Impact Of Eplerenone On Cardiovascular Outcomes In Patients Post Myocardial Infarction
- Registration Number
- NCT01176968
- Lead Sponsor
- Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
- Brief Summary
Administration of eplerenone within 24 hours of onset of symptoms of myocardial infarction, in patients without heart failure, reduces cardiovascular mortality / morbidity.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1012
- Subjects must have experienced a myocardial infarction (STEMI) within the previous 24 hours confirmed by symptoms and ECG.
- Subjects with a known low ejection fraction of less than 40% or any previous history of heart failure.
- Subjects treated with eplerenone or other aldosterone antagonists within the past 1 month.
- The subject has uncontrolled hypotension (SBP<90mmHg).
- Subjects with eGFR ≤30ml/min (based on admission serum creatinine and the MDRD formula) or serum creatinine ≥220µmol/L.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Eplerenone plus standard of care Eplerenone - Placebo plus standard of care Placebo Matching placebo for eplerenone 25mg film coated tablets.
- Primary Outcome Measures
Name Time Method First Event of Cardiovascular Mortality, Re-hospitalization or Extended Initial Hospital Stay Due to Diagnosis of Heart Failure, Sustained Ventricular Tachycardia or Fibrillation, Ejection Fraction ≤40% or BNP Above Age Adjusted Cut Off 0-24 months Cardiovascular mortality is defined as any mortality adjudicated as death due to sudden cardiac death, myocardial infarction (MI), worsening heart failure, cardiac arrhythmia, other cause (such as pulmonary embolism, peripheral arterial disease \[PAD\], etc.). Hospitalization due to congestive heart failure (CHF) and requires extended hospital stay or frequent visits to emergency room, observation unit or in-patient care, due to CHF as the primary or secondary diagnosis supported by a discharge report or clinical summary for hospitalization as determined by the endpoint adjudication committee (EAC). A composite of time to first event of cardiovascular mortality (CV), re-hospitalization or extended initial hospital stay due to diagnosis of heart failure, sustained ventricular tachycardia or fibrillation, ejection fraction ≤40% after 1 month or BNP \>200 pg/mL or NT-proBNP \>450 pg/mL (age \<50 years); \>900 pg/mL (age 50 to 75 years) or \>1800 pg/mL (age \>75 years) after 1 month.
- Secondary Outcome Measures
Name Time Method Diagnosis of Heart Failure 0-24 months The occurrence of first diagnosis of heart failure from the date of randomization. Time-to-event analyses were measured from the date of randomization, and a subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence.
Brain (B-type) Natriuretic Peptide (BNP) >200 pg/mL or NT-proBNP >450, >900 or >1800 pg/mL for Ages <50 Years, 50-75 Years and >75 Years, Respectively (Recorded 1 Month or Later Post-randomization). 0-24 months The occurrence of first occurrence of BNP \>200 pg/mL or NT-proBNP \>450, \>900 or \>1800 pg/mL for ages \<50 years, 50 to 75 years and \>75 years, respectively (recorded 28 days or later post-randomization). Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence.
Electrocardiogram Q Wave to the End of the S Wave Corresponding to Ventricle Depolarization (QRS) Duration at 6 Months Post-randomization. 6 months Electrocardiogram Q wave to the end of the S wave corresponding to ventricle depolarization (QRS) duration at 6 months post-randomization. The continuous endpoints were assessed using analysis of covariance (ANCOVA) model, fitted with corresponding baseline and treatment. These were analyzed at 6 months based on last observation carried forward (LOCF) and also using all available data up to end of study.
Cardiovascular Mortality 0-24 months The occurrence of cardiovascular mortality from randomization. Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence.
Change in Serum Levels of Biomarkers (PIIINP, Galectin 3, and PINP) at 6 Months Post-randomization. 6 months Change in serum levels of PIIINP, Galectin 3, and PINP at 6 months post-randomization. The continuous endpoints were assessed using ANCOVA model, fitted with corresponding baseline and treatment. These were analyzed at 6 months based on LOCF and also using all available data up to end of study.
First and Each Subsequent Episode (After an Event Free Interval of ≥ 48 Hours) of Sustained Ventricular Tachycardia or Ventricular Fibrillation. 0-24 months The occurrence of first and each subsequent episode (after an event-free interval of ≥ 48 hours) of sustained ventricular tachycardia or ventricular fibrillation. Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence.
