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Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01764633
Recruitment Status : Completed
First Posted : January 9, 2013
Results First Posted : February 15, 2018
Last Update Posted : March 8, 2023
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE January 8, 2013
First Posted Date  ICMJE January 9, 2013
Results First Submitted Date  ICMJE December 15, 2017
Results First Posted Date  ICMJE February 15, 2018
Last Update Posted Date March 8, 2023
Actual Study Start Date  ICMJE February 8, 2013
Actual Primary Completion Date November 11, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2018)		 Time to Cardiovascular Death, Myocardial Infarction, Hospitalization for Unstable Angina, Stroke, or Coronary Revascularization [ Time Frame: Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported. ]
All deaths and potential endpoint events were adjudicated by an independent external Clinical Events Committee (CEC) led by the Thrombolysis in Myocardial Infarction (TIMI) Study Group, using standardized definitions based on the "Standardized Definitions for Cardiovascular and Stroke End Point Events in Clinical Trials and the Third Universal Definition of Myocardial Infarction". Time to cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization was defined as the time from randomization to the first occurrence of any component of the composite endpoint and was analyzed using Kaplan-Meier (KM) survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on last non-fatal potential endpoint collection date.
Original Primary Outcome Measures  ICMJE
 (submitted: January 8, 2013)		 Time to cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke, or coronary revascularization [ Time Frame: 5 years ]
The primary endpoint is the time to cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke, or coronary revascularization, whichever occurs first.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2018)
  • Time to Cardiovascular Death, Myocardial Infarction, or Stroke [ Time Frame: Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported. ]
    All deaths and potential endpoint events were adjudicated by an independent external CEC led by the TIMI Study Group, using standardized definitions based on the "Standardized Definitions for Cardiovascular and Stroke End Point Events in Clinical Trials and the Third Universal Definition of Myocardial Infarction". Time to cardiovascular death, myocardial infarction, or stroke was defined as the time from randomization to the first occurrence of any component of the composite endpoint and was analyzed using Kaplan-Meier (KM) survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on last non-fatal potential endpoint collection date.
  • Time to Cardiovascular Death [ Time Frame: Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported. ]
    All deaths and potential endpoint events were adjudicated by an independent external CEC led by the TIMI Study Group, using standardized definitions based on the "Standardized Definitions for Cardiovascular and Stroke End Point Events in Clinical Trials and the Third Universal Definition of Myocardial Infarction". Cardiovascular death includes death resulting from an acute myocardial infarction (MI), sudden cardiac death, death due to heart failure (HF), death due to stroke, death due to cardiovascular (CV) procedures, death due to CV hemorrhage, and death due to other CV causes. Time to cardiovascular death was defined as the time from randomization to the date of cardiovascular death and was analyzed using Kaplan-Meier (KM) survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on the last confirmed survival status date.
  • Time to All Cause Death [ Time Frame: Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported. ]
    Time to all-cause death was defined as the time from randomization to the date of death and was analyzed using Kaplan-Meier (KM) survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on the last confirmed survival status date.
  • Time to First Myocardial Infarction [ Time Frame: Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported. ]
    All deaths and potential endpoint events were adjudicated by an independent external CEC led by the TIMI Study Group, using standardized definitions based on the "Standardized Definitions for Cardiovascular and Stroke End Point Events in Clinical Trials and the Third Universal Definition of Myocardial Infarction". The diagnosis of myocardial infarction required the combination of:
    • Evidence of myocardial necrosis (either changes in cardiac biomarkers or post-mortem pathological findings); and
    • Supporting information derived from the clinical presentation, electrocardiographic changes, or the results of myocardial or coronary artery Imaging.
    Time to first myocardial infarction was defined as the time from randomization to the date of the first MI and was analyzed using Kaplan-Meier survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on last non-fatal potential endpoint collection date.
  • Time to First Stroke [ Time Frame: Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported. ]
    All deaths and potential endpoint events were adjudicated by an independent external CEC led by the TIMI Study Group, using standardized definitions based on the "Standardized Definitions for Cardiovascular and Stroke End Point Events in Clinical Trials and the Third Universal Definition of Myocardial Infarction". Stroke was defined as an acute episode of focal or global neurological dysfunction caused by brain, spinal cord, or retinal vascular injury as a result of hemorrhage or infarction. Time to first stroke was defined as the time from randomization to the date of the stroke and was analyzed using Kaplan-Meier (KM) survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on last non-fatal potential endpoint collection date.
  • Time to First Coronary Revascularization [ Time Frame: Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported. ]
    All deaths and potential endpoint events were adjudicated by an independent external CEC led by the TIMI Study Group, using standardized definitions based on the "Standardized Definitions for Cardiovascular and Stroke End Point Events in Clinical Trials and the Third Universal Definition of Myocardial Infarction". Time to first coronary revascularization was defined as the time from randomization to the date of the coronary revascularization and was analyzed using Kaplan-Meier (KM) survival analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on last non-fatal potential endpoint collection date.
  • Time to Cardiovascular Death or First Hospitalization for Worsening Heart Failure [ Time Frame: Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported. ]
    All events were adjudicated by an independent external CEC led by the TIMI Study Group, using standardized definitions. HF hospitalization was defined as an event that met all of the following criteria:
    1. Admitted to hospital with a primary diagnosis of HF
    2. In hospital for at least 24 hours
    3. Documented new or worsening symptoms due to HF, including at least 1 of the following:
      • Dyspnea
      • Decreased exercise tolerance
      • Fatigue
      • Other symptoms of worsened end-organ perfusion or volume overload
    4. Evidence of new or worsening HF consisting of at least 2 physical exam findings or 1 physical exam finding and at least 1 laboratory criterion
    5. Received new or increased treatment for HF. Time to CV death or first hospitalization for worsening HF was defined as the time from randomization to the first occurrence of any component of the endpoint analyzed using KM survival analysis. Participants with no event were censored based on last non-fatal potential endpoint collection date.
  • Time to First Ischemic Fatal or Non-Fatal Stroke or Transient Ischemic Attack [ Time Frame: Events that occurred from randomization to the last confirmed survival status date; the median duration of follow-up was 26 months. KM estimates at 6, 12, 18, 24, 30 and 36 months are reported. ]
    All deaths and potential endpoint events were adjudicated by an independent external CEC led by the TIMI Study Group, using standardized definitions. Ischemic stroke was defined as an acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of central nervous system tissue. Transient ischemic attack (TIA) was defined as a transient episode of focal neurological dysfunction caused by brain, spinal cord, or retinal ischemia, without acute infarction. Time to first ischemic fatal or non-fatal stroke or TIA was defined as the time from randomization to the first occurrence of any component of the composite endpoint and was analyzed using KM analysis. KM estimates of the percentage of participants with an event are reported. Participants with no event were censored based on last non-fatal potential endpoint collection date.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2013)
  • Time to cardiovascular death, myocardial infarction, or stroke [ Time Frame: 5 years ]
    Time to cardiovascular death, myocardial infarction, or stroke, whichever occurs first
  • Time to death by any cause [ Time Frame: 5 years ]
    Time to death by any cause
  • Time to cardiovascular death or hospitalization for worsening heart failure [ Time Frame: 5 years ]
    Time to cardiovascular death or hospitalization for worsening heart failure, whichever occurs first
  • Time to ischemic fatal or non-fatal stroke or TIA [ Time Frame: 5 years ]
    Time to ischemic fatal or non-fatal stroke or TIA, whichever occurs first
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk
Official Title  ICMJE A Double-blind, Randomized, Placebo-controlled, Multicenter Study Assessing the Impact of Additional LDL-Cholesterol Reduction on Major Cardiovascular Events When Evolocumab (AMG 145) is Used in Combination With Statin Therapy In Patients With Clinically Evident Cardiovascular Disease
Brief Summary The primary objective was to evaluate the effect of treatment with evolocumab, compared with placebo, on the risk for cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization, whichever occurs first, in patients with clinically evident cardiovascular disease.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Dyslipidemia
Intervention  ICMJE
  • Biological: Evolocumab
    Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.
    Other Names:
    • AMG 145
    • Repatha
  • Drug: Placebo
    Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference.
    Intervention: Drug: Placebo
  • Experimental: Evolocumab
    Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference.
    Intervention: Biological: Evolocumab
Publications *

