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

Congestive Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00095238
• Other study ID #: CV131-148
• Status: Completed
• Phase: Phase 3
• First received: November 1, 2004
• Last updated: March 18, 2015
• Start date: June 2002
• Est. completion date: July 2008

Study information

• Verified date: March 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4128
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure

Intervention

Drug:
• Irbesartan
Tablets, Oral, titration from 75 to 300 mg, once daily up to 6 years
• Placebo
Tablets, Oral, titration from 75 to 300 mg, once daily up to 6 years

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Corrientes
Argentina	Local Institution	Mendoza
Argentina	Local Institution	Rosario	Santa Fe
Argentina	Local Institution	San Martin	Buenos Aires
Australia	Local Institution	Auchenflower	Queensland
Australia	Local Institution	Brisbane	Queensland
Australia	Local Institution	Coffs Harbour	New South Wales
Australia	Local Institution	Concord	New South Wales
Australia	Local Institution	Garran	New South Wales
Australia	Local Institution	Geelong	Victoria
Australia	Local Institution	Kogarah	New South Wales
Australia	Local Institution	Launceston	Tasmania
Australia	Local Institution	Prahran	Victoria
Australia	Local Institution	Randwick	New South Wales
Australia	Local Institution	Woolloongabba	Queensland
Belgium	Local Institution	Aalst
Belgium	Local Institution	AYE
Belgium	Local Institution	Borgerhout
Belgium	Local Institution	Genk-waterschei
Belgium	Local Institution	Gent
Belgium	Local Institution	Hasselt
Belgium	Local Institution	HUY
Belgium	Local Institution	Leuven
Belgium	Local Institution	Verviers
Brazil	Local Institution	Belo Horizonte	Minas Gerais
Brazil	Local Institution	Campinas	Sao Paulo
Brazil	Local Institution	Goiania-go	Goias
Brazil	Local Institution	Rio de Janeiro
Brazil	Local Institution	Salvador	Bahia
Brazil	Local Institution	Sao Paulo, Sp	Sao Paulo
Canada	Local Institution	Ajax	Ontario
Canada	Local Institution	Calgary	Alberta
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	Longueuil	Quebec
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Rexdale	Ontario
Canada	Local Institution	Scarborough	Ontario
Canada	Local Institution	St-Lambert	Quebec
Canada	Local Institution	Ste-Foy	Quebec
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution	Victoria	British Columbia
Canada	Local Institution	Weston	Ontario
Czech Republic	Local Institution	Prague 2
Czech Republic	Local Institution	Prague 4
Czech Republic	Local Institution	Prague 9
Czech Republic	Local Institution	Usti Nad Labem
Denmark	Local Institution	Copenhagen
Denmark	Local Institution	Copenhagen Nv
France	Local Institution	Abbeville
France	Local Institution	Cholet
France	Local Institution	DAX
France	Local Institution	GAP
France	Local Institution	Langres
France	Local Institution	Lille
France	Local Institution	Montbeliard
France	Local Institution	Paris Cedex 13
France	Local Institution	Poissy
France	Local Institution	Pontoise
France	Local Institution	Provins
France	Local Institution	Roubaix
France	Local Institution	Rouen
France	Local Institution	Saint Malo
France	Local Institution	Tours
France	Local Institution	Vandoeuvre Les Nancy
France	Local Institution	Vichy Cedex
Germany	Local Institution	Bad Homburg
Germany	Local Institution	Berlin
Germany	Local Institution	Goettingen
Germany	Local Institution	Gunzenhausen
Germany	Local Institution	Halle
Germany	Local Institution	Homburg / Saar
