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

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ClinicalTrials.gov Identifier: NCT01764633
Recruitment Status : Completed
First Posted : January 9, 2013
Results First Posted : February 15, 2018
Last Update Posted : February 15, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

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.

Condition or disease Intervention/treatment Phase
Dyslipidemia Biological: Evolocumab Drug: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27564 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 8, 2013
Actual Primary Completion Date : November 11, 2016
Actual Study Completion Date : November 11, 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Evolocumab
U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: Placebo
Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference.
Drug: Placebo
Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.
Experimental: Evolocumab
Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference.
Biological: Evolocumab
Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.
Other Names:
  • AMG 145
  • Repatha



Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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.

  2. 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.


  3. 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.

  4. 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.


  5. 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.


  6. 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.


  7. 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.

  8. 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.




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Ages Eligible for Study:   40 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01764633


  Show 1287 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01764633     History of Changes
Other Study ID Numbers: 20110118
2014/01/004324 ( Registry Identifier: Clinical Trials Registry- India (CTRI) )
2012-001398-97 ( EudraCT Number )
First Posted: January 9, 2013    Key Record Dates
Results First Posted: February 15, 2018
Last Update Posted: February 15, 2018
Last Verified: January 2018

Keywords provided by Amgen:
High cholesterol
Treatment for high cholesterol
Lowering cholesterol
Lowering high cholesterol
Hypercholesterolemia

Additional relevant MeSH terms:
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs