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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

Tracking Information
First Submitted Date  ICMJE September 7, 2017
First Posted Date  ICMJE September 19, 2017
Last Update Posted Date August 14, 2019
Actual Study Start Date  ICMJE January 23, 2018
Actual Primary Completion Date May 20, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2017)
Percent change in calculated LDL-C in the intent to treat (ITT) population [ Time Frame: Baseline to week 8 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03287609 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2017)
Number of patients with adverse events and serious adverse events [ Time Frame: Baseline to week 8 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 14, 2017)
  • Nominal change in calculated LDL-C [ Time Frame: Baseline to week 8 ]
  • Proportion of patients with LDL-C level <70 mg/dL (<1.8 mmol/L) at week 8 [ Time Frame: Baseline to week 8 ]
  • Change in total cholesterol in the ITT population [ Time Frame: Baseline to week 8 ]
  • Change in HDL-C in the ITT population [ Time Frame: Baseline to week 8 ]
  • Change in lipoprotein-a in the ITT population [ Time Frame: Baseline to week 8 ]
  • Change in triglycerides in the ITT population [ Time Frame: Baseline to week 8 ]
  • Change in non-HDL-C in the ITT population [ Time Frame: Baseline to week 8 ]
  • Change in apolipoprotein B in the ITT population [ Time Frame: Baseline to week 8 ]
  • Change in apolipoprotein A-1 in the ITT population [ Time Frame: Baseline to week 8 ]
  • Percent change in high-sensitivity CRP (hs-CRP) in the ITT population [ Time Frame: Baseline to week 8 ]
  • Proportion of patients with hs-CRP level <2 mg/dL at week 8 in the ITT population [ Time Frame: Baseline to week 8 ]
  • 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 ]
  • Nominal change in Interleukin (IL)-1b and IL-6 in the ITT population [ Time Frame: Baseline to week 8 ]
  • Change in high-sensitivity Troponin T [ Time Frame: Baseline to 72 hours ]
  • 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
  • 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
  • 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 ]
  • 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 ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS)
Official Title  ICMJE EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS) - A Randomized, Double-blind, Placebo-controlled Multicenter Study
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).
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 Acute Coronary Syndrome
Intervention  ICMJE
  • Drug: Evolocumab 140 mg/mL
    Three injections with pre-filled auto-injector pen at day 1 and at week 4.
  • Drug: Placebo
    Three injections with pre-filled auto-injector pen at day 1 and at week 4.
Study Arms  ICMJE
  • Active Comparator: Evolocumab
    Evolocumab 140 mg/mL, pre-filled auto-injector pen, 3 injections at day 1 and week 4
    Intervention: Drug: Evolocumab 140 mg/mL
  • Placebo Comparator: Placebo
    Placebo, pre-filled auto-injector pen, 3 injections at day 1 and week 4
    Intervention: Drug: Placebo
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: September 14, 2017)
308
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 7, 2019
Actual Primary Completion Date May 20, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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 Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03287609
Other Study ID Numbers  ICMJE 2017-01753
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: No plan to make individual participant data available to other researchers
Responsible Party University Hospital Inselspital, Berne
Study Sponsor  ICMJE University Hospital Inselspital, Berne
Collaborators  ICMJE
  • Amgen
  • University of Bern
Investigators  ICMJE
Study Chair: Stephan Windecker, Prof., MD Bern University Hospital
Principal Investigator: Konstantinos Koskinas, MD Bern University Hospital
PRS Account University Hospital Inselspital, Berne
Verification Date August 2019

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