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Trial record 1 of 1 for:    NCT01176968
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Impact Of Eplerenone On Cardiovascular Outcomes In Patients Post Myocardial Infarction (REMINDER)

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ClinicalTrials.gov Identifier: NCT01176968
Recruitment Status : Completed
First Posted : August 6, 2010
Results First Posted : August 15, 2016
Last Update Posted : December 22, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )

Tracking Information
First Submitted Date  ICMJE August 4, 2010
First Posted Date  ICMJE August 6, 2010
Results First Submitted Date  ICMJE October 18, 2013
Results First Posted Date  ICMJE August 15, 2016
Last Update Posted Date December 22, 2020
Study Start Date  ICMJE September 2010
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 1, 2016)
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 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 4, 2010)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2016)
  • Cardiovascular Mortality [ Time Frame: 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.
  • Diagnosis of Heart Failure [ Time Frame: 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.
  • 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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 4, 2010)
  • Time to cardiovascular mortality [ Time Frame: 0-18 months ]
  • Time to diagnosis of heart failure [ Time Frame: 0-18 months ]
  • 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 ]
  • Time to first recorded ejection fraction of ≤ 40% (recorded 1 month or later post-randomization). [ Time Frame: 0-18 months ]
  • 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 ]
  • Time to decision to provide an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT). [ Time Frame: 0-18 months ]
  • Time to second or subsequent non-fatal myocardial infarction. [ Time Frame: 0-'18 months ]
  • QRS duration at 6 months post-randomization. [ Time Frame: 6 months ]
  • Left atrial diameter (recorded on each occasion an echocardiogram is conducted). [ Time Frame: 0-18 months ]
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Impact Of Eplerenone On Cardiovascular Outcomes In Patients Post Myocardial Infarction
Official Title  ICMJE A Double-blind, Randomized, Placebo-controlled Trial Evaluating The Safety And Efficacy Of Early Treatment With Eplerenone In Patients With Acute Myocardial Infarction
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Myocardial Infarction
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * 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.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 1, 2016)
1012
Original Estimated Enrollment  ICMJE
 (submitted: August 4, 2010)
612
Actual Study Completion Date  ICMJE October 2012
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Czechia,   France,   Germany,   Greece,   Hungary,   Netherlands,   Poland,   Slovakia,   Spain,   United Kingdom
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01176968
Other Study ID Numbers  ICMJE A6141116
2010-019844-38 ( EudraCT Number )
REMINDER ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )
Study Sponsor  ICMJE Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date December 2020

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