First Recorded Ejection Fraction (EF) of ≤40% (Recorded 1 Month or Later Post-randomization). 0-24 months The occurrence of first recorded EF ≤40% (recorded 28 days or later post-randomization). Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence.
Change in Serum Level of Biomarker (Interleukin-6) at 6 Months Post-randomization. 6 months Change in serum level of Interleukin-6 at 6 months post-randomization. The continuous endpoint was assessed using ANCOVA model, fitted with corresponding baseline and treatment. It was analyzed at 6 months based on LOCF and also using all available data up to end of study.
Decision to Provide an Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT). 0-24 months The decision to provide an ICD or CRT. Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence.
Second or Subsequent Non-fatal Myocardial Infarction (MI). 0-24 months The occurrence of second or subsequent nonfatal MI. Time-to-event analyses were measured from the date of randomization. A subject who did not experience the endpoint(s) of interest was censored on the last day the subject was confirmed by the investigator to be endpoint-free. The time-to-event distributions were summarized by treatment group using Kaplan-Meier estimates of cumulative incidence.
Left Atrial Diameter (LAD) (Recorded on Each Occasion an Echocardiogram is Conducted). 0-24 months LAD recorded each time an echocardiogram is conducted. The continuous endpoints were assessed using ANCOVA model, fitted with corresponding baseline and treatment. These were analyzed at 6 months based on LOCF and also using all available data up to end of study.
Change in Serum Levels of Biomarkers (Aldosterone and Cortisol) at 6 Months Post-randomization. 6 months Change in serum levels of aldosterone and cortisol at 6 months post-randomization. The continuous endpoints were assessed using ANCOVA model, fitted with corresponding baseline and treatment. These were analyzed at 6 months based on LOCF and also using all available data up to end of study.
Change in Serum Level of Biomarker (ICTP) at 6 Months Post-randomization. 6 months Change in serum level of ICTP at 6 months post-randomization. The continuous endpoint was assessed using ANCOVA model, fitted with corresponding baseline and treatment. It was analyzed at 6 months based on LOCF and also using all available data up to end of study.
Trial Locations
- Locations (74)
Univerzitna nemocnica Martin
🇸🇰Martin, Slovakia
Vseobecna nemocnica Rimavska Sobota
🇸🇰Rimavska Sobota, Slovakia
Kardiocentrum Nitra, s.r.o.
🇸🇰Nitra, Slovakia
Narodny ustav srdcovych a cievnych chorob, a.s.
🇸🇰Bratislava, Slovakia
Health Sciences Center, Eastern Health
🇨🇦St. John's, Newfoundland and Labrador, Canada
Vancouver General Hospital, Vancouver Coastal Health Authority
🇨🇦Vancouver, British Columbia, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Vancouver General Hospital - Centennial Pavilion
🇨🇦Vancouver, British Columbia, Canada
Walter C Mackenzie Health Sciences Centre (WCM)
🇨🇦Edmonton, Alberta, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier Universitaire de Sherbrooke, Hopital Fleurimont
🇨🇦Sherbrooke, Quebec, Canada
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Nemocnice Na Homolce - kardiologicke oddeleni
🇨🇿Praha 5, Czechia
Chu Rangueil Service de Cardiologie, A - Bat H1
🇫🇷Toulouse, Cedex 4, France
Chu du Bocage - Centre de Cardiologie
🇫🇷Dijon, Cedex, France
Hopital De La Pitie Salpetriere
🇫🇷Paris, Cedex, France
Hôpital Henri Mondor
🇫🇷Creteil, France
Academic cardiology Unit
🇬🇧Cottingham Hull, United Kingdom
Centre de Cardiologie d'Evecquemont
🇫🇷Evecquemont, France
Ninewells Hospital and Medical School
🇬🇧Dundee, United Kingdom
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
🇩🇪Mainz, Germany
Medizinische Fakultaet Carl Gustav Carus Technische Universitaet Dresden
🇩🇪Dresden, Germany
St. Vincenz Krankenhaus
🇩🇪Limburg, Germany
Edinburgh Royal Infirmary
🇬🇧Edinburgh, Lothian, United Kingdom
Cardiologie Interventionnelle
🇫🇷Pessac Cedex, France
Clinical Trials Unit Morriston Hospital
🇬🇧Swansea, Wales, United Kingdom
The Queens Medical Research Institute- University of Edinburgh
🇬🇧Edinburgh, United Kingdom
City Hospital
🇬🇧Birmingham, United Kingdom
Charite - Universitaetsmedizin Berlin
🇩🇪Berlin, Germany
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Blackpool Victoria Hospital NHS Trust , Cardiac Research ,Lancashire Cardiac Centre
🇬🇧Blackpool, Lancashire, United Kingdom
Klinikum Links der Weser gGmbH
🇩🇪Bremen, Germany
University General Hospital of Patra
🇬🇷Rio Patra, Greece
Onze Lieve Vrouwe Gasthuis, Locatie Oosterpark
🇳🇱Amsterdam, Netherlands
Hospital Universitari Son Espases
🇪🇸Palma de Mallorca, Spain
University Hospital of Leicester (UHL) NHS Trust
🇬🇧Leicester, United Kingdom
Service Cardiologie, Centre Hospitalier de Cannes
🇫🇷Cannes, France
Clinical Trials Unit, Morriston Hospital
🇬🇧Swansea, United Kingdom
Georg-August-Universitaet Goettingen, Zentrum f. Innere Medizin / Kardiologie u. Pneumologie
🇩🇪Goettingen, Germany
Zala Megyei Korhaz, Kardiologia
🇭🇺Zalaegerszeg, Hungary
Budai Irgalmasrendi Korhaz, Kardiologia
🇭🇺Budapest, Hungary
Diamond Health Care Centre (DHCC)
🇨🇦Vancouver, British Columbia, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Centre de Sante et de Services Sociaux de Chicoutimi (CSSSC) (Complexe Hospitalier de la Sagamie)
🇨🇦Chicoutimi, Quebec, Canada
ECOGENE-21 / Centre de sante et de services sociaux de Chicoutimi
🇨🇦Chicoutimi, Quebec, Canada
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
I.Interni klinika-kardiologie FN Olomouc
🇨🇿Olomouc, Czechia
I. Interni klinika - kardiologie FN Olomouc
🇨🇿Olomouc, Czechia
Klinika kardiologie IKEM
🇨🇿Praha 4, Czechia
Universitaets-Herzzentrum Freiburg Bad Krozingen
🇩🇪Bad Krozingen, Germany
Hôpital Henri Mondor - Pysiologie explorations fonctionnelles
🇫🇷Creteil, France
Sankt Johannes Hospital Medizinische Klinik I
🇩🇪Dortmund, Germany
Service Cardiologie Hopital Robert Boulin
🇫🇷Libourne, France
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitaeres Herzzentrum Hamburg
🇩🇪Hamburg, Germany
Sankt Johannes Hospital
🇩🇪Dortmund, Germany
General Hospital of Athens "Georgios Gennimatas"
🇬🇷Athens, Greece
Staedtisches Klinikum Muenchen GmbH Klinikum Neuperlach
🇩🇪Munich, Germany
Petz Aladar Megyei Oktato Korhaz, Kardiologiai Osztaly
🇭🇺Gyor, Hungary
General Hospital of Attiki KAT
🇬🇷Athens, Greece
Josa Andras Oktato Korhaz Egeszsegugyi Szolgaltato Nonprofit Kft., Kardiologia
🇭🇺Nyiregyhaza, Hungary
St. Antonius Ziekenhuis
🇳🇱Nieuwegein, Netherlands
Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii NZOZ w Oswiecimiu G.V.M CARINT Sp. zo.o.
🇵🇱Oswiecim, Poland
Stredoslovensky ustav srdcovych a cievnych chorob, a.s.
🇸🇰Banska Bystrica, Slovakia
Oddzial Kardiologiczny Wojewodzki Szpital Specjalistyczny We Wroclawiu
🇵🇱Wroclaw, Poland
Hospital Del Sas de Jerez de La Frontera
🇪🇸Jerez de la Frontera, Cadiz, Spain
Hospital del Mar.
🇪🇸Barcelona, Spain
"Hospital Clinic i Provincial de Barcelona,Instituto Clinic del Torax
🇪🇸Barcelona, Spain
Hospital Universitario de La Paz
🇪🇸Madrid, Spain
HOSPITAL CLINICO SAN CARLOS- Universidad Complutense de Madrid
🇪🇸Madrid, Spain
Oddzial Kardiologiczny Wojewodzki Szpital Specjalistyczny w Olsztynie
🇵🇱Olsztyn, Poland
Katedra i Klinika Kardiologii i Chorob Wewnetrznych
🇵🇱Bydgoszcz, Poland
University Hospitals Coventry and Warwickshire NHS Trust
🇬🇧Coventry, United Kingdom