A Study of Tirzepatide (LY3298176) Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes (SURPASS-CVOT)

• ClinicalTrials.gov Identifier: NCT04255433
• Recruitment Status: Active, not recruiting
• First Posted: February 5, 2020
• Last Update Posted: April 26, 2024
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: February 3, 2020
• First Posted Date: February 5, 2020
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: May 29, 2020
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 3, 2020)

Time to First Occurrence of Death from Cardiovascular (CV) Causes, Myocardial Infarction (MI), or Stroke (MACE-3) [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]

Time to First Occurrence of a component event of MACE-3

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 3, 2020)

• Time to Death from Any Cause [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to Death from Any Cause
• Time to CV Death [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to CV Death
• Time to First Occurrence of MI [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to First Occurrence of MI
• Time to First Occurrence of Stroke [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to First Occurrence of Stroke
• Time to First Occurrence of the Expanded Composite of CV Death, MI, Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to First Occurrence of the Expanded Composite of CV Death, MI, Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina
• Cumulative Number of CV Deaths and Total (First and Recurrent) Heart Failure Events Requiring Hospitalization and/or Urgent Heart Failure Visits [ Time Frame: End of Study (Approximate Maximum 54 Months) ]
  Cumulative Number of CV Deaths and Total (First and Recurrent) Heart Failure Events Requiring Hospitalization and/or Urgent Heart Failure Visits
• Percentage of Participants with More than 10% Weight Loss [ Time Frame: 36 Months ]
  Percentage of Participants with More than 10% Weight Loss
• Change from Baseline in Body Weight [ Time Frame: Baseline, End of Study (Approximate Maximum 54 Months) ]
  Change from Baseline in Body Weight
• Change from Baseline in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, End of Study (Approximate Maximum 54 Months) ]
  Change from Baseline in HbA1c
• Change from Baseline in Urinary Albumin to Creatinine Ratio [ Time Frame: Baseline, End of Study (Approximate Maximum 54 Months) ]
  Change from Baseline in Urinary Albumin to Creatinine Ratio
• Change from Baseline in Blood Lipids [ Time Frame: Baseline, End of Study (Approximate Maximum 54 Months) ]
  Change from Baseline in Blood Lipids (Total Cholesterol, Low-Density Lipoprotein Cholesterol, High-Density Lipoprotein Cholesterol, and Triglycerides)
• Time to First Occurrence of Revascularization [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to First Occurrence of Revascularization
• Time to First Occurrence of Hospitalization Due to Unstable Angina [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to First Occurrence of Hospitalization Due to Unstable Angina
• Time to First Occurrence of New or Worsening Nephropathy [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to First Occurrence of New or Worsening Nephropathy
• Cumulative Number of Primary Composite Events of CV Death and Total (First and Recurrent) MI and/or Stroke [ Time Frame: End of Study (Approximate Maximum 54 Months) ]
  Cumulative Number of Primary Composite Events of CV Death and Total (First and Recurrent) MI and/or Stroke

Original Secondary Outcome Measures (submitted: February 3, 2020)

