Sitagliptin Cardiovascular Outcomes Study (MK-0431-082)

Study Overview
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Brief Summary
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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.

Official Title
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TECOS: A Randomized, Placebo Controlled Clinical Trial to Evaluate Cardiovascular Outcomes After Treatment With Sitagliptin in Patients With Type 2 Diabetes Mellitus and Inadequate Glycemic Control

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin<br>Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years. | Drug: Sitagliptin<br>* Sitagliptin, one 50 mg or one 100 mg tablet (dose dependant on renal function) orally, once daily.<br>* Other names: Januvia®;|
| Placebo Comparator: Placebo<br>Placebo to sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years. | Drug: Placebo<br>* Placebo tablet matching the 50 mg or 100 mg sitagliptin tablet, orally, once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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.) | 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.) | Up to 5 years |