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Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease, The VERTIS CV Study (MK-8835-004)
Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease, The VERTIS CV Study (MK-8835-004)

NCT01986881

CompletedPhase 3

Sponsor: Merck Sharp & Dohme LLC

Conditions: Type 2 Diabetes Mellitus

Interventions: Ertugliflozin, Placebo, Glycemic Rescue

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 overview

Sex: ALL

Age: 40 Years to

Healthy volunteers: No

Study type: INTERVENTIONAL

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.