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Impact Of Eplerenone On Cardiovascular Outcomes In Patients Post Myocardial Infarction (REMINDER)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01176968
First received: August 4, 2010
Last updated: July 1, 2016
Last verified: July 2016
  Purpose
Administration of eplerenone within 24 hours of onset of symptoms of myocardial infarction, in patients without heart failure, reduces cardiovascular mortality / morbidity.

Condition Intervention Phase
Myocardial Infarction
Drug: Eplerenone
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Double-blind, Randomized, Placebo-controlled Trial Evaluating The Safety And Efficacy Of Early Treatment With Eplerenone In Patients With Acute Myocardial Infarction

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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 [ Time Frame: 0-24 months ] [ Designated as safety issue: No ]
    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:
  • Cardiovascular Mortality [ Time Frame: 0-24 months ] [ Designated as safety issue: No ]
    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.

  • Diagnosis of Heart Failure [ Time Frame: 0-24 months ] [ Designated as safety issue: No ]
    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.

  • First and Each Subsequent Episode (After an Event Free Interval of ≥ 48 Hours) of Sustained Ventricular Tachycardia or Ventricular Fibrillation. [ Time Frame: 0-24 months ] [ Designated as safety issue: No ]
    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). [ Time Frame: 0-24 months ] [ Designated as safety issue: No ]
    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.

  • 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). [ Time Frame: 0-24 months ] [ Designated as safety issue: No ]
    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.

  • Decision to Provide an Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT). [ Time Frame: 0-24 months ] [ Designated as safety issue: No ]
    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). [ Time Frame: 0-24 months ] [ Designated as safety issue: No ]
    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.

  • Electrocardiogram Q Wave to the End of the S Wave Corresponding to Ventricle Depolarization (QRS) Duration at 6 Months Post-randomization. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.

  • Left Atrial Diameter (LAD) (Recorded on Each Occasion an Echocardiogram is Conducted). [ Time Frame: 0-24 months ] [ Designated as safety issue: No ]
    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. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 Levels of Biomarkers (PIIINP, Galectin 3, and PINP) at 6 Months Post-randomization. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.

  • Change in Serum Level of Biomarker (ICTP) at 6 Months Post-randomization. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.

  • Change in Serum Level of Biomarker (Interleukin-6) at 6 Months Post-randomization. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 1012
Study Start Date: September 2010
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eplerenone plus standard of care Drug: Eplerenone
Maximum dose of 2x25 mg film coated tablets per day for the duration of the study (approximately 18 months maximum). Lower doses may be administered determined by blood biochemistry data.
Other Name: Inspra
Placebo Comparator: Placebo plus standard of care
Matching placebo for eplerenone 25mg film coated tablets.
Drug: Placebo
Matching placebo tablets

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have experienced a myocardial infarction (STEMI) within the previous 24 hours confirmed by symptoms and ECG.

Exclusion Criteria:

  • 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.
  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: NCT01176968

