Sitagliptin Cardiovascular Outcomes Study (MK-0431-082)

Merck Sharp & Dohme LLC14,671 enrolled

Overview

This is a clinical trial designed to assess the cardiovascular outcome of long-term treatment with sitagliptin used as part of usual care compared to usual care without sitagliptin in participants with type 2 diabetes mellitus (T2DM) having a history of cardiovascular (CV) disease and a hemoglobin A1c (HbA1c) of 6.5% to 8.0%. Primary hypothesis A is that sitagliptin, when used as part of usual care, is non-inferior to usual care without sitagliptin with regard to the risk of developing a confirmed event in the primary CV composite endpoint of Major Adverse Cardiovascular Event (MACE) plus. If hypothesis A is satisfied: hypothesis B is that sitagliptin, when used as part of usual care, is superior to usual care without sitagliptin with regard to the risk of developing a confirmed event in the primary CV composite endpoint.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

14,671

Conditions

Type 2 Diabetes Mellitus

Interventions

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Has T2DM * Has HbA1c between 6.5% (48 mmol/mol) and 8.0% (64 mmol/mol) on stable dose(s) of antihyperglycemic agent(s), including insulin * Has pre-existing cardiovascular disease Exclusion Criteria: * Has a history of type 1 diabetes mellitus or ketoacidosis. * Is not able to take sitagliptin

Outcomes

Primary Outcomes

Percentage of Participants With First Confirmed Cardiovascular (CV) Event of Major Adverse Cardiovascular Event (MACE) Plus (Per Protocol Population)

Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.

Time frame: Up to 5 years

Percentage of Participants With First Confirmed CV Event of Major Adverse Cardiovascular Event (MACE) Plus (Intent to Treat Population)

Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.

Time frame: Up to 5 years

Secondary Outcomes

Percentage of Participants With First Confirmed CV Event of MACE (Per Protocol Population)

CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke.

Time frame: Up to 5 years

Percentage of Participants With First Confirmed CV Event of MACE (Intent to Treat Population)

CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke.

Time frame: Up to 5 years

Percent Incidence of All-cause Mortality (Per Protocol Population)

Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause.

Time frame: Up to 5 years

Percent Incidence of All-cause Mortality (Intent to Treat Population)

Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause.

Time frame: Up to 5 years

Percent Incidence of Congestive Heart Failure (CHF) Requiring Hospitalization (Per Protocol Population)

Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF.

Time frame: Up to 5 years

Percent Incidence of CHF Requiring Hospitalization (Intent to Treat Population)

Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF.

Time frame: Up to 5 years

Change From Baseline in Renal Function Over Time (Per Protocol Population)

Change in renal function based on estimated glomerular filtration rate \[eGFR\] using the Modification of Diet in Renal Disease \[MDRD\] method.

Time frame: Baseline and up to 5 years

Change From Baseline in Renal Function Over Time (Intent to Treat Population)

Change in renal function based on eGFR using the MDRD method.

Time frame: Baseline and up to 5 years

Change From Baseline in HbA1c Over Time (Per Protocol Population)

HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Estimated mean difference between sitagliptin and placebo controlling for baseline HbA1c and region.

Time frame: Baseline and up to 4 years

Change From Baseline in HbA1c Over Time (Intent to Treat Population)

HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Estimated mean difference between sitagliptin and placebo controlling for baseline HbA1c and region.

Time frame: Baseline and up to 4 years

Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population)

Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value.

Time frame: Baseline and up to 5 years

Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population)

Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value.

Time frame: Baseline and up to 5 years

Percentage of Participants Who Initiated Chronic Insulin Therapy (Per Protocol Population)

Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.

Time frame: Up to 5 years

Percentage of Participants Who Initiated Chronic Insulin Therapy (Intent to Treat Population)

Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.

Time frame: Up to 5 years

Percentage of Participants With Initiation of Co-interventional Agent (Per Protocol Population)

In participants not receiving insulin at baseline, time to addition of first co-interventional agent (i.e., next oral antihyperglycemic agent \[AHA\] or chronic insulin, where chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.)

Time frame: Up to 5 years

Percentage of Participants With Initiation of Co-interventional Agent (Intent to Treat Population)

In participants not receiving insulin at baseline, time to addition of first co-interventional agent (i.e., next oral AHA or chronic insulin, where chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.)

Time frame: Up to 5 years