Germany	Local Institution	Jena
Germany	Local Institution	Langen
Germany	Local Institution	Leipzig
Germany	Local Institution	Mainz
Germany	Local Institution	Marburg
Germany	Local Institution	Muenchen
Germany	Local Institution	Regensburg
Germany	Local Institution	Stuttgart
Germany	Local Institution	Witten
Germany	Local Institution	Wuerzburg
Greece	Local Institution	Athens
Greece	Local Institution	Patras
Hungary	Local Institution	Budapest
Hungary	Local Institution	Debrecen
Hungary	Local Institution	Siofok
Hungary	Local Institution	Szeged
Ireland	Local Institution	County Dublin	Dublin
Ireland	Local Institution	Dublin
Italy	Local Institution	Ascoli Piceno
Italy	Local Institution	Bologna
Italy	Local Institution	Brescia
Italy	Local Institution	Cosenza
Italy	Local Institution	Pavia
Italy	Local Institution	Perugia
Italy	Local Institution	Piacenza
Italy	Local Institution	Roma
Italy	Local Institution	Siena
Italy	Local Institution	Trieste
Italy	Local Institution	Udine
Mexico	Local Institution	Aguascalientes
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Mexico	Distrito Federal
Mexico	Local Institution	San Pedro Garza Garcia	Nuevo Leon
Netherlands	Local Institution	Alkmaar
Netherlands	Local Institution	Almere
Netherlands	Local Institution	Amersfoort
Netherlands	Local Institution	Apeldoorn
Netherlands	Local Institution	Assen
Netherlands	Local Institution	Breda
Netherlands	Local Institution	Delft
Netherlands	Local Institution	Emmen
Netherlands	Local Institution	Gorinchem
Netherlands	Local Institution	Groningen
Netherlands	Local Institution	Heemstede
Netherlands	Local Institution	Helmond
Netherlands	Local Institution	Hengelo Ov
Netherlands	Local Institution	Nijmegen
Netherlands	Local Institution	Rotterdam
Netherlands	Local Institution	Sittard
Netherlands	Local Institution	Sneek
Netherlands	Local Institution	Veldhoven
Netherlands	Local Institution	Vlaardingen
Netherlands	Local Institution	Zaandam
Norway	Local Institution	Baerum Postterminal
Norway	Local Institution	Stavanger
Norway	Local Institution	Tonsberg
Poland	Local Institution	Bydgoszcz
Poland	Local Institution	Katowice
Poland	Local Institution	Piotrkow Tryb.
Poland	Local Institution	Stalowa Wola
Poland	Local Institution	Warszawa
Poland	Local Institution	Wroclaw
Portugal	Local Institution	Lisbon
Portugal	Local Institution	Matosinhos
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Saratov
Russian Federation	Local Institution	St. Petersburg
South Africa	Local Institution	Berea	Kwa Zulu Natal
South Africa	Local Institution	Congella	Kwa Zulu Natal
South Africa	Local Institution	Johannesburg	Gauteng
South Africa	Local Institution	Morningside	Gauteng
South Africa	Local Institution	Parktown West	Gauteng
Spain	Local Institution	A Coruna
Spain	Local Institution	Barcelona
Spain	Local Institution	Cordoba
Spain	Local Institution	Madrid
Spain	Local Institution	Malaga
Spain	Local Institution	Murcia
Spain	Local Institution	Palma de Mallorca
Spain	Local Institution	Sevilla
Spain	Local Institution	Valencia
Spain	Local Institution	Zaragoza
Sweden	Local Institution	Falun
Sweden	Local Institution	Gothenburg
Sweden	Local Institution	Linkoping
Sweden	Local Institution	Malmo
Sweden	Local Institution	Skelleftea
Sweden	Local Institution	Stockholm
Sweden	Local Institution	Sundsvall
Switzerland	Local Institution	Bellinzona
Switzerland	Local Institution	Liestal
Switzerland	Local Institution	Zuerich
United Kingdom	Local Institution	Dundee
United Kingdom	Local Institution	Glasgow	Dumbartonshire
