Irbesartan in Heart Failure With Preserved Systolic Function (I-Preserve)

Phase 3

Completed

Conditions: Congestive Heart Failure

Interventions: Drug: Placebo
Drug: Irbesartan

Registration Number: NCT00095238

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: The purpose of this clinical research study is to learn if Irbesartan is superior to placebo in reducing mortality and cardiovascular morbidity in subjects with heart failure with preserved systolic function. The safety of this treatment will also be studied.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 4128

Inclusion Criteria

Male or female age >= 60 years with current symptoms of heart failure consistent with New York Heart Association (NYHA) class II-IV
Left ventricular ejection fraction (LVEF) > = 45%
Willing to provide written informed consent AND hospitalization for heart failure within the past 6 months OR various abnormalities in electrocardiogram, echocardiogram or chest x-ray indicating heart disease.

Exclusion Criteria

Acute myocardial infarction within 3 months;
Heart revascularization procedure within 3 months;
Hospitalization for angina within 3 months;
Other heart surgery
Life-threatening or uncontrolled arrhythmia
Subjects with an implantable cardioverter-defibrillator that has discharged in the past 3 months;
Stroke or surgery of the arteries in the brain within 3 months;
Serious lung disease which requires use of home oxygen.
Significantly low blood pressure
Significantly high blood pressure
Other known diseases that may limit life expectancy to <3 years;
Known or suspected bilateral kidney artery narrowing;
Geographic or social factors making study participation and follow-up impractical.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Placebo	-
1	Irbesartan	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With First Occurrence of the Composite Outcome of Death (All Cause) or Protocol-Specified Cardiovascular (CV) Hospitalization at Given Timepoints	Year 1, Year 2, Year 3, Year 4, Year 5	Treatment comparisons for time to first occurrence of composite outcome of all-cause death (composite outcome of death) or protocol-specified CV hospitalization. Protocol-specified CV hospitalizations include those ≥24 hrs or involving a calendar date change for a primary cause of worsening heart failure, unstable angina, myocardial infarction, ventricular or atrial dysrhythmia, or stroke, that also require intravenous or intramuscular therapy or a related procedure or significant augmentation of oral therapy. In addition, MI or stroke during any hospitalization are included.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Heart Failure Mortality or Heart Failure Hospitalization at Given Time Points	Year 1, Year 2, Year 3, Year 4, Year 5	Treatment comparisons for time to heart failure mortality or heart failure hospitalization
Minnesota Living With Heart Failure (MLwHF) Total Score (Sum of Questions 1-21) at Final Visit	Baseline, Final Visit=last scheduled visit specified in the protocol at conclusion of the entire study by the sponsor. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.	Mean score at baseline and final visit in Minnesota Living with Heart Failure (MLWHF) questionnaire, a 21-item, patient-reported, 6-point (ranging from 0-5; higher score=poorer quality of life; highest possible score=105) measurement of quality of life in persons with heart failure.
Participant Assessment of Fatigue at Month 6, Month 14, and Final Visit Compared With Baseline	Baseline, Month 6, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.	Assessments are directly based on the Case Report Form (CRF). If the post-randomization CRF assessment was missing and the subject died, was hospitalized for worsening heart failure, or discontinued study medication for worsening heart failure, the subject was considered as having a Major Event. Participants who are summarized under Major Events are categorized as Worsened Markedly.
Percentage of Participants With New Onset of Diabetes Among Subjects With No Prior Diabetes History at Given Timepoints	Year 1, Year 2, Year 3, Year 4, Year 5	Treatment comparisons for time to new onset of diabetes (from adverse event reporting) among subjects with no prior history of diabetes.
Mean Change From Baseline in Glomerular Filtration Rate (GFR)at Month 42, Month 54, Month 66	Baseline, Month 42, Month 54, Month 66	Based on the Cockcroft-Gault formula calculation, a commonly used surrogate marker to estimate creatinine clearance, which in turn is an approximate measure of GFR. It employs serum creatinine measurements and a patient's weight to predict the creatinine clearance. Adjusted for baseline GFR and angiotensin-converting enzyme inhibitor use at baseline (ACE-I). A decrease from baseline signifies worsening. The adjusted mean change from baseline value is from the model (calculated prior to rounding), whereas the other two points are the baseline mean and post mean.
Percentage of Participants Experiencing CV Death or CV Hospitalization at Given Timepoints	Year 1, Year 2, Year 3, Year 4, Year 5	Treatment comparisons for time to CV death or CV hospitalization. Protocol-specified CV hospitalizations include hospitalizations ≥24 hrs or involve a calendar date change for a primary cause of worsening heart failure, unstable angina, myocardial infarction, ventricular dysrhythmia, atrial dysrhythmia or stroke that also requires intravenous or intramuscular therapy or a related procedure or significant augmentation of oral therapy. Protocol specified CV hospitalizations also include myocardial infarction or stroke occurring during any hospitalization.
