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

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00095238
First received: November 1, 2004
Last updated: May 5, 2010
Last verified: May 2010
  Purpose

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.


Condition Intervention Phase
Congestive Heart Failure
Drug: Irbesartan
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Irbesartan in Heart Failure With Preserved Systolic Function (I-Preserve)

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Percentage of Participants With First Occurrence of the Composite Outcome of Death (All Cause) or Protocol-Specified Cardiovascular (CV) Hospitalization at Given Timepoints [ Time Frame: Year 1, Year 2, Year 3, Year 4, Year 5 ] [ Designated as safety issue: No ]
    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:
  • Percentage of Participants Experiencing Heart Failure Mortality or Heart Failure Hospitalization at Given Time Points [ Time Frame: Year 1, Year 2, Year 3, Year 4, Year 5 ] [ Designated as safety issue: No ]
    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 Month 6 and Month 14 [ Time Frame: Baseline, Month 6, Month 14 ] [ Designated as safety issue: No ]
    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.

  • Minnesota Living With Heart Failure (MLwHF) Total Score (Sum of Questions 1-21) at Final Visit [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in B-Type Natriuretic Peptide (Pro-BNP) at Month 6 and Month 14 [ Time Frame: Baseline, Month 6, Month 14 ] [ Designated as safety issue: Yes ]
    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 CV Death, Non-Fatal Myocardial Infarction (MI), or Non-Fatal Stroke at Given Timepoints [ Time Frame: Year 1, Year 2, Year 3, Year 4, Year 5 ] [ Designated as safety issue: No ]
    Treatment comparisons for time to cardiovascular death, non-fatal MI, or non-fatal stroke.

  • Percentage of Participants Experiencing Cardiovascular Death at Given Timepoints [ Time Frame: Year 1, Year 2, Year 3, Year 4, Year 5 ] [ Designated as safety issue: No ]
    Treatment comparisons for time to cardiovascular death

  • Percentage of Participants Experiencing All-cause Death at Given Time Points [ Time Frame: Year 1, Year 2, Year 3, Year 4, Year 5 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.

  • Participant Assessment of Heart Failure Status at Month 6, Month 14, and Final Visit Compared With Baseline [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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 Fatigue at Month 6, Month 14, and Final Visit Compared With Baseline [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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 [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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 CV Death or CV Hospitalization at Given Timepoints [ Time Frame: Year 1, Year 2, Year 3, Year 4, Year 5 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Experiencing Protocol-specified Cardiovascular (CV) Hospitalization at Given Timepoints [ Time Frame: Year 1, Year 2, Year 3, Year 4, Year 5 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With New Onset of Diabetes Among Subjects With No Prior Diabetes History at Given Timepoints [ Time Frame: Year 1, Year 2, Year 3, Year 4, Year 5 ] [ Designated as safety issue: Yes ]
    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 6, Month 18, and Month 30 [ Time Frame: Baseline, Month 6, Month 18, Month 30 ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in Glomerular Filtration Rate (GFR)at Month 42, Month 54, Month 66 [ Time Frame: Baseline, Month 42, Month 54, Month 66 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With New Onset Atrial Fibrillation (AF) Among Those With No Prior AF History or Evidence of AF on Baseline Electrocardiograph (ECG) [ Time Frame: Baseline, Final Visit ] [ Designated as safety issue: No ]
    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.


Enrollment: 4128
Study Start Date: June 2002
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: Irbesartan
Tablets, Oral, titration from 75 to 300 mg, once daily up to 6 years
Placebo Comparator: 2 Drug: Placebo
Tablets, Oral, titration from 75 to 300 mg, once daily up to 6 years

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00095238

  Show 231 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Sanofi
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00095238     History of Changes
Other Study ID Numbers: CV131-148
Study First Received: November 1, 2004
Results First Received: December 16, 2009
Last Updated: May 5, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases
Irbesartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014