalTrials.gov Identifier:
NCT00139386
First received: August 29, 2005
Last updated: April 17, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Hypertension
Coronary Artery Disease
Drug: Candesartan
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Effects of Candesartan Cilexetil on Cardiovascular Events in Japanese Patients With Hypertension After Sirolimus- or Paclitaxel-Eluting Stents Implantation

Resource links provided by NLM:


Further study details as provided by Kumamoto University:

Primary Outcome Measures:
  • 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) [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Target lesion revascularization [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Binary restenosis [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Newly onset diabetes [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Newly onset atrial fibrillation [ Time Frame: 3 yeard ] [ Designated as safety issue: No ]
  • Each of the primary endpoint events [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    All cause of death, cardiovascular death, non-fatal myocardial infarction, unstable angina required admission, heart failure required admission and stroke

  • Major adverse cardiac-related events [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    A composite of cardiovascular death, non-fatal myocardial infarction, unstable angina required admission and heart failure required admission

  • Major cardiac-related events [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    A composite of non-fatal myocardial infarction, unstable angina required admission and heart failure required admission


Enrollment: 1119
Study Start Date: October 2005
Study Completion Date: April 2012
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Candesratan Drug: Candesartan
Candesartan Cilexetil (4-12 mg per day)
Other Names:
  • Blopress
  • 4C
No Intervention: Non-candesartan

Detailed 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%.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00139386

Locations
Japan
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
Kumamoto, Japan, 860-8556
Sponsors and Collaborators
Kumamoto University
The 4C trial bureau
Japan Heart Foundation
Investigators
Study Chair: Hisao Ogawa, MD, PhD Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
  More Information

Additional Information:
Publications:
Responsible Party: Hisao Ogawa, MD, PhD, Kumamoto University
ClinicalTrials.gov Identifier: NCT00139386     History of Changes
Other Study ID Numbers: CVM-RCT-2005-01
Study First Received: August 29, 2005
Last Updated: April 17, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Kumamoto University:
Drug-eluting stent
Candesartan
Randomized control study
Coronary Angioplasty

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Hypertension
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Candesartan cilexetil
Candesartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014