Minnesota Living With Heart Failure (MLwHF) Total Score (Sum of Questions 1-21) at Month 6 and Month 14	Baseline, Month 6, Month 14	Mean score and adjusted mean change from baseline in Minnesota Living with Heart Failure (MLWHF) questionnaire, a 21-item, patient-reported, 6-point (ranging from 0-5; higher score=poorer quality of life; highest possible score=105) measurement of quality of life in persons with heart failure.
Change From Baseline in B-Type Natriuretic Peptide (Pro-BNP) at Month 6 and Month 14	Baseline, Month 6, Month 14	Adjusted ratio to baseline in geometric mean in Pro-BNP in the blood. Ratio to Baseline = On-therapy geometric mean divided by baseline geometric mean. A lower score signifies improvement. Change from baseline adjusted for baseline value and angiotensin converting enzyme inhibitor use at baseline. Analysis uses natural logarithms of excretion rate values.
Percentage of Participants Experiencing Protocol-specified Cardiovascular (CV) Hospitalization at Given Timepoints	Year 1, Year 2, Year 3, Year 4, Year 5	Treatment comparisons for time to protocol-specified CV hospitalization. Protocol-specified CV hospitalizations include hospitalizations ≥24 hrs or involve a calendar date change for a primary cause of worsening heart failure, unstable angina, myocardial infarction, ventricular dysrhythmia, atrial dysrhythmia or stroke that also requires intravenous or intramuscular therapy or a related procedure or significant augmentation of oral therapy. Protocol specified CV hospitalizations also include myocardial infarction or stroke occurring during any hospitalization.
Number of Participants With New Onset Atrial Fibrillation (AF) Among Those With No Prior AF History or Evidence of AF on Baseline Electrocardiograph (ECG)	Baseline, Final Visit	Frequency of new onset AF in participants with no prior AF history or evidence of AF on baseline ECG. Stratified by use of angiotensin-converting enzyme (ACE) inhibitors and measured by adverse events reporting and final ECG recording read by the investigator.
Percentage of Participants Experiencing CV Death, Non-Fatal Myocardial Infarction (MI), or Non-Fatal Stroke at Given Timepoints	Year 1, Year 2, Year 3, Year 4, Year 5	Treatment comparisons for time to cardiovascular death, non-fatal MI, or non-fatal stroke.
Participant Assessment of Heart Failure Status at Month 6, Month 14, and Final Visit Compared With Baseline	Baseline, Month 6, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.	Assessments are directly based on the Case Report Form (CRF). If the post-randomization CRF assessment was missing and the subject died, was hospitalized for worsening heart failure, or discontinued study medication for worsening heart failure, the subject was considered as having a Major Event. Participants who are summarized under Major Events are categorized as Worsened Markedly.
Participant Assessment of Dyspnea at Month 6, Month 14, and Final Visit Compared With Baseline	Baseline, Month 6, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.	Assessments are directly based on the Case Report Form (CRF). If the post-randomization CRF assessment was missing and the subject died, was hospitalized for worsening heart failure, or discontinued study medication for worsening heart failure, the subject was considered as having a Major Event. Participants who are summarized under Major Events are categorized as Worsened Markedly.
Percentage of Participants Experiencing Cardiovascular Death at Given Timepoints	Year 1, Year 2, Year 3, Year 4, Year 5	Treatment comparisons for time to cardiovascular death
Percentage of Participants Experiencing All-cause Death at Given Time Points	Year 1, Year 2, Year 3, Year 4, Year 5	Treatment comparisons for time to all-cause death
Change From Baseline in the New York Heart Association (NYHA) Functional Class at Month 6, Month 10, Month 14, and Final Visit	Baseline, Month 6, Month 10, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.	NYHA functional classification=4-tiered system relating symptoms to everyday activities \& quality of life. (See Reporting Groups for description of each class.) Change of NYHA functional class from baseline was grouped into 3 categories: improved, unchanged, or worsened (based on case report form \[CRF\] assessment). If a post-randomization CRF assessment was missing or participant died, was hospitalized for worsening heart failure or discontinued study medication for worsening heart failure, the participant was classified as Major Event.
Physician Assessment of Heart Failure Status at Month 6, Month 14, and Final Visit Compared With Baseline	Baseline, Month 6, Month 14, Final Visit. The trial was designed to end after 1440 primary endpoint events, projected duration=6.0 ± 0.5 years.	This was an assessment of the change in overall physician opinion of change from baseline status. Assessments are directly based on the Case Report Form (CRF). If the post-randomization CRF assessment was missing and the subject died, was hospitalized for worsening heart failure, or discontinued study medication for worsening heart failure, the subject was considered as having a Major Event. Participants who are summarized under Major Events are categorized as Worsened Markedly.
Mean Change From Baseline in Glomerular Filtration Rate (GFR) at Month 6, Month 18, and Month 30	Baseline, Month 6, Month 18, Month 30	Based on the Cockcroft-Gault formula calculation, a commonly used surrogate marker to estimate creatinine clearance, which in turn is an approximate measure of GFR. It employs serum creatinine measurements and a patient's weight to predict the creatinine clearance. Adjusted for baseline GFR and angiotensin-converting enzyme inhibitor use at baseline (ACE-I). A decrease from baseline signifies worsening. The adjusted mean change from baseline value is from the model (calculated prior to rounding), whereas the other two points are the baseline mean and post mean.