  Hide Study Locations
Locations
Canada, Alberta
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2B7
Walter C Mackenzie Health Sciences Centre (WCM)
Edmonton, Alberta, Canada, T6G 2B7
Canada, British Columbia
Diamond Health Care Centre (DHCC)
Vancouver, British Columbia, Canada, V5Z 1M9
Vancouver General Hospital - Centennial Pavilion
Vancouver, British Columbia, Canada, V5Z 1M9
Vancouver General Hospital, Vancouver Coastal Health Authority
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Newfoundland and Labrador
Health Sciences Center, Eastern Health
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Ontario
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
St. Michael's Hospital
Toronto, Ontario, Canada, M5B1W8
Canada, Quebec
Centre de Sante et de Services Sociaux de Chicoutimi (CSSSC) (Complexe Hospitalier de la Sagamie)
Chicoutimi, Quebec, Canada, G7H 5H6
ECOGENE-21 / Centre de sante et de services sociaux de Chicoutimi
Chicoutimi, Quebec, Canada, G7H 7P2
Centre Hospitalier Universitaire de Sherbrooke, Hopital Fleurimont
Sherbrooke, Quebec, Canada, J1H 5N4
Czech Republic
Fakultni nemocnice Brno
Brno, Czech Republic, 62500
Fakultni nemocnice Hradec Kralove
Hradec Kralove, Czech Republic, 500 05
Fakultni nemocnice Hradec Kralove
Hradec Kralove, Czech Republic, 50005
I.Interni klinika-kardiologie FN Olomouc
Olomouc, Czech Republic, 775 20
I. Interni klinika - kardiologie FN Olomouc
Olomouc, Czech Republic, 77520
Klinika kardiologie IKEM
Praha 4, Czech Republic, 140 21
Nemocnice Na Homolce - kardiologicke oddeleni
Praha 5, Czech Republic, 150 30
France
Chu Rangueil Service de Cardiologie, A - Bat H1
Toulouse, Cedex 4, France, 31403
Chu du Bocage - Centre de Cardiologie
Dijon, Cedex, France, 21034
Hopital De La Pitie Salpetriere
Paris, Cedex, France, 75013
Service Cardiologie, Centre Hospitalier de Cannes
Cannes, France, 06401
Hôpital Henri Mondor - Pysiologie explorations fonctionnelles
Creteil, France, 94010
Hôpital Henri Mondor
Creteil, France, 94010
Centre de Cardiologie d'Evecquemont
Evecquemont, France, 78740
Service Cardiologie Hopital Robert Boulin
Libourne, France, 33500
Cardiologie Interventionnelle
Pessac Cedex, France, 33604
Germany
Universitaets-Herzzentrum Freiburg Bad Krozingen
Bad Krozingen, Germany, 79189
Charite - Universitaetsmedizin Berlin
Berlin, Germany, 12200
Universitätsklinikum Bonn
Bonn, Germany, 53127
Klinikum Links der Weser gGmbH
Bremen, Germany, 28277
Sankt Johannes Hospital Medizinische Klinik I
Dortmund, Germany, 44137
Sankt Johannes Hospital
Dortmund, Germany, 44137
Medizinische Fakultaet Carl Gustav Carus Technische Universitaet Dresden
Dresden, Germany, 01309
Georg-August-Universitaet Goettingen, Zentrum f. Innere Medizin / Kardiologie u. Pneumologie
Goettingen, Germany, 37075
Universitaeres Herzzentrum Hamburg
Hamburg, Germany, 20246
Medizinische Hochschule Hannover
Hannover, Germany, 30625
St. Vincenz Krankenhaus
Limburg, Germany, 65549
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz, Germany, 55131
Staedtisches Klinikum Muenchen GmbH Klinikum Neuperlach
Munich, Germany, 81737
Greece
General Hospital of Athens "Georgios Gennimatas"
Athens, Greece, 11527
General Hospital of Attiki KAT
Athens, Greece, 14561
University General Hospital of Patra
Rio Patra, Greece, 26500
Hungary
Budai Irgalmasrendi Korhaz, Kardiologia
Budapest, Hungary, 1027
Petz Aladar Megyei Oktato Korhaz, Kardiologiai Osztaly
Gyor, Hungary, 9024
Josa Andras Oktato Korhaz Egeszsegugyi Szolgaltato Nonprofit Kft., Kardiologia
Nyiregyhaza, Hungary, 4400
Zala Megyei Korhaz, Kardiologia
Zalaegerszeg, Hungary, 8900
Netherlands
Onze Lieve Vrouwe Gasthuis, Locatie Oosterpark
Amsterdam, Netherlands, 1091 AC
St. Antonius Ziekenhuis
Nieuwegein, Netherlands, 3435 CM
Poland
Katedra i Klinika Kardiologii i Chorob Wewnetrznych
Bydgoszcz, Poland, 85-094
Oddzial Kardiologiczny Wojewodzki Szpital Specjalistyczny w Olsztynie
Olsztyn, Poland, 10-561
Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii NZOZ w Oswiecimiu G.V.M CARINT Sp. zo.o.
Oswiecim, Poland, 32-600
Oddzial Kardiologiczny Wojewodzki Szpital Specjalistyczny We Wroclawiu
Wroclaw, Poland, 51-124
Slovakia
Stredoslovensky ustav srdcovych a cievnych chorob, a.s.
Banska Bystrica, Slovakia, 974 01
Narodny ustav srdcovych a cievnych chorob, a.s.
Bratislava, Slovakia, 833 48
Univerzitna nemocnica Martin
Martin, Slovakia, 036 59
Kardiocentrum Nitra, s.r.o.
Nitra, Slovakia, 949 01
Vseobecna nemocnica Rimavska Sobota
Rimavska Sobota, Slovakia, 979 12
Spain
Hospital Del Sas de Jerez de La Frontera
Jerez de la Frontera, Cadiz, Spain, 11407
"Hospital Clinic i Provincial de Barcelona,Instituto Clinic del Torax
Barcelona, Spain, 08036
Hospital del Mar.
Barcelona, Spain, 8003
HOSPITAL CLINICO SAN CARLOS- Universidad Complutense de Madrid
Madrid, Spain, 28040
Hospital Universitario de La Paz
Madrid, Spain, 28046
Hospital Universitari Son Espases
Palma de Mallorca, Spain, 07010
Hospital General Universitario de Valencia
Valencia, Spain, 46014
United Kingdom
Blackpool Victoria Hospital NHS Trust , Cardiac Research ,Lancashire Cardiac Centre
Blackpool, Lancashire, United Kingdom, FY3 8NR
Edinburgh Royal Infirmary
Edinburgh, Lothian, United Kingdom, EH16 4SA
Clinical Trials Unit Morriston Hospital
Swansea, Wales, United Kingdom, SA6 6NL
City Hospital
Birmingham, United Kingdom, B18 7QH
Academic cardiology Unit
Cottingham Hull, United Kingdom, HU16 5JQ
University Hospitals Coventry and Warwickshire NHS Trust
Coventry, United Kingdom, CV2 2DX
Ninewells Hospital and Medical School
Dundee, United Kingdom, DD1 9SY
The Queens Medical Research Institute- University of Edinburgh
Edinburgh, United Kingdom, EH16 4TJ
University Hospital of Leicester (UHL) NHS Trust
Leicester, United Kingdom, LE3 GQP
Clinical Trials Unit, Morriston Hospital
Swansea, United Kingdom, SA6 6NL
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01176968     History of Changes
Other Study ID Numbers: A6141116  2010-019844-38  REMINDER 
Study First Received: August 4, 2010
Results First Received: October 18, 2013
Last Updated: July 1, 2016
Health Authority: Canada: Health Canada

Keywords provided by Pfizer:
Eplerenone
myocardial infarction
mortality
morbidity

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Eplerenone
Spironolactone
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents

ClinicalTrials.gov processed this record on December 06, 2016