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

Primary Purpose

Dyslipidemia

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Evolocumab

Placebo

About this trial

This is an interventional treatment trial for Dyslipidemia focused on measuring High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia

Eligibility Criteria

40 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Evolocumab

Arm Description

Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference.

Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference.

Outcomes

Primary Outcome Measures

Time to Cardiovascular Death, Myocardial Infarction, Hospitalization for Unstable Angina, Stroke, or Coronary Revascularization

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

Time to Cardiovascular Death, Myocardial Infarction, or Stroke

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

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 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

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

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 to Cardiovascular Death or First Hospitalization for Worsening Heart Failure

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: Admitted to hospital with a primary diagnosis of HF In hospital for at least 24 hours 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 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 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

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.

Full Information

NCT ID

NCT01764633

First Posted

January 8, 2013

Last Updated

March 6, 2023

Sponsor

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT01764633

Brief Title

Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk

Acronym

FOURIER

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

February 8, 2013 (Actual)

Primary Completion Date

November 11, 2016 (Actual)

Study Completion Date

November 11, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Dyslipidemia

Keywords

High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

27564 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference.

Arm Title

Evolocumab

Arm Type

Experimental

Arm Description

Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference.

Intervention Type

Biological

Intervention Name(s)

Evolocumab

Other Intervention Name(s)

AMG 145, Repatha

Intervention Description

Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.

Primary Outcome Measure Information:

Title

Time to Cardiovascular Death, Myocardial Infarction, Hospitalization for Unstable Angina, Stroke, or Coronary Revascularization

Description

Time Frame