Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease, The VERTIS CV Study (MK-8835-004)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Vascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Ertugliflozin; Placebo; Glycemic Rescue
Intervention description: Oral, once daily, for up to approximately 6 years; Matching placebo to ertugliflozin administered orally, once daily, for up to approximately 6 years; Doses of background anti-hyperglycemic agents (AHA), medications will be required to be held constant in all participants enrolled for the initial 18 weeks of the trial with 2 exceptions: First, participant will be prescribed glycemic rescue therapy if they meet specific, progressively more stringent, glycemic thresholds based on repeated, confirmed fasting plasma glucose (FPG) measured at a central laboratory. Second, a participant experiencing clinically significant hypoglycemia according to the investigator at any time during the trial is permitted to have the dose of appropriate background AHA (e.g., insulin, sulfonylurea [SU], glinide) reduced or discontinued as per the judgment of the investigator or the treating physician. Choice and dosing of glycemic rescue will be at the discretion of the investigator or the treating physician consistent with standards of care for management of patients with Type 2 diabetes mellitus (T2DM) within the country of the investigational site.
Intervention MeSH terms: Ertugliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 8246.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

Summary:

      An overall study of the cardiovascular outcomes following treatment with ertugliflozin in
      participants with type 2 diabetes mellitus (T2DM) and established vascular disease. The main
      objective of this study is to assess the cardiovascular safety of ertugliflozin. This trial
      includes 3 pre-defined glycemic sub-studies; 1. In participants receiving background insulin
      with or without metformin, 2. In participants receiving background sulfonylurea monotherapy,
      and 3. In participants receiving background metformin with sulfonylurea (all fully-enrolled).

      Participants enrolled prior to Amendment 1 were in the overall study as well as a sub-study,
      if they met certain entry criteria. Participants enrolled following the start of Amendment 1
      were only enrolled in the overall study. The sub-studies were the initial 18 weeks of the
      overall study period.
    

Eligibility criteria:

        Inclusion Criteria (Overall Cardiovascular Study):

          -  Diagnosis of T2DM in accordance with American Diabetes Association (ADA) guidelines

          -  Hemoglobin A1c (A1C) at the start of study participation of 7.0-10.5% (53-91 mmol/mol)

          -  On stable allowable anti-hyperglycemic agents (AHA) or on no background AHA for at
             least 8 weeks prior to the study participation

          -  Body Mass Index (BMI) > or = to 18.0 kg/m^2

          -  Evidence or a history of atherosclerosis involving the coronary, cerebral or
             peripheral vascular systems

          -  There is adequate documentation of the objective evidence that the participant has
             established vascular disease such as investigational site's medical records, copies of
             such records from other institutions, or a letter from a referring physician that
             specifically states the diagnosis and date of the most recent occurrence of the
             qualifying event(s) or procedure(s).

          -  Male, female not or reproductive potential, or female of reproductive potential who
             agrees to be abstinent from heterosexual activity or agrees to use or have their
             partner use 2 acceptable methods of contraception

        Exclusion Criteria (Overall Cardiovascular Study):

          -  Previous randomization into this trial

          -  Experiencing a cardiovascular event (myocardial infarction or stroke) or undergoing
             coronary angioplasty or peripheral intervention procedure between the Screening Visit
             and randomization

          -  Undergoing any cardiovascular surgery (valvular surgery) within 3 months of study
             participation

          -  Planned revascularization or peripheral intervention procedure or other cardiovascular
             surgery

          -  New York Heart Association (NYHA) IV heart failure at study participation

          -  History of type 1 diabetes mellitus or a history of ketoacidosis

        Key Inclusion Criteria for the 3 Glycemic Sub-studies:

          1. Insulin With or Without Metformin Sub-study: Stable doses of insulin (>=20 units/day,
             with variations up to 10% in the daily dose permitted) with or without metformin
             (>=1500 mg/day) for at least 8 weeks prior to the time of the Screening Visit (V1) and
             during the period between the Screening Visit (V1) and randomization.

          2. Sulfonylurea (SU) Monotherapy Sub-study: Participants receiving a stable dose of SU
             monotherapy for at least 8 weeks prior to the time of the Screening Visit (V1) and
             during the period between the Screening Visit (V1) and randomization.

          3. Metformin with SU Sub-study: Participants receiving a stable dose metformin (≥1500
             mg/day) with a SU for at least 8 weeks prior to the time of the Screening Visit (V1)
             and during the period between the Screening Visit (V1) and randomization.