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EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS) (EVOPACS)

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ClinicalTrials.gov Identifier: NCT03287609
Recruitment Status : Completed
First Posted : September 19, 2017
Last Update Posted : August 14, 2019
Sponsor:
Collaborators:
Amgen
University of Bern
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Brief Summary:
Reduction of low-density lipoprotein cholesterol (LDL-C) levels effectively reduces the risk of adverse events in patients with established atherosclerotic cardiovascular disease. The clinical benefit of statins in improving clinical outcomes is proportional to the magnitude of LDL-C reduction, is more pronounced in patients with acute coronary syndromes (ACS) compared with stable coronary artery disease, and emerges at very early stages (as early as 4 weeks) after ACS when statins are administered in the acute phase of the event. On the basis of this evidence, early initiation of statin therapy is currently recommended in patients presenting with ACS. Because many patients cannot achieve adequate reduction of LDL-C levels despite treatment with high doses of statins or non-statin lipid-modifying medications, substantial residual risk remains. Moreover, the time of onset of LDL-C reduction takes 2 weeks following initiation of statin therapy. Proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors represent a novel class of lipid-lowering drugs leading to rapid, profound, and consistent reductions in LDL-C levels. While the effectiveness of PCSK9 monoclonal antibodies for LDL-C lowering has been established across patient populations without atherosclerotic cardiovascular disease or with stable ischemic heart disease, reduction and attainment of LDL-C target levels has not been explored in the acute setting of ACS - a clinical setting with highest risk of early event recurrence (within the first month). In this study the investigators want to evaluate the safety and effectiveness of the PCSK9 inhibitor evolocumab as compared with placebo, administered in the acute phase of ACS, for reduction of LDL-C levels within 8 weeks in patients receiving guideline-recommended high-intensity statin treatment (atorvastatin 40mg QD).

Condition or disease Intervention/treatment Phase
Acute Coronary Syndrome Drug: Evolocumab 140 mg/mL Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 308 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS) - A Randomized, Double-blind, Placebo-controlled Multicenter Study
Actual Study Start Date : January 23, 2018
Actual Primary Completion Date : May 20, 2019
Actual Study Completion Date : August 7, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Evolocumab

Arm Intervention/treatment
Active Comparator: Evolocumab
Evolocumab 140 mg/mL, pre-filled auto-injector pen, 3 injections at day 1 and week 4
Drug: Evolocumab 140 mg/mL
Three injections with pre-filled auto-injector pen at day 1 and at week 4.

Placebo Comparator: Placebo
Placebo, pre-filled auto-injector pen, 3 injections at day 1 and week 4
Drug: Placebo
Three injections with pre-filled auto-injector pen at day 1 and at week 4.




Primary Outcome Measures :
  1. Percent change in calculated LDL-C in the intent to treat (ITT) population [ Time Frame: Baseline to week 8 ]

Secondary Outcome Measures :
  1. Number of patients with adverse events and serious adverse events [ Time Frame: Baseline to week 8 ]

Other Outcome Measures:
  1. Nominal change in calculated LDL-C [ Time Frame: Baseline to week 8 ]
  2. Proportion of patients with LDL-C level <70 mg/dL (<1.8 mmol/L) at week 8 [ Time Frame: Baseline to week 8 ]
  3. Change in total cholesterol in the ITT population [ Time Frame: Baseline to week 8 ]
  4. Change in HDL-C in the ITT population [ Time Frame: Baseline to week 8 ]
  5. Change in lipoprotein-a in the ITT population [ Time Frame: Baseline to week 8 ]
  6. Change in triglycerides in the ITT population [ Time Frame: Baseline to week 8 ]
  7. Change in non-HDL-C in the ITT population [ Time Frame: Baseline to week 8 ]
  8. Change in apolipoprotein B in the ITT population [ Time Frame: Baseline to week 8 ]
  9. Change in apolipoprotein A-1 in the ITT population [ Time Frame: Baseline to week 8 ]
  10. Percent change in high-sensitivity CRP (hs-CRP) in the ITT population [ Time Frame: Baseline to week 8 ]
  11. Proportion of patients with hs-CRP level <2 mg/dL at week 8 in the ITT population [ Time Frame: Baseline to week 8 ]
  12. Proportion of patients with LDL-C <70 mg/dL and hs-CRP <2 mg/dL at week 8 in the ITT population [ Time Frame: Baseline to week 8 ]
  13. Nominal change in Interleukin (IL)-1b and IL-6 in the ITT population [ Time Frame: Baseline to week 8 ]
  14. Change in high-sensitivity Troponin T [ Time Frame: Baseline to 72 hours ]
  15. Area under the curve (AUC) at Multiplate with Adenosinediphosphate (ADP) test [ Time Frame: Baseline to 72 hours and to week 8 ]
    Platelet inhibition assessed with Multiplate ADP test at 72 hours and 8 weeks