• Time to Death from Any Cause [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to Death from Any Cause
• Time to CV Death [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to CV Death
• Time to First Occurrence of MI [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to First Occurrence of MI
• Time to First Occurrence of Stroke [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to First Occurrence of Stroke
• Percentage of Participants with More than 10% Weight Loss [ Time Frame: 36 Months ]
  Percentage of Participants with More than 10% Weight Loss
• Change from Baseline in Body Weight [ Time Frame: Baseline, End of Study (Approximate Maximum 54 Months) ]
  Change from Baseline in Body Weight
• Change from Baseline in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, End of Study (Approximate Maximum 54 Months) ]
  Change from Baseline in HbA1c
• Change from Baseline in Urinary Albumin to Creatinine Ratio [ Time Frame: Baseline, End of Study (Approximate Maximum 54 Months) ]
  Change from Baseline in Urinary Albumin to Creatinine Ratio
• Change from Baseline in Blood Lipids [ Time Frame: Baseline, End of Study (Approximate Maximum 54 Months) ]
  Change from Baseline in Blood Lipids (Total Cholesterol, Low-Density Lipoprotein Cholesterol, High-Density Lipoprotein Cholesterol, and Triglycerides)
• Time to First Occurrence of Revascularization [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to First Occurrence of Revascularization
• Time to First Occurrence of Hospitalization Due to Unstable Angina [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to First Occurrence of Hospitalization Due to Unstable Angina
• Time to First Occurrence of New or Worsening Nephropathy [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to First Occurrence of New or Worsening Nephropathy
• Time to CV Death, MI, Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina [ Time Frame: Randomization up to Study Completion (Approximate Maximum 54 Months) ]
  Time to CV Death, MI, Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina
• Cumulative Number of Primary Composite Events of CV Death and Total (First and Recurrent) MI and/or Stroke [ Time Frame: End of Study (Approximate Maximum 54 Months) ]
  Cumulative Number of Primary Composite Events of CV Death and Total (First and Recurrent) MI and/or Stroke
• Cumulative Number of CV Deaths and Total (First and Recurrent) Heart Failure Events Requiring Hospitalization and/or Urgent Heart Failure Visits [ Time Frame: End of Study (Approximate Maximum 54 Months) ]
  Cumulative Number of CV Deaths and Total (First and Recurrent) Heart Failure Events Requiring Hospitalization and/or Urgent Heart Failure Visits

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

Descriptive Information

• Brief Title: A Study of Tirzepatide (LY3298176) Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes
• Official Title: The Effect of Tirzepatide Versus Dulaglutide on Major Adverse Cardiovascular Events in Patients With Type 2 Diabetes (SURPASS-CVOT)
• Brief Summary: The purpose of the trial is to assess the efficacy and safety of tirzepatide to dulaglutide in participants with type 2 diabetes and increased cardiovascular risk.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Type 2 Diabetes Mellitus

Intervention

• Drug: Tirzepatide
  Administered SC
  Other Name: LY3298176
• Drug: Dulaglutide
  Administered SC
  Other Name: LY2189265

Study Arms

• Experimental: Tirzepatide
  Tirzepatide administered subcutaneously (SC) once a week.
  Intervention: Drug: Tirzepatide
• Active Comparator: Dulaglutide
  Dulaglutide administered SC once a week.
  Intervention: Drug: Dulaglutide

• Publications *: Kaneko S. Tirzepatide: A Novel, Once-weekly Dual GIP and GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes. touchREV Endocrinol. 2022 Jun;18(1):10-19. doi: 10.17925/EE.2022.18.1.10. Epub 2022 Jun 16.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 3, 2022): 13299
• Original Estimated Enrollment (submitted: February 3, 2020): 12500
• Estimated Study Completion Date: June 2025
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have a diagnosis of type 2 diabetes
• Have confirmed atherosclerotic cardiovascular disease
• HbA1c ≥7.0% to ≤10.5%
• Body mass index (BMI) ≥25 kilograms per meter squared (kg/m²)

Exclusion Criteria:

• Have had a major cardiovascular event within the last 60 days
• Have type 1 diabetes mellitus
• Have a history of severe hypoglycemia and/or hypoglycemia unawareness within the last 6 months
• Are currently planning treatment for diabetic retinopathy and/or macular edema
• Currently planning a coronary, carotid, or peripheral artery revascularization
• Have a history of pancreatitis
• Have a history of ketoacidosis or hyperosmolar state/coma
• Have a known clinically significant gastric emptying abnormality, have undergone or currently planning any gastric outlet obstruction, or have undergone or currently planning any gastric bypass (bariatric) surgery or restrictive bariatric surgery
• Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years
• Have a family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
• Have had a blood transfusion or severe blood loss within 90 days prior to screening or have known hematological conditions that may interfere with HbA1c measurement

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 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, Canada, China, Czechia, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Puerto Rico, Romania, Russian Federation, Slovakia, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04255433
• Other Study ID Numbers: 17073; I8F-MC-GPGN ( Other Identifier: Eli Lilly and Company ); 2019-002735-28 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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: http://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: Not Provided

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: April 2024