Study to Demonstrate the Non-inferiority of Olmesartan Medoxomil Versus Candesartan Cilexetil in Reducing Blood B-type (or Brain) Natriuretic Peptide Levels at Week 24

Official Title: “A 24-Week Multicentre, Randomized, Double-Blind, Controlled, Parallel Group Non-Inferiority Study to Assess the Efficacy and Safety of Olmesartan Medoxomil Versus Candesartan Cilexetil in Patients With Symptomatic Heart Failure (NYHA II-IV)”

This study will compare olmesartan medoxomil to candesartan cilexetil in reducing BNP, a prognostic biomarker of heart failure, at week 24

Intervention(s) in this Clinical Trial

• Drug: olmesartan medoxomil + candesartan cilexetil placebo
  • Dosage form: tablet; frequency: daily; duration: 24 weeks
• Drug: olmesartan medoxomil placebo + candesartan cilexetil
  • Dosage form: tablets; frequency: daily; duration: 24 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Experimental: 2

Primary Measures

• Absolute BNP change from week 0 to 24 of treatment
  • Time Frame: 24 weeks
    Safety Issue?: No

Secondary Measures

• Proportion of BNP responders at week 4, 8, 16 and 24 (BNP levels reduced to 350 pg/ml or less at all time points)
  • Time Frame: 24 weeks maximum
    Safety Issue?: No
• BNP change from week 0 to week 4, 8, and 16
  • Time Frame: 16 weeks maximum
    Safety Issue?: No
• Incidence of critical events at 24 weeks: All cause death; Cardiovascular death defined as death due to: HF, myocardial infarction, cardiac arrhythmia, stroke/cerebral vascular accident, other cardiovascular cause (e.g., aneurysm or pulmonary embolism)
  • Time Frame: 24 weeks
    Safety Issue?: No
• Event-free survival
  • Time Frame: 24 weeks
    Safety Issue?: No
• Time-to-death
  • Time Frame: 24 weeks
    Safety Issue?: No
• Time-to-first cardiovascular event
  • Time Frame: 24 weeks maximum
    Safety Issue?: No
• Change in clinical status: Improvement: patient alive without any cardiovascular event with an improvement of at least one NYHA functional class level; No change: patient alive without any cardiovascular event with stable functional NYHA class
  • Time Frame: 24 weeks
    Safety Issue?: No

Inclusion Criteria:

• Male or female, adult, out-patients aged between 18 and 85 years
• Patients with documented hospital admission within the previous 3 months before randomization with discharge diagnosis of CHF
• Patients with functional NYHA class II-IV with LVEF < 40% assessed within the last 3 months
• Patients with blood BNP levels > 400 pg/ml or NT-ProBNP levels > 1500 pg/ml
• Patients with CHF due to ischemic heart disease, idiopathic dilated cardiomyopathy (IDC), mitral or aortic insufficiency or hypertension
• Patients with stable conventional treatment with diuretics, ACEI and/or beta-blockers and/or aldosterone antagonists for at least 2 months prior to randomisation, unless documented contraindication or intolerance

Exclusion Criteria:

• Females who are pregnant or plan a pregnancy during the time of the trial, are nursing or are of childbearing potential and not using acceptable methods of contraception. If a female becomes pregnant during the study, she has to be withdrawn immediately
• Patients with current hospitalisation due to heart failure
• Patients with stroke or transient ischemic attack (TIA) within the last 3 months
• Patients with acute coronary syndrome, myocardial infarction, coronary artery bypass or angioplasty within 3 months
• Planned cardiac surgery, revascularization or resynchronization within the study period
• Patients with operable valvular disease or significant obstructive cardiomyopathy
• Patients with bradycardia [heart rate (HR) < 50 bpm]
• Patients with hypotension [systolic blood pressure (SBP) < 90 mmHg]
• Patients with obstructive pneumopathy
• Patients with clinical significant renal failure (creatininemia > 200 micromol/l)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 85 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Daiichi Sankyo Europe, GmbH Industry

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00679484

Study ID Number: DSE-866-45

ClinicalTrials.gov Identifier: NCT00679484

Health Authority: Germany: Federal Institute for Drugs and Medical Devices