  16. Area under the curve (AUC) at Multiplate with Thrombin receptor activating peptide (TRAP) test [ Time Frame: Baseline to 72 hours and to week 8 ]
    Platelet inhibition assessed with Multiplate TRAP test at 72 hours and 8 weeks

  17. Number of patients with contrast-induced acute kidney injury (CI-AKI) at 72 hours among patients who undergo coronary angiography at baseline [ Time Frame: Baseline to 72 hours ]
  18. Number of patients with adjudicated events (death, cardiovascular death, myocardial infarction, hospitalization for recurrent ACS, hospitalization for heart failure, coronary revascularization, stroke [ Time Frame: Baseline to week 8 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Male or female ≥ 18 years of age;

  • Hospitalized for a recent ACS;
  • LDL-C levels defined as follows:
  • LDL-C ≥70 mg/dL (≥1.8 mmol/L) or non-HDL-C ≥100 mg/dL (≥2.6 mmol/) in patients who have been receiving stable treatment with high-intensity statin within ≥ 4 weeks prior to enrollment (i.e. continuous treatment that has not changed with regard to statin intensity over the past 4 weeks) or, LDL-C ≥90 mg/dL (≥2.3 mmol/L) or non-HDL-C ≥120 mg/dL (≥3.1 mmol/) in patients who have been receiving stable treatment with low- or moderate-intensity statin within ≥ 4 weeks prior to enrollment (i.e. continuous treatment that has not changed with regard to statin intensity over the past 4 weeks), or LDL-C ≥125 mg/dL (≥3.2 mmol/L) or non-HDL-C ≥155 mg/dL (≥4.0 mmol/) in patients who are statin-naïve or have not been on a stable (unchanged) statin regimen for at least 4 weeks prior to enrollment;
  • Ability to understand the requirements of the study and to provide informed consent.

Exclusion Criteria:

  • Unstable clinical status (hemodynamic or electrical instability;
  • Uncontrolled cardiac arrhythmia, defined as recurrent and symptomatic ventricular tachycardia or atrial fibrillation with rapid ventricular response not controlled by medications in the past 3 months prior to screening;
  • Severe renal dysfunction, defined by estimated glomerular filtration rate <30 ml/min/1.73m2;
  • Active liver disease or hepatic dysfunction, either reported in patient medical record or defined by asparate aminotransferase (AST) or alanine aminotransferase (ALT) levels > 3x the upper limit of normal;
  • Reported intolerance to atorvastatin (any dose) OR statin intolerance;
  • Known allergy to contrast medium, heparin, aspirin, ticagrelor or prasugrel;
  • Known sensitivity to any substances to be administered;
  • Patients who previously received evolocumab or other PCSK9 inhibitor;
  • Patient who received cholesterol ester transfer protein inhibitors in the past 12 months prior to screening;
  • Treatment with systemic steroids or systemic cyclosporine in the past 3 months systemic cyclosporine, systemic steroids (eg. intravenous, intramuscular or per os);
  • Known active infection or major hematologic, metabolic, or endocrine dysfunction in the judgment of the Investigator;
  • Patients who will not be available for study-required procedures in the judgment of the Investigator;
  • Current enrollment in another investigational device or drug study;
  • Active malignancy requiring treatment;
  • Female of childbearing potential (age <50 years and last menstruation within the last 12 months), who did not undergo tubal ligation, ovariectomy or hysterectomy.

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): NCT03287609


Locations
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Switzerland
Basel University Hospital
Basel, BS, Switzerland, 4031
HFR Kantonsspital
Fribourg, FR, Switzerland, 1708
Hopitaux Universitaires Geneve
Geneva, GE, Switzerland, 1211
Cardiocentro Ticino
Lugano, TI, Switzerland, 6900
Centre Hospitalier Universitaire Vaudois
Lausanne, VD, Switzerland
University Hospital
Zurich, ZH, Switzerland
Bern University Hospital
Bern, Switzerland, 3010
Sponsors and Collaborators
University Hospital Inselspital, Berne
Amgen
University of Bern
Investigators
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Study Chair: Stephan Windecker, Prof., MD Bern University Hospital
Principal Investigator: Konstantinos Koskinas, MD Bern University Hospital

Publications of Results:

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Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT03287609     History of Changes
Other Study ID Numbers: 2017-01753
First Posted: September 19, 2017    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan to make individual participant data available to other researchers

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Acute Coronary Syndrome
Syndrome
Disease
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Evolocumab
Antibodies, Monoclonal
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Immunologic Factors
Physiological Effects of Drugs