HypertensionPhase 4NCT00139386
Candesartan for Prevention of Cardiovascular Events After Cypher or Taxus Coronary Stenting (4C) Trial
A Phase 4 study testing Candesartan in people with Hypertension and Coronary Artery Disease, run by Kumamoto University at 1 site in Japan.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hypertension, Coronary Artery Disease
- What is being tested?
- Candesartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,119 participants
- Where
- 1 siteJapan
- Study dates
- Oct 2005to Apr 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Severe renal or hepatic disease
- Candidates for coronary artery bypass grafting (CABG)
- Within 3 months after CABG
- Allergic history to candesartan
- Pregnant women
Trial locations and contacts
1 site in 1 country.
Japan1 site
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
Kumamoto, 860-8556
About this study
Official title: Effects of Candesartan Cilexetil on Cardiovascular Events in Japanese Patients With Hypertension After Sirolimus- or Paclitaxel-Eluting Stents Implantation
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.
Read the 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%.
- Conditions
- Hypertension, Coronary Artery Disease
- Being tested
- Candesartan
- Keywords
- Drug-eluting stent, Candesartan, Randomized control study, Coronary Angioplasty
- Medical subject headings
- Hypertension, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CandesartanDrug
Also called Blopress, 4C
Candesartan Cilexetil (4-12 mg per day)
| Study group | Role | What they receive |
|---|---|---|
| Candesratan | Active comparator | Not described Receives: Drug: Candesartan |
| Non-candesartan | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 3 years
Secondary outcomes (7)
Target lesion revascularization
Measured: 3 years
Binary restenosis
Measured: 3 years
Newly onset diabetes
Measured: 3 years
Newly onset atrial fibrillation
Measured: 3 yeard
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
Measured: 3 years
Major adverse cardiac-related events
A composite of cardiovascular death, non-fatal myocardial infarction, unstable angina required admission and heart failure required admission
Measured: 3 years
Major cardiac-related events
A composite of non-fatal myocardial infarction, unstable angina required admission and heart failure required admission
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2005 (estimated)
- Study startOct 2005
- Primary completionApr 2009
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,119 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kumamoto University
- Sponsor type
- University, hospital or other
- Collaborators
- The 4C trial bureau, Japan Heart Foundation
- Responsible party
- Principal investigator, Hisao Ogawa, Kumamoto University
- Investigators
- Hisao Ogawa, MD, PhD, Study chair, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00139386
- Sponsor's protocol ID
- CVM-RCT-2005-01
- Status last verified
- Apr 2013
- First submitted
- 29 Aug 2005
- Last updated
- 18 Apr 2013
- Results posted
- No
- Data monitoring committee
- Yes
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. doi: 10.1016/S0002-8703(03)00443-5.
PubMed 14661009Sakamoto T, Ogawa H, Nakao K, Hokimoto S, Tsujita K, Koide S, Yamamoto N, Shimomura H, Matsumura T, Oshima S, Kikuta K, Oka H, Kimura K, Matsui K; 4C (Candesartan for Prevention of Cardiovascular Events after CYPHER or TAXUS Coronary Stenting) study investigators. Impact of candesartan on cardiovascular events after drug-eluting stent implantation in patients with coronary artery disease: The 4C trial. J Cardiol. 2016 Apr;67(4):371-7. doi: 10.1016/j.jjcc.2015.06.009. Epub 2015 Aug 4.
PubMed 26254019
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Candesartan Cilexetil on Cardiovascular Events in Japanese Patients With Hypertension After Sirolimus- or Paclitaxel-Eluting Stents Implantation
- ClinicalTrials.gov ID
- NCT00139386
- Acronym / sponsor ID
- CVM-RCT-2005-01
- Conditions
- Hypertension, Coronary Artery Disease
- Keywords
- Drug-eluting stent, Candesartan, Randomized control study, Coronary Angioplasty
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,119 participants (actual)
- Lead sponsor
- Kumamoto UniversityUniversity, hospital or other
- Collaborators
- The 4C trial bureau, Japan Heart Foundation
- Study start
- Oct 2005
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 31 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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%.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Candesratan | Active comparator | Drug: Candesartan |
| Non-candesartan | No intervention | – |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- Severe renal or hepatic disease
- Candidates for coronary artery bypass grafting (CABG)
- Within 3 months after CABG
- Allergic history to candesartan
- Pregnant women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CandesartanAlso: Blopress, 4CCandesartan Cilexetil (4-12 mg per day) | Drug | Candesratan |
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)
Time frame: 3 years
7 secondary outcomes
Target lesion revascularization
Time frame: 3 years
Binary restenosis
Time frame: 3 years
Newly onset diabetes
Time frame: 3 years
Newly onset atrial fibrillation
Time frame: 3 yeard
Each of the primary endpoint events
Time frame: 3 years
Major adverse cardiac-related events
Time frame: 3 years
Major cardiac-related events
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2013.
- Background: PubMed 14661009Kondo 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. doi: 10.1016/S0002-8703(03)00443-5.
- Derived from this study: PubMed 26254019Sakamoto T, Ogawa H, Nakao K, Hokimoto S, Tsujita K, Koide S, Yamamoto N, Shimomura H, Matsumura T, Oshima S, Kikuta K, Oka H, Kimura K, Matsui K; 4C (Candesartan for Prevention of Cardiovascular Events after CYPHER or TAXUS Coronary Stenting) study investigators. Impact of candesartan on cardiovascular events after drug-eluting stent implantation in patients with coronary artery disease: The 4C trial. J Cardiol. 2016 Apr;67(4):371-7. doi: 10.1016/j.jjcc.2015.06.009. Epub 2015 Aug 4.
- Dept of CVM, Kumamoto Univ HospLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hisao Ogawa, MD, PhD study chair
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Candesartan in people with Hypertension and Coronary Artery Disease, run by Kumamoto University at 1 site in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00139386, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2013.