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

August 4, 2010
July 1, 2016
September 2010
October 2012   (final data collection date for primary outcome measure)
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.
Time to first event of cardiovascular mortality, re-hospitalization or extended initial hospital stay due to diagnosis of heart failure, sustained ventricular tachycardia or fibrillation. [ Time Frame: 0-18 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01176968 on ClinicalTrials.gov Archive Site
  • 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.
  • Time to cardiovascular mortality [ Time Frame: 0-18 months ] [ Designated as safety issue: No ]
  • Time to diagnosis of heart failure [ Time Frame: 0-18 months ] [ Designated as safety issue: No ]
  • Time to first and each subsequent episode (after an event free interval of ≥ 48 hours) of sustained ventricular tachycardia or ventricular fibrillation. [ Time Frame: 0-18 months ] [ Designated as safety issue: No ]
  • Time to first recorded ejection fraction of ≤ 40% (recorded 1 month or later post-randomization). [ Time Frame: 0-18 months ] [ Designated as safety issue: No ]
  • Time to 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: 0-18 months ] [ Designated as safety issue: No ]
  • Time to decision to provide an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT). [ Time Frame: 0-18 months ] [ Designated as safety issue: No ]
  • Time to second or subsequent non-fatal myocardial infarction. [ Time Frame: 0-`18 months ] [ Designated as safety issue: No ]
  • QRS duration at 6 months post-randomization. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Left atrial diameter (recorded on each occasion an echocardiogram is conducted). [ Time Frame: 0-18 months ] [ Designated as safety issue: No ]
  • Change in serum levels of biomarkers at 6 months post-randomization. Blood samples for biomarkers will be stored and analyzed post completion of the study. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Impact Of Eplerenone On Cardiovascular Outcomes In Patients Post Myocardial Infarction
A Double-blind, Randomized, Placebo-controlled Trial Evaluating The Safety And Efficacy Of Early Treatment With Eplerenone In Patients With Acute Myocardial Infarction
Administration of eplerenone within 24 hours of onset of symptoms of myocardial infarction, in patients without heart failure, reduces cardiovascular mortality / morbidity.
Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Myocardial Infarction
  • 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
  • Drug: Placebo
    Matching placebo tablets
  • Experimental: Eplerenone plus standard of care
    Intervention: Drug: Eplerenone
  • Placebo Comparator: Placebo plus standard of care
    Matching placebo for eplerenone 25mg film coated tablets.
    Intervention: Drug: Placebo
Montalescot G, Pitt B, Lopez de Sa E, Hamm CW, Flather M, Verheugt F, Shi H, Turgonyi E, Orri M, Vincent J, Zannad F; REMINDER Investigators; REMINDER Investigators. Early eplerenone treatment in patients with acute ST-elevation myocardial infarction without heart failure: the Randomized Double-Blind Reminder Study. Eur Heart J. 2014 Sep 7;35(34):2295-302. doi: 10.1093/eurheartj/ehu164. Epub 2014 Apr 29.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1012
October 2012
October 2012   (final data collection date for primary outcome measure)

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.
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   Czech Republic,   France,   Germany,   Greece,   Hungary,   Netherlands,   Poland,   Slovakia,   Spain,   United Kingdom
 
NCT01176968
A6141116, 2010-019844-38, REMINDER
Yes
Not Provided
Not Provided
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP