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 (OLMEBNP)

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

Study Overview

• Status: Terminated
• Conditions: Chronic Heart Failure; High Blood B-type (or Brain) Natriuretic Peptide (BNP) Level
• Intervention / Treatment: Drug: olmesartan medoxomil + candesartan cilexetil placebo; Drug: olmesartan medoxomil placebo + candesartan cilexetil

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bron, France
  • Cedex, France
  • Cholet, France
  • Langres, France
  • Mannheim, France
  • Pontoise, France
  • Roubaix, France
• Germany
  • Bad Nauheim, Germany
  • Berlin, Germany
  • Lambrecht, Germany
• Netherlands
  • Ad Delft, Netherlands

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 If a female becomes pregnant during the study, she has to be withdrawn immediately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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1	Drug: olmesartan medoxomil + candesartan cilexetil placebo; Dosage form: tablet; frequency: daily; duration: 24 weeks
EXPERIMENTAL: 2	Drug: olmesartan medoxomil placebo + candesartan cilexetil; Dosage form: tablets; frequency: daily; duration: 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute BNP change from week 0 to 24 of treatment	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of BNP responders at week 4, 8, 16 and 24 (BNP levels reduced to 350 pg/ml or less at all time points)	24 weeks maximum
BNP change from week 0 to week 4, 8, and 16	16 weeks maximum
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)	24 weeks
Event-free survival	24 weeks
Time-to-death	24 weeks
Time-to-first cardiovascular event	24 weeks maximum
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	24 weeks

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (ACTUAL): November 1, 2009
• Study Completion (ACTUAL): November 1, 2009

Study Registration Dates

• First Submitted: May 14, 2008
• First Submitted That Met QC Criteria: May 14, 2008
• First Posted (ESTIMATE): May 16, 2008

Study Record Updates

• Last Update Posted (ACTUAL): December 24, 2018
• Last Update Submitted That Met QC Criteria: December 20, 2018
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Olmesartan; Olmesartan Medoxomil; Candesartan; Candesartan cilexetil
• Other Study ID Numbers: DSE-866-45; 2007-003060-22 EUDRACT Number

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR