Candesartan for Prevention of Cardiovascular Events After Cypher or Taxus Coronary Stenting (4C) Trial
Information source: Kumamoto University
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypertension; Coronary Artery Disease
Intervention: Candesartan (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Kumamoto University Official(s) and/or principal investigator(s): Hisao Ogawa, MD, PhD, Study Chair, Affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
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.
Clinical Details
Official title: Effects of Candesartan Cilexetil on Cardiovascular Events in Japanese Patients With Hypertension After Sirolimus- or Paclitaxel-Eluting Stents Implantation
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: 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)
Secondary outcome: Target lesion revascularizationBinary restenosis Newly onset diabetes Newly onset atrial fibrillation Each of the primary endpoint events Major adverse cardiac-related events Major cardiac-related events
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
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Additional Information
Dept of CVM, Kumamoto Univ Hosp
Related publications: 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.
Starting date: October 2005
Last updated: April 17, 2013
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