cardiovascular outcomes following ertugliflozin treatment in type 2 diabetes mellitus participants with vascular disease, the vertis cv study (mk-8835-004)

Conditions: Type 2 Diabetes Mellitus

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.

the primary hypotheses for the 4 studies are: 1. overall cardiovascular study: the time to first occurrence of the composite endpoint of mace: cardiovascular death, non-fatal myocardial infarction \[mi\] or non-fatal stroke in participants treated with ertugliflozin is non-inferior compared to that in participants treated with placebo. 2. the 3 glycemic sub-studies: 1. the mean reduction from baseline in hemoglobin a1c (a1c) for 15 mg ertugliflozin is greater than that for placebo. 2. the mean reduction from baseline in a1c for 5 mg ertugliflozin is greater than that for placebo.

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.