United Kingdom	Local Institution	Hull	Yorkshire
United Kingdom	Local Institution	Londonderry
United Kingdom	Local Institution	Romford	Essex
United Kingdom	Local Institution	York	Yorkshire
United States	Local Institution	Albany	New York
United States	Local Institution	Albuquerque	New Mexico
United States	Local Institution	Auburn	Maine
United States	Local Institution	Austin	Texas
United States	Local Institution	Birmingham	Alabama
United States	Local Institution	Boston	Massachusetts
United States	Local Institution	Bronx	New York
United States	Local Institution	Canton	Ohio
United States	Local Institution	Chalmette	Louisiana
United States	Local Institution	Chapel Hill	North Carolina
United States	Local Institution	Charleston	South Carolina
United States	Local Institution	Chicago	Illinois
United States	Local Institution	Cincinnati	Ohio
United States	Local Institution	Columbus	Ohio
United States	Local Institution	Concord	North Carolina
United States	Local Institution	Detroit	Michigan
United States	Local Institution	Durham	North Carolina
United States	Local Institution	East Syracuse	New York
United States	Local Institution	Elmer	New Jersey
United States	Local Institution	Farmington	Connecticut
United States	Local Institution	Flourtown	Pennsylvania
United States	Local Institution	Flushing	New York
United States	Local Institution	Germantown	Tennessee
United States	Local Institution	Haverhill	Massachusetts
United States	Local Institution	Jacksonville	Florida
United States	Local Institution	Jacksonville Beach	Florida
United States	Local Institution	Jeffersonville	Indiana
United States	Local Institution	Lake Worth	Florida
United States	Local Institution	Lancaster	Pennsylvania
United States	Local Institution	Lebanon	New Hampshire
United States	Local Institution	Little Rock	Arkansas
United States	Local Institution	Lorain	Ohio
United States	Local Institution	Los Angeles	California
United States	Local Institution	Louisville	Kentucky
United States	Local Institution	Lynchberg	Virginia
United States	Local Institution	Madison	Wisconsin
United States	Local Institution	Minneapolis	Minnesota
United States	Local Institution	Natick	Massachusetts
United States	Local Institution	Omaha	Nebraska
United States	Local Institution	Peoria	Illinois
United States	Local Institution	Peoria	Arizona
United States	Local Institution	Petoskey	Michigan
United States	Local Institution	Portland	Oregon
United States	Local Institution	Reno	Nevada
United States	Local Institution	Richmond	Virginia
United States	Local Institution	Rochester	New York
United States	Local Institution	San Diego	California
United States	Local Institution	San Francisco	California
United States	Local Institution	Sandusky	Ohio
United States	Local Institution	Shreveport	Louisiana
United States	Local Institution	South Boston	Virginia
United States	Local Institution	Spokane	Washington
United States	Local Institution	St. Louis	Missouri
United States	Local Institution	Takoma Park	Maryland
United States	Local Institution	Tampa	Florida
United States	Local Institution	Towson	Maryland
United States	Local Institution	Troy	New York
United States	Local Institution	Tucson	Arizona
United States	Local Institution	Vero Beach	Florida
United States	Local Institution	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Czech Republic,  Denmark,  France,  Germany,  Greece,  Hungary,  Ireland,  Italy,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Russian Federation,  South Africa,  Spain,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (5)

