Sitagliptin Cardiovascular Outcomes Study (MK-0431-082) (TECOS)

This study has been completed.
Sponsor:
Collaborator:
Duke Clinical Research Institute, Oxford Diabetes Trials Unit
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00790205
First received: November 11, 2008
Last updated: May 20, 2016
Last verified: May 2016
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Sitagliptin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants With First Confirmed Cardiovascular (CV) Event of Major Adverse Cardiovascular Event (MACE) Plus (Per Protocol Population) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.

  • Percentage of Participants With First Confirmed CV Event of Major Adverse Cardiovascular Event (MACE) Plus (Intent to Treat Population) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.


Secondary Outcome Measures:
  • Percentage of Participants With First Confirmed CV Event of MACE (Per Protocol Population) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke.

  • Percentage of Participants With First Confirmed CV Event of MACE (Intent to Treat Population) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke.

  • Percent Incidence of All-cause Mortality (Per Protocol Population) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause.

  • Percent Incidence of All-cause Mortality (Intent to Treat Population) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause.

  • Percent Incidence of Congestive Heart Failure (CHF) Requiring Hospitalization (Per Protocol Population) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF.

  • Percent Incidence of CHF Requiring Hospitalization (Intent to Treat Population) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF.

  • Change From Baseline in Renal Function Over Time (Per Protocol Population) [ Time Frame: Baseline and up to 5 years ] [ Designated as safety issue: No ]
    Change in renal function based on estimated glomerular filtration rate [eGFR] using the Modification of Diet in Renal Disease [MDRD] method.

  • Change From Baseline in Renal Function Over Time (Intent to Treat Population) [ Time Frame: Baseline and up to 5 years ] [ Designated as safety issue: No ]
    Change in renal function based on eGFR using the MDRD method.

  • Change From Baseline in HbA1c Over Time (Per Protocol Population) [ Time Frame: Baseline and up to 4 years ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in HbA1c Over Time (Intent to Treat Population) [ Time Frame: Baseline and up to 4 years ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population) [ Time Frame: Baseline and up to 5 years ] [ Designated as safety issue: No ]
    Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value.

  • Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population) [ Time Frame: Baseline and up to 5 years ] [ Designated as safety issue: No ]
    Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value.

  • Percentage of Participants Who Initiated Chronic Insulin Therapy (Per Protocol Population) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.

  • Percentage of Participants Who Initiated Chronic Insulin Therapy (Intent to Treat Population) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.

  • Percentage of Participants With Initiation of Co-interventional Agent (Per Protocol Population) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.)

  • Percentage of Participants With Initiation of Co-interventional Agent (Intent to Treat Population) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.)


Enrollment: 14671
Study Start Date: December 2008
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin
Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years.
Drug: Sitagliptin
Sitagliptin, one 50 mg or one 100 mg tablet (dose dependant on renal function) orally, once daily.
Other Names:
  • MK-0431
  • Januvia®
Placebo Comparator: Placebo
Placebo to sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years.
Drug: Placebo
Placebo tablet matching the 50 mg or 100 mg sitagliptin tablet, orally, once daily.

  Eligibility

Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00790205

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Duke Clinical Research Institute, Oxford Diabetes Trials Unit
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00790205     History of Changes
Other Study ID Numbers: 0431-082  2008_523  2008-006719-20 
Study First Received: November 11, 2008
Results First Received: March 15, 2016
Last Updated: May 20, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 21, 2016