November 11, 2008
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November 13, 2008
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March 15, 2016
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April 15, 2016
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November 23, 2021
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December 10, 2008
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March 30, 2015 (Final data collection date for primary outcome measure)
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- 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 ]
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 ]
Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.
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Assess primary composite cardiovascular endpoint (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or unstable angina requiring hospitalization [ Time Frame: Approximately 4-5 years ]
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- Percentage of Participants With First Confirmed CV Event of MACE (Per Protocol Population) [ Time Frame: Up to 5 years ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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.)
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Assess secondary composite cardiovascular endpoint (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) [ Time Frame: Approximately 4-5 years ]
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Not Provided
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Not Provided
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Sitagliptin Cardiovascular Outcomes Study (MK-0431-082)
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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
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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.
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Not Provided
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Interventional
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Phase 3
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment
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Type 2 Diabetes Mellitus
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- Drug: Sitagliptin
Sitagliptin, one 50 mg or one 100 mg tablet (dose dependant on renal function) orally, once daily.
- Drug: Placebo
Placebo tablet matching the 50 mg or 100 mg sitagliptin tablet, orally, once daily.
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- Experimental: Sitagliptin
Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years.
Intervention: Drug: Sitagliptin
- Placebo Comparator: Placebo
Placebo to sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years.
Intervention: Drug: Placebo
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- Green JB, Bethel MA, Paul SK, Ring A, Kaufman KD, Shapiro DR, Califf RM, Holman RR. Rationale, design, and organization of a randomized, controlled Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) in patients with type 2 diabetes and established cardiovascular disease. Am Heart J. 2013 Dec;166(6):983-989.e7. doi: 10.1016/j.ahj.2013.09.003. Epub 2013 Oct 23.
- Bethel MA, Green JB, Milton J, Tajar A, Engel SS, Califf RM, Holman RR; TECOS Executive Committee. Regional, age and sex differences in baseline characteristics of patients enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Diabetes Obes Metab. 2015 Apr;17(4):395-402. doi: 10.1111/dom.12441. Epub 2015 Feb 13.
- Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR; TECOS Study Group. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2015 Jul 16;373(3):232-42. doi: 10.1056/NEJMoa1501352. Epub 2015 Jun 8. Erratum in: N Engl J Med. 2015 Aug 6;373(6):586.
- Sharma A, Zheng Y, Ezekowitz JA, Westerhout CM, Udell JA, Goodman SG, Armstrong PW, Buse JB, Green JB, Josse RG, Kaufman KD, McGuire DK, Ambrosio G, Chuang LM, Lopes RD, Peterson ED, Holman RR. Cluster Analysis of Cardiovascular Phenotypes in Patients With Type 2 Diabetes and Established Atherosclerotic Cardiovascular Disease: A Potential Approach to Precision Medicine. Diabetes Care. 2022 Jan 1;45(1):204-212. doi: 10.2337/dc20-2806.
- McAlister FA, Zheng Y, Westerhout CM, Buse JB, Standl E, McGuire DK, Van de Werf F, Green JB, Armstrong PW, Holman RR; TECOS Study Group. Association between glycated haemoglobin levels and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the TECOS randomized clinical trial. Eur J Heart Fail. 2020 Nov;22(11):2026-2034. doi: 10.1002/ejhf.1958. Epub 2020 Jul 28.
- De Ferrari GM, Stevens SR, Ambrosio G, Leonardi S, Armstrong PW, Green JB, Wamil M, Holman RR, Peterson ED; TECOS Study Group. Low-density lipoprotein cholesterol treatment and outcomes in patients with type 2 diabetes and established cardiovascular disease: Insights from TECOS. Am Heart J. 2020 Feb;220:82-88. doi: 10.1016/j.ahj.2019.11.005. Epub 2019 Nov 13.
- Shavadia JS, Zheng Y, Green JB, Armstrong PW, Westerhout CM, McGuire DK, Cornel JH, Holman RR, Peterson ED. Associations between β-blocker therapy and cardiovascular outcomes in patients with diabetes and established cardiovascular disease. Am Heart J. 2019 Dec;218:92-99. doi: 10.1016/j.ahj.2019.09.013. Epub 2019 Oct 20.
- Nauck MA, McGuire DK, Pieper KS, Lokhnygina Y, Strandberg TE, Riefflin A, Delibasi T, Peterson ED, White HD, Scott R, Holman RR. Sitagliptin does not reduce the risk of cardiovascular death or hospitalization for heart failure following myocardial infarction in patients with diabetes: observations from TECOS. Cardiovasc Diabetol. 2019 Sep 3;18(1):116. doi: 10.1186/s12933-019-0921-2.
- Guimarães PO, Peterson ED, Stevens SR, Lokhnygina Y, Green JB, McGuire DK, Holman RR, Lopes RD. Antithrombotic treatment gap among patients with atrial fibrillation and type 2 diabetes. Int J Cardiol. 2019 Aug 15;289:58-62. doi: 10.1016/j.ijcard.2019.04.085. Epub 2019 Apr 30.
- Reed SD, Li Y, Leal J, Radican L, Adler AI, Alfredsson J, Buse JB, Green JB, Kaufman KD, Riefflin A, Van de Werf F, Peterson ED, Gray AM, Holman RR; TECOS Study Group. Longitudinal medical resources and costs among type 2 diabetes patients participating in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Diabetes Obes Metab. 2018 Jul;20(7):1732-1739. doi: 10.1111/dom.13292. Epub 2018 Apr 20.
- Standl E, Stevens SR, Armstrong PW, Buse JB, Chan JCN, Green JB, Lachin JM, Scheen A, Travert F, Van de Werf F, Peterson ED, Holman RR; TECOS Study Group. Increased Risk of Severe Hypoglycemic Events Before and After Cardiovascular Outcomes in TECOS Suggests an At-Risk Type 2 Diabetes Frail Patient Phenotype. Diabetes Care. 2018 Mar;41(3):596-603. doi: 10.2337/dc17-1778. Epub 2018 Jan 8.
- Sharma A, Green JB, Dunning A, Lokhnygina Y, Al-Khatib SM, Lopes RD, Buse JB, Lachin JM, Van de Werf F, Armstrong PW, Kaufman KD, Standl E, Chan JCN, Distiller LA, Scott R, Peterson ED, Holman RR; TECOS Study Group. Causes of Death in a Contemporary Cohort of Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: Insights From the TECOS Trial. Diabetes Care. 2017 Dec;40(12):1763-1770. doi: 10.2337/dc17-1091. Epub 2017 Oct 6.
- Pagidipati NJ, Navar AM, Pieper KS, Green JB, Bethel MA, Armstrong PW, Josse RG, McGuire DK, Lokhnygina Y, Cornel JH, Halvorsen S, Strandberg TE, Delibasi T, Holman RR, Peterson ED; TECOS Study Group. Secondary Prevention of Cardiovascular Disease in Patients With Type 2 Diabetes Mellitus: International Insights From the TECOS Trial (Trial Evaluating Cardiovascular Outcomes With Sitagliptin). Circulation. 2017 Sep 26;136(13):1193-1203. doi: 10.1161/CIRCULATIONAHA.117.027252. Epub 2017 Jun 16.
- Bethel MA, Engel SS, Green JB, Huang Z, Josse RG, Kaufman KD, Standl E, Suryawanshi S, Van de Werf F, McGuire DK, Peterson ED, Holman RR; TECOS Study Group. Assessing the Safety of Sitagliptin in Older Participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Diabetes Care. 2017 Apr;40(4):494-501. doi: 10.2337/dc16-1135. Epub 2017 Jan 5.
- Cornel JH, Bakris GL, Stevens SR, Alvarsson M, Bax WA, Chuang LM, Engel SS, Lopes RD, McGuire DK, Riefflin A, Rodbard HW, Sinay I, Tankova T, Wainstein J, Peterson ED, Holman RR; TECOS Study Group. Effect of Sitagliptin on Kidney Function and Respective Cardiovascular Outcomes in Type 2 Diabetes: Outcomes From TECOS. Diabetes Care. 2016 Dec;39(12):2304-2310. Epub 2016 Oct 14.
- Buse JB, Bethel MA, Green JB, Stevens SR, Lokhnygina Y, Aschner P, Grado CR, Tankova T, Wainstein J, Josse R, Lachin JM, Engel SS, Patel K, Peterson ED, Holman RR; TECOS Study Group. Pancreatic Safety of Sitagliptin in the TECOS Study. Diabetes Care. 2017 Feb;40(2):164-170. doi: 10.2337/dc15-2780. Epub 2016 Sep 14.
- McGuire DK, Van de Werf F, Armstrong PW, Standl E, Koglin J, Green JB, Bethel MA, Cornel JH, Lopes RD, Halvorsen S, Ambrosio G, Buse JB, Josse RG, Lachin JM, Pencina MJ, Garg J, Lokhnygina Y, Holman RR, Peterson ED; Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS) Study Group. Association Between Sitagliptin Use and Heart Failure Hospitalization and Related Outcomes in Type 2 Diabetes Mellitus: Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2016 May 1;1(2):126-35. doi: 10.1001/jamacardio.2016.0103.
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Completed
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14671
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14000
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March 30, 2015
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March 30, 2015 (Final data collection date for primary outcome measure)
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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
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Sexes Eligible for Study: |
All |
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50 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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Not Provided
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Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czech Republic, Estonia, Finland, France, Germany, Hong Kong, Hungary, India, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Malaysia, Netherlands, New Zealand, Norway, Poland, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
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NCT00790205
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0431-082 2008_523 ( Other Identifier: Merck study number ) 2008-006719-20 ( EudraCT Number )
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Yes
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Not Provided
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Plan to Share IPD: |
Yes |
Plan Description: |
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf |
URL: |
http://engagezone.msd.com/ds_documentation.php |
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Merck Sharp & Dohme LLC
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Executive Vice President, Clinical and Quantitative Sciences, Merck & Co., Inc.
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Merck Sharp & Dohme LLC
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Same as current
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Duke Clinical Research Institute, Oxford Diabetes Trials Unit
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Study Director: |
Medical Director |
Merck Sharp & Dohme LLC |
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Merck Sharp & Dohme LLC
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October 2021
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