Carson P, Massie BM, McKelvie R, McMurray J, Komajda M, Zile M, Ptaszynska A, Frangin G; I-PRESERVE Investigators. The irbesartan in heart failure with preserved systolic function (I-PRESERVE) trial: rationale and design. J Card Fail. 2005 Oct;11(8):576-8 — View Citation

Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, Anderson S, Donovan M, Iverson E, Staiger C, Ptaszynska A; I-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008 Dec 4;359 — View Citation

McKelvie RS, Komajda M, McMurray J, Zile M, Ptaszynska A, Donovan M, Carson P, Massie BM; I-Preserve Investigators. Baseline plasma NT-proBNP and clinical characteristics: results from the irbesartan in heart failure with preserved ejection fraction trial — View Citation

McMurray JJ, Carson PE, Komajda M, McKelvie R, Zile MR, Ptaszynska A, Staiger C, Donovan JM, Massie BM. Heart failure with preserved ejection fraction: clinical characteristics of 4133 patients enrolled in the I-PRESERVE trial. Eur J Heart Fail. 2008 Feb; — View Citation

Zile MR, Gaasch WH, Anand IS, Haass M, Little WC, Miller AB, Lopez-Sendon J, Teerlink JR, White M, McMurray JJ, Komajda M, McKelvie R, Ptaszynska A, Hetzel SJ, Massie BM, Carson PE; I-Preserve Investigators. Mode of death in patients with heart failure an — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With First Occurrence of the Composite Outcome of Death (All Cause) or Protocol-Specified Cardiovascular (CV) Hospitalization at Given Timepoints	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.	Year 1, Year 2, Year 3, Year 4, Year 5	No
Secondary	Percentage of Participants Experiencing Heart Failure Mortality or Heart Failure Hospitalization at Given Time Points	Treatment comparisons for time to heart failure mortality or heart failure hospitalization	Year 1, Year 2, Year 3, Year 4, Year 5	No
Secondary	Minnesota Living With Heart Failure (MLwHF) Total Score (Sum of Questions 1-21) at Month 6 and 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.	Baseline, Month 6, Month 14	No
Secondary	Minnesota Living With Heart Failure (MLwHF) Total Score (Sum of Questions 1-21) at Final Visit	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.	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.	No
Secondary	Change From Baseline in B-Type Natriuretic Peptide (Pro-BNP) at Month 6 and 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.	Baseline, Month 6, Month 14	Yes
Secondary	Percentage of Participants Experiencing CV Death, Non-Fatal Myocardial Infarction (MI), or Non-Fatal Stroke at Given Timepoints	Treatment comparisons for time to cardiovascular death, non-fatal MI, or non-fatal stroke.	Year 1, Year 2, Year 3, Year 4, Year 5	No
Secondary	Percentage of Participants Experiencing Cardiovascular Death at Given Timepoints	Treatment comparisons for time to cardiovascular death	Year 1, Year 2, Year 3, Year 4, Year 5	No
Secondary	Percentage of Participants Experiencing All-cause Death at Given Time Points	Treatment comparisons for time to all-cause death	Year 1, Year 2, Year 3, Year 4, Year 5	No
Secondary	Change From Baseline in the New York Heart Association (NYHA) Functional Class at Month 6, Month 10, Month 14, and Final Visit	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.	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.	No
Secondary	Physician Assessment of Heart Failure Status at Month 6, Month 14, and Final Visit Compared With Baseline	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.	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.	No
Secondary	Participant Assessment of Heart Failure Status at Month 6, Month 14, and Final Visit Compared With Baseline	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.	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.	No
Secondary	Participant Assessment of Fatigue at Month 6, Month 14, and Final Visit Compared With Baseline	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.	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.	No
Secondary	Participant Assessment of Dyspnea at Month 6, Month 14, and Final Visit Compared With Baseline	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.	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.	No
Secondary	Percentage of Participants Experiencing CV Death or CV Hospitalization at Given Timepoints	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.	Year 1, Year 2, Year 3, Year 4, Year 5	No
Secondary	Percentage of Participants Experiencing Protocol-specified Cardiovascular (CV) Hospitalization at Given Timepoints	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.	Year 1, Year 2, Year 3, Year 4, Year 5	No
Secondary	Percentage of Participants With New Onset of Diabetes Among Subjects With No Prior Diabetes History at Given Timepoints	Treatment comparisons for time to new onset of diabetes (from adverse event reporting) among subjects with no prior history of diabetes.	Year 1, Year 2, Year 3, Year 4, Year 5	Yes
Secondary	Mean Change From Baseline in Glomerular Filtration Rate (GFR) at Month 6, Month 18, and 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.	Baseline, Month 6, Month 18, Month 30	No
Secondary	Mean Change From Baseline in Glomerular Filtration Rate (GFR)at 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.	Baseline, Month 42, Month 54, Month 66	No
Secondary	Number of Participants With New Onset Atrial Fibrillation (AF) Among Those With No Prior AF History or Evidence of AF on Baseline Electrocardiograph (ECG)	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.	Baseline, Final Visit	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm