A Study of Evacetrapib in High-Risk Vascular Disease (ACCELERATE)

• ClinicalTrials.gov Identifier: NCT01687998
• Recruitment Status: Terminated
• First Posted: September 19, 2012
• Results First Posted: May 16, 2018
• Last Update Posted: October 8, 2019
• Sponsor: Eli Lilly and Company
• Collaborator: The Cleveland Clinic
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: September 12, 2012
• First Posted Date: September 19, 2012
• Results First Submitted Date: February 18, 2018
• Results First Posted Date: May 16, 2018
• Last Update Posted Date: October 8, 2019
• Study Start Date: October 2012
• Actual Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 13, 2018)

Number of Participants With Composite Primary Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina (UA) [ Time Frame: Baseline to Study Completion (Up to 4 years) ]

For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously.

• Original Primary Outcome Measures (submitted: September 14, 2012): Time to First Occurence of the Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina (UA) [ Time Frame: Baseline to Study Completion (estimated to be up to 4 years) ]

Current Secondary Outcome Measures (submitted: April 13, 2018)

• Mean Percent Change From Baseline to 3 Months in Low-Density (LDL-C) and High-Density Lipoprotein Cholesterol (HDL-C) Levels [ Time Frame: Baseline, 3 Months ]
• Number of Participants With Composite Endpoint of All-Cause Mortality, MI, Stroke, Coronary Revascularization, or Hospitalization for UA [ Time Frame: Baseline through End of Study (Up to 4 years) ]
  For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously.
• Number of Participants With Composite Endpoint of CV Death, MI, or Coronary Revascularization [ Time Frame: Baseline through End of Study (Up to 4 years) ]
  For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously.
• Number of Participants With Composite Endpoint of CV Death, MI, Stroke, or Hospitalization for UA [ Time Frame: Baseline through End of Study (Up to 4 years) ]
  For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously.
• Number of Participants With Triple Composite Endpoint of CV Death, MI, or Stroke [ Time Frame: Baseline through End of Study (Up to 4 years) ]
  For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously.

Original Secondary Outcome Measures (submitted: September 14, 2012)

• Mean Percent Change from Baseline to 3 Months in Low-Density (LDL-C) and High-Density Lipoprotein Cholesterol (HDL-C) levels [ Time Frame: Baseline, 3 Months ]
• Time to First Occurrence of the Composite Endpoint of All-Cause Mortality, MI, Stroke, Coronary Revascularization, or Hospitalization for UA [ Time Frame: Baseline through End of Study (estimated up to 4 years) ]
• Time to First Occurrence of the Composite Endpoint of CV Death, MI, or Coronary Revascularization [ Time Frame: Baseline through End of Study (estimated up to 4 years) ]
• Time to First Occurrence of the Composite Endpoint of CV Death, MI, Stroke, or Hospitalization for UA [ Time Frame: Baseline through End of Study (estimated up to 4 years) ]
• Time to First Occurrence of Composite Endpoint of CV Death, MI, or Stroke [ Time Frame: Baseline through End of Study (estimated up to 4 years) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Evacetrapib in High-Risk Vascular Disease
• Official Title: Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High-Risk for Vascular Outcomes
• Brief Summary: The purpose of the ACCELERATE study is to evaluate the efficacy and safety of evacetrapib in participants with high-risk vascular disease (HRVD).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cardiovascular Diseases

Intervention

• Drug: Evacetrapib
  Administered Orally
  Other Name: LY2484595
• Drug: Placebo
  Administered Orally

Study Arms

• Experimental: Evacetrapib
  Evacetrapib 130 mg tablet, administered orally once daily for up to 4 years. Participants will also receive standard of care for high-risk vascular disease (HRVD).
  Intervention: Drug: Evacetrapib
• Placebo Comparator: Placebo
  Placebo, tablet administered orally once daily for up to 4 years. Participants will also receive standard of care for HRVD.
  Intervention: Drug: Placebo

Publications *

• Puri R, Nissen SE, Arsenault BJ, St John J, Riesmeyer JS, Ruotolo G, McErlean E, Menon V, Cho L, Wolski K, Lincoff AM, Nicholls SJ. Effect of C-Reactive Protein on Lipoprotein(a)-Associated Cardiovascular Risk in Optimally Treated Patients With High-Risk Vascular Disease: A Prespecified Secondary Analysis of the ACCELERATE Trial. JAMA Cardiol. 2020 Oct 1;5(10):1136-1143. doi: 10.1001/jamacardio.2020.2413.
• Menon V, Kumar A, Patel DR, John JS, Wolski KE, McErlean E, Riesmeyer JS, Weerakkody G, Ruotolo G, Cremer PC, Nicholls SJ, Lincoff AM, Nissen SE. Impact of Baseline Glycemic Control on Residual Cardiovascular Risk in Patients With Diabetes Mellitus and High-Risk Vascular Disease Treated With Statin Therapy. J Am Heart Assoc. 2020 Jan 7;9(1):e014328. doi: 10.1161/JAHA.119.014328. Epub 2019 Dec 19.
• Kumar A, Patel DR, Brennan DM, Wolski KE, Lincoff AM, Ruotolo G, McErlean E, Weerakkody G, Riesmeyer JS, Nicholls SJ, Nissen SE, Menon V. Plasma Aldosterone Levels Are Not Associated With Cardiovascular Events Among Patients With High-Risk Vascular Disease: Insights From the ACCELERATE Trial. J Am Heart Assoc. 2019 Dec 3;8(23):e013790. doi: 10.1161/JAHA.119.013790. Epub 2019 Nov 22.
• Lincoff AM, Nicholls SJ, Riesmeyer JS, Barter PJ, Brewer HB, Fox KAA, Gibson CM, Granger C, Menon V, Montalescot G, Rader D, Tall AR, McErlean E, Wolski K, Ruotolo G, Vangerow B, Weerakkody G, Goodman SG, Conde D, McGuire DK, Nicolau JC, Leiva-Pons JL, Pesant Y, Li W, Kandath D, Kouz S, Tahirkheli N, Mason D, Nissen SE; ACCELERATE Investigators. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease. N Engl J Med. 2017 May 18;376(20):1933-1942. doi: 10.1056/NEJMoa1609581.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 12, 2016): 12092
• Original Estimated Enrollment (submitted: September 14, 2012): 11000
• Actual Study Completion Date: July 2016
• Actual Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of high risk vascular disease (HRVD) (that is, meet at least one of the disease diagnostic criteria of: 1)History of acute coronary syndrome (ACS) (that is, ≥30 days through 365 days after discharge for ACS) 2)cerebrovascular atherosclerotic disease 3)peripheral arterial disease 4)diabetes mellitus with documented coronary artery disease and are clinically stable (as judged by the responsible physician).
• Must be treated with a statin for at least 30 days prior to screening. If not treated with a statin must have documented statin intolerance, or contraindication to statin
• Have a screening high-density lipoprotein cholesterol (HDL-C) ≤80 milligram per deciliter (mg/dL) (≤2.1 millimole per liter [mmol/L])
• Have screening triglycerides (TG) ≤400 mg/dL (≤4.5 mmol/L)

• Meet 1 of the following criteria:

  • screening low-density lipoprotein cholesterol (LDL-C) no more than 10 mg/dL (0.3 mmol/L) above the target chosen by the investigator (either LDL-C <100 mg/dL [<2.6 mmol/L] or LDL-C <70 mg/dL [<1.8 mmol/L]), OR
  • if LDL-C is greater than target, the participant must be on maximum tolerated statin dose (for at least 30 days), have documented statin intolerance, or contraindication to statin

Exclusion Criteria:

• Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Have previously completed or withdrawn from this study, or withdrawn from any other study investigating evacetrapib
• Female participants who are known to be pregnant or breastfeeding
• Women of child-bearing potential only, who test positive for pregnancy between screening and randomization, or who do not agree to use a reliable method of birth control during the study
• History of transient ischemic attack (TIA) or ischemic stroke <30 days and ACS <30 days
• Any reading of systolic blood pressure ≥180 millimeter of mercury (mm Hg) or diastolic blood pressure ≥110 mm Hg at screening or randomization
• History of hemorrhagic stroke or intracranial hemorrhage
• New York Heart Association class III or IV congestive heart failure
• Serum creatinine >2.2 mg/dL (>194.5 micromole per liter [μmol/L]) at screening
• Clinically active liver disease. Participants are not excluded due to Gilbert's Syndrome or a history of cholelithiasis/cholecystectomy
• History of malignancy within the preceding 3 years prior to screening
• Known malabsorption syndrome with the exception of lactose intolerance
• Participants with a known history of primary or secondary hyperaldosteronism
• Participants with a history of intolerance/hypersensitivity to cholesterol ester transfer protein (CETP) inhibitors
• Any clinically significant medical condition that according to the investigator could interfere with participation in the study
• Participants whose life expectancy is anticipated to be less than 4 years
• Unable or unwilling to comply with study requirements, or deemed by the investigator to be unfit for the study
• Have a history of drug, alcohol, or substance abuse within the past 6 months, as assessed by the investigator
• Concurrent or anticipated need for treatment with niacin >250 mg/day or for chronic administration of drugs on the exclusion list
• Previous exposure to the CETP inhibitors dalcetrapib or evacetrapib within the last 3 months or anacetrapib within the last 12 months
• Any planned coronary angiography or coronary revascularization procedure. If angiography or revascularization is planned, participants may be screened and enrolled after all such planned procedures are completed.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, Estonia, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Lithuania, Mexico, Netherlands, New Zealand, Poland, Puerto Rico, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Czech Republic, India, Peru

Administrative Information

• NCT Number: NCT01687998
• Other Study ID Numbers: 11949; I1V-MC-EIAN ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: The Cleveland Clinic

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: September 2019