Valsartan in Cardiovascular Disease With Renal Dysfunction (The V-CARD) Study

Effects of Valsartan on Cardiovascular Events in Patients With Renal Dysfunction

The purpose of this study is to investigate if an angiotensin II receptor blocker, valsartan 160 mg/day is more effective to reduce the incidence of cardiovascular events as compared to 40 mg/day in patients with moderate renal dysfunction.

Study Overview

• Status: Terminated
• Conditions: Hypertension
• Intervention / Treatment: Drug: valsartan

Detailed Description

It is well known that patients with renal dysfunction have a poor prognosis concerning cardiovascular diseases. That is called "cardiorenal syndrome". It was reported that valsartan was effective in reducing the urine albumin extraction rate in patients with hyper- or normotension. We hypothesized that valsartan was more effective to prevent cardiovascular events by the intermediary of improving renal function.

The primary endpoints are:

• cardiovascular events (cardiac death, non-fatal myocardial infarction, unstable angina requiring rehospitalization, congestive heart failure requiring rehospitalization, revascularization procedures including coronary angioplasty or coronary artery bypass grafting;Stroke or transient ischaemic attack, dissociation aneurysm of the aorta needing hospitalisation;Lower limbs artery obstruction needing hospitalisation .
• end-stage renal dysfunction (introduction of hemodialysis or kidney transplantation)
• 50% reduction of creatinine clearance

The secondary endpoints are:

• systolic and diastolic function of the left ventricle estimated by echocardiography (% FS and E/A ratio)
• specific biochemical markers for cardiac or renal function (urine microalbumin, plasma B-type natriuretic peptide, plasma type 1 plasminogen activator inhibitor, plasma cystatin C)
• % changes of creatinine clearance between start and end of the study period
• transition of 1/(serum Cr) in patients whose u-prot/u-Cr is equal to or more than 1.0
• transition of serum K
• HbA1c
• New onset Atrial Fibrillation
• New onset Diabetes

• Study Type: Interventional
• Enrollment (Actual): 1000
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Kumamoto, Japan, 860-8556
    • Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
  • Kumamoto, Japan, 860-8556
    • Department of Cardiovascular Medicine, Kumamoto University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria (all required):

• Systolic blood pressure (SBP) >/= 140 and/or diastolic blood pressure (DBP) >/= 90 (untreated hypertension cases); or SBP>/=130 and/or DBP>/=80 (treated hypertension cases)
• Patients with coronary artery disease (more than 50% stenosis on coronary angiography [CAG], coronary computed tomography [CT] or coronary magnetic resonance angiography [MRA]; coronary spasm; or history of percutaneous coronary intervention [PCI]);Unstable angina patient
• Creatinine clearance between 30.0 and 89.9 ml/min

Exclusion Criteria (at least one of following):

• Reduced left ventricular (LV) function (ejection fraction [EF] equal to or less than 40%)
• Hyperpotassemia (serum potassium equal to or more than 5.5 mEq/l)
• Rapid progressive glomerular nephritis
• Nephrotic syndrome
• Renal artery stenosis
• Uncontrolled diabetes (HbA1c equal to or more than 9.0%)
• History of allergy to valsartan
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Valsartan 40mg; Standard Dose valsartan	Drug: valsartan; valsartan 40 or 160 (80) mg per day
Active Comparator: Valsartan 160mg; High Dose valsartan	Drug: valsartan; valsartan 40 or 160 (80) mg per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cardiovascular events	2 years
End-stage renal dysfunction	2 years
50% reduction of creatinine clearance	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
HbA1c	2 years
% FS and E/A ratio	2 years
Specific biochemical markers for cardiac or renal function	6 months and 1 year and 2 years
% changes of creatinine clearance	2 years
1/(serum Cr)	2 years
Serum K	2 years
U-prot/U-Cr	2 years
Adverse drug effects	2 years
New onset Atrial Fibrillation	2 years

Collaborators and Investigators

• Sponsor: Kumamoto University
• Investigators: Study Chair: Hisao Ogawa, MD, PhD, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: August 31, 2005
• First Submitted That Met QC Criteria: August 31, 2005
• First Posted (Estimate): September 1, 2005

Study Record Updates

• Last Update Posted (Estimate): February 26, 2016
• Last Update Submitted That Met QC Criteria: February 25, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Cardiovascular events; Renal dysfunction; Valsartan; Cardiorenal syndrome
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan
• Other Study ID Numbers: CVM-RCT-2005-02