*   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: June 25, 2015)		 27564
Original Estimated Enrollment  ICMJE
 (submitted: January 8, 2013)		 22500
Actual Study Completion Date  ICMJE November 11, 2016
Actual Primary Completion Date November 11, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female ≥ 40 to ≤ 85 years of age
  • History of clinically evident cardiovascular disease at high risk for a recurrent event
  • Fasting low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dL (≥ 1.8 mmol/L) ) or non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 100 mg/dL (> 2.6 mmol/L)
  • Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

Exclusion Criteria:

  • New York Heart Association (NYHA) class III or IV, or last known left ventricular ejection fraction < 30%
  • Uncontrolled hypertension
  • Uncontrolled or recurrent ventricular tachycardia
  • Untreated hyperthyroidism or hypothyroidism
  • Homozygous familial hypercholesterolemia
  • LDL or plasma apheresis
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 85 Years   (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 Argentina,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Colombia,   Czechia,   Denmark,   Estonia,   Finland,   France,   Germany,   Greece,   Hong Kong,   Hungary,   Iceland,   India,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Latvia,   Lithuania,   Malaysia,   Mexico,   Netherlands,   New Zealand,   Norway,   Philippines,   Poland,   Portugal,   Romania,   Russian Federation,   Singapore,   Slovakia,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01764633
Other Study ID Numbers  ICMJE 20110118
2014/01/004324 ( Registry Identifier: Clinical Trials Registry- India (CTRI) )
2012-001398-97 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Amgen
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Amgen
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date March 2023

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