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

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

Official Title
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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)

Conditions
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Chronic Heart Failure, High Blood B-type (or Brain) Natriuretic Peptide (BNP) Level

Intervention / Treatment
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* Drug: olmesartan medoxomil + candesartan cilexetil placebo
* Drug: olmesartan medoxomil placebo + candesartan cilexetil


Participation Criteria
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Eligibility Criteria
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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 If a female becomes pregnant during the study, she has to be withdrawn immediately Patients with current hospitalisation due to heart failure Patients with stroke or transient ischemic attack (TIA) within the last 3 months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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: olmesartan medoxomil + candesartan cilexetil placebo<br>* Dosage form: tablet; frequency: daily; duration: 24 weeks<br>|
| Experimental: 2<br> | Drug: olmesartan medoxomil placebo + candesartan cilexetil<br>* Dosage form: tablets; frequency: daily; duration: 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |