DPP-4 Inhibitors and Acute Myocardial Infarction:Effects on Platelet Function

NCT02377388 | Completed Phase 3 DMC

• 1 other identifier: University of São Paulo GH
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

Cardiovascular events are the main cause of mortality in diabetic patients ,on the other hand,during an acute myocardial infarction(AMI),hyperglycemia increases mortality and is related to different pathophysiologic processes. More important evidence regarding the effect of glycemic control on AMI patients prognosis is contradictory,and the potential benefits of dipeptidyl peptidase-4 inhibitors(DPP4-i) in this setting is unknown. The aim of this study is to assess the presence of pleiotropic effects of DPP4-i(sitagliptin or saxagliptin) and their relationship with glycemic control during in-hospital phase of AMI.

Conditions

Platelet Aggregation During Acute Myocardial Infarction

Keywords

diabetes mellitus; platelet function testing; acute coronary syndromes; saxagliptin; sitagliptin; dpp-4 inhibitors

Outcome Measures

Primary Outcomes (1)

• changes on platelet aggregability.

  Comparison on platelet function between two therapeutic arms in a double-blind randomized fashion. Platelet aggregability will be measured 4(+-2) days after drug exposure,using a point-of-care test (VerifyNow Aspirin) in type 2 diabetic patients with AMI on dual antiplatelet therapy (ASA+ ticagrelor or clopidogrel according to institutional routine).

  baseline and 4(+-2) days after drug exposure.

Secondary Outcomes (3)

• changes on platelet aggregability.

  baseline and 30(+-5) days after drug exposure.

• platelet aggregability differences by two point-of-care methods.

  baseline and 4 (+-2) days after drug exposure.

• platelet aggregability differences by two point-of-care methods.

  baseline and 30(+-5) days after drug exposure.

Other Outcomes (9)

• changes in glycemic control(glycemic variability assessed by standard deviation(SD) of capillary glucose samples).

  baseline up to 1 week.

• changes in glycemic control(glycemic variability assessed by continuous glucose monitoring system - CGM).

  baseline and 48 (+-24) hours after drug exposure.

• changes on platelet aggregability on pre-specified subgroups.

  baseline and 4 (+-2)days after drug exposure.

Study Arms (2)

treatment: DPP4 -i

ACTIVE COMPARATOR

Use of DPP4-i : sitagliptin 50 mg (if glomerular filtration rate-GFR \<50 ml/min at randomization) or 100 mg (if GFR\>50 ml/min at randomization),during 30 days,once-daily(OD) OR saxagliptin 2,5 mg (if glomerular filtration rate-GFR \<50 ml/min at randomization) or 5 mg (if GFR\>50 ml/min at randomization),during 30 days,once-daily(OD)

Drug: sitagliptin OR saxagliptin

control

PLACEBO COMPARATOR

placebo tablets identical to active comparator,administered according to GFR at randomization,during 30 days,OD

Drug: placebo

Interventions

sitagliptin OR saxagliptin DRUG

sitagliptin OR saxagliptin tablets, 48(+-24) hours after the beginning of an AMI,and both arms in use of dual anti-platelet therapy (DAPT) .

Also known as: januvia ® OR onglyza ®

treatment: DPP4 -i

placebo DRUG

placebo tablets, 48(+-24) hours after the beginning of an AMI,and both arms in use of dual anti-platelet therapy (DAPT) .

Also known as: PBO

control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• previous diagnosis of type 2 diabetes mellitus,with treatment including insulin and/or oral antidiabetic agent;
• subjects without previous diagnosis of diabetes,but HbA1c admission \>= 6,5% during current hospital-stay
• AMI with or without ST-elevation;
• use of double antiplatelet therapy;
• signed informed consent term

You may not qualify if:

• GFR \<30 ml/min;
• use of DPP4 inhibitors or glucagon- like peptide-1(GLP1) analogue in the past 6 months;
• use of strong inhibitors of cytochrome P450(CYP3A4/5) ou glucocorticoids;
• severe systemic decompensation requiring insulin infusion;
• Killip classification of myocardial infarction grade \>2;
• previous history of pancreatitis

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead
• InCor Heart Institute: collaborator

Study Sites (1)

Heart Institute(InCor)-Acute Coronary Care Unit

São Paulo, São Paulo, 01406000, Brazil

Location

Related Publications (54)

• Kosiborod M, Rathore SS, Inzucchi SE, Masoudi FA, Wang Y, Havranek EP, Krumholz HM. Admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction: implications for patients with and without recognized diabetes. Circulation. 2005 Jun 14;111(23):3078-86. doi: 10.1161/CIRCULATIONAHA.104.517839. Epub 2005 Jun 6.

  PMID: 15939812 BACKGROUND

• Kosiborod M, Inzucchi SE, Krumholz HM, Xiao L, Jones PG, Fiske S, Masoudi FA, Marso SP, Spertus JA. Glucometrics in patients hospitalized with acute myocardial infarction: defining the optimal outcomes-based measure of risk. Circulation. 2008 Feb 26;117(8):1018-27. doi: 10.1161/CIRCULATIONAHA.107.740498. Epub 2008 Feb 11.

  PMID: 18268145 BACKGROUND

• Goyal A, Mahaffey KW, Garg J, Nicolau JC, Hochman JS, Weaver WD, Theroux P, Oliveira GB, Todaro TG, Mojcik CF, Armstrong PW, Granger CB. Prognostic significance of the change in glucose level in the first 24 h after acute myocardial infarction: results from the CARDINAL study. Eur Heart J. 2006 Jun;27(11):1289-97. doi: 10.1093/eurheartj/ehi884. Epub 2006 Apr 12.

  PMID: 16611669 BACKGROUND

• Nicolau JC, Maia LN, Vitola JV, Mahaffey KW, Machado MN, Ramires JA. Baseline glucose and left ventricular remodeling after acute myocardial infarction. J Diabetes Complications. 2007 Sep-Oct;21(5):294-9. doi: 10.1016/j.jdiacomp.2006.01.003.

  PMID: 17825753 BACKGROUND

• Nicolau JC, Serrano CV Jr, Giraldez RR, Baracioli LM, Moreira HG, Lima F, Franken M, Kalil R, Ramires JA, Giugliano RP. In patients with acute myocardial infarction, the impact of hyperglycemia as a risk factor for mortality is not homogeneous across age-groups. Diabetes Care. 2012 Jan;35(1):150-2. doi: 10.2337/dc11-1170. Epub 2011 Oct 25.

  PMID: 22028280 BACKGROUND

• Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006 Apr 12;295(14):1681-7. doi: 10.1001/jama.295.14.1681.

  PMID: 16609090 BACKGROUND

• Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002 Oct 15;106(16):2067-72. doi: 10.1161/01.cir.0000034509.14906.ae.

  PMID: 12379575 BACKGROUND

• Standl E, Schnell O, Ceriello A. Postprandial hyperglycemia and glycemic variability: should we care? Diabetes Care. 2011 May;34 Suppl 2(Suppl 2):S120-7. doi: 10.2337/dc11-s206.

  PMID: 21525442 BACKGROUND

• Hermanides J, Vriesendorp TM, Bosman RJ, Zandstra DF, Hoekstra JB, Devries JH. Glucose variability is associated with intensive care unit mortality. Crit Care Med. 2010 Mar;38(3):838-42. doi: 10.1097/CCM.0b013e3181cc4be9.

  PMID: 20035218 BACKGROUND

• Krinsley JS. Glycemic variability: a strong independent predictor of mortality in critically ill patients. Crit Care Med. 2008 Nov;36(11):3008-13. doi: 10.1097/CCM.0b013e31818b38d2.

  PMID: 18824908 BACKGROUND

• Lipska KJ, Venkitachalam L, Gosch K, Kovatchev B, Van den Berghe G, Meyfroidt G, Jones PG, Inzucchi SE, Spertus JA, DeVries JH, Kosiborod M. Glucose variability and mortality in patients hospitalized with acute myocardial infarction. Circ Cardiovasc Qual Outcomes. 2012 Jul 1;5(4):550-7. doi: 10.1161/CIRCOUTCOMES.111.963298. Epub 2012 Jun 12.

  PMID: 22693348 BACKGROUND

• Siegelaar SE, Kerr L, Jacober SJ, Devries JH. A decrease in glucose variability does not reduce cardiovascular event rates in type 2 diabetic patients after acute myocardial infarction: a reanalysis of the HEART2D study. Diabetes Care. 2011 Apr;34(4):855-7. doi: 10.2337/dc10-1684.

  PMID: 21447661 BACKGROUND

• Malmberg K, Ryden L, Efendic S, Herlitz J, Nicol P, Waldenstrom A, Wedel H, Welin L. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol. 1995 Jul;26(1):57-65. doi: 10.1016/0735-1097(95)00126-k.

  PMID: 7797776 BACKGROUND

• Malmberg K, Ryden L, Wedel H, Birkeland K, Bootsma A, Dickstein K, Efendic S, Fisher M, Hamsten A, Herlitz J, Hildebrandt P, MacLeod K, Laakso M, Torp-Pedersen C, Waldenstrom A; DIGAMI 2 Investigators. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J. 2005 Apr;26(7):650-61. doi: 10.1093/eurheartj/ehi199. Epub 2005 Feb 23.

  PMID: 15728645 BACKGROUND

• de Mulder M, Umans VA, Cornel JH, van der Zant FM, Stam F, Oemrawsingh RM, Akkerhuis KM, Boersma E. Intensive glucose regulation in hyperglycemic acute coronary syndrome: results of the randomized BIOMarker study to identify the acute risk of a coronary syndrome-2 (BIOMArCS-2) glucose trial. JAMA Intern Med. 2013 Nov 11;173(20):1896-904. doi: 10.1001/jamainternmed.2013.10074.

  PMID: 24018647 BACKGROUND

• NICE-SUGAR Study Investigators; Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hebert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009 Mar 26;360(13):1283-97. doi: 10.1056/NEJMoa0810625. Epub 2009 Mar 24.

  PMID: 19318384 BACKGROUND

• Griesdale DE, de Souza RJ, van Dam RM, Heyland DK, Cook DJ, Malhotra A, Dhaliwal R, Henderson WR, Chittock DR, Finfer S, Talmor D. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ. 2009 Apr 14;180(8):821-7. doi: 10.1503/cmaj.090206. Epub 2009 Mar 24.

  PMID: 19318387 BACKGROUND

• Kosiborod M, Inzucchi SE, Krumholz HM, Masoudi FA, Goyal A, Xiao L, Jones PG, Fiske S, Spertus JA. Glucose normalization and outcomes in patients with acute myocardial infarction. Arch Intern Med. 2009 Mar 9;169(5):438-46. doi: 10.1001/archinternmed.2008.593.

  PMID: 19273773 BACKGROUND

• Selker HP, Beshansky JR, Sheehan PR, Massaro JM, Griffith JL, D'Agostino RB, Ruthazer R, Atkins JM, Sayah AJ, Levy MK, Richards ME, Aufderheide TP, Braude DA, Pirrallo RG, Doyle DD, Frascone RJ, Kosiak DJ, Leaming JM, Van Gelder CM, Walter GP, Wayne MA, Woolard RH, Opie LH, Rackley CE, Apstein CS, Udelson JE. Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial. JAMA. 2012 May 9;307(18):1925-33. doi: 10.1001/jama.2012.426. Epub 2012 Mar 27.

  PMID: 22452807 BACKGROUND

• Desouza CV, Bolli GB, Fonseca V. Hypoglycemia, diabetes, and cardiovascular events. Diabetes Care. 2010 Jun;33(6):1389-94. doi: 10.2337/dc09-2082. No abstract available.

  PMID: 20508232 BACKGROUND

• Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Ramirez C, Sabate M, Jimenez-Quevedo P, Hernandez R, Moreno R, Escaned J, Alfonso F, Banuelos C, Costa MA, Bass TA, Macaya C. Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment. Diabetes. 2005 Aug;54(8):2430-5. doi: 10.2337/diabetes.54.8.2430.

  PMID: 16046311 BACKGROUND

• Alzahrani SH, Ajjan RA. Coagulation and fibrinolysis in diabetes. Diab Vasc Dis Res. 2010 Oct;7(4):260-73. doi: 10.1177/1479164110383723. Epub 2010 Sep 16.

  PMID: 20847109 BACKGROUND

• Park KW, Park JJ, Jeon KH, Kang SH, Oh IY, Yang HM, Cho HJ, Lee HY, Kang HJ, Koo BK, Oh BH, Park YB, Kim HS. Clinical predictors of high posttreatment platelet reactivity to clopidogrel in Koreans. Cardiovasc Ther. 2012 Feb;30(1):5-11. doi: 10.1111/j.1755-5922.2010.00249.x. Epub 2010 Dec 6.

  PMID: 21129165 BACKGROUND

• Demirtunc R, Duman D, Basar M, Bilgi M, Teomete M, Garip T. The relationship between glycemic control and platelet activity in type 2 diabetes mellitus. J Diabetes Complications. 2009 Mar-Apr;23(2):89-94. doi: 10.1016/j.jdiacomp.2008.01.006. Epub 2008 Mar 20.

  PMID: 18358749 BACKGROUND

• Singla A, Antonino MJ, Bliden KP, Tantry US, Gurbel PA. The relation between platelet reactivity and glycemic control in diabetic patients with cardiovascular disease on maintenance aspirin and clopidogrel therapy. Am Heart J. 2009 Nov;158(5):784.e1-6. doi: 10.1016/j.ahj.2009.08.013.

  PMID: 19853698 BACKGROUND

• Sanidas EA, Brener SJ, Maehara A, Genereux P, Witzenbichler B, El-Omar M, Fahy M, Mehran R, Gibson CM, Stone GW. Outcomes in diabetic patients undergoing primary percutaneous coronary intervention for acute anterior myocardial infarction: results from the INFUSE-AMI study. Catheter Cardiovasc Interv. 2014 Apr 1;83(5):704-10. doi: 10.1002/ccd.25203. Epub 2013 Oct 23.

  PMID: 24030863 BACKGROUND

• Lamanna C, Monami M, Marchionni N, Mannucci E. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2011 Mar;13(3):221-8. doi: 10.1111/j.1463-1326.2010.01349.x.

  PMID: 21205121 BACKGROUND

• Grant PJ. Beneficial effects of metformin on haemostasis and vascular function in man. Diabetes Metab. 2003 Sep;29(4 Pt 2):6S44-52. doi: 10.1016/s1262-3636(03)72787-6.

  PMID: 14502100 BACKGROUND

• Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001 Oct;108(8):1167-74. doi: 10.1172/JCI13505.

  PMID: 11602624 BACKGROUND

• De Caterina R, Madonna R, Sourij H, Wascher T. Glycaemic control in acute coronary syndromes: prognostic value and therapeutic options. Eur Heart J. 2010 Jul;31(13):1557-64. doi: 10.1093/eurheartj/ehq162. Epub 2010 Jun 2.

  PMID: 20519242 BACKGROUND

• Scheen AJ. DPP-4 inhibitors in the management of type 2 diabetes: a critical review of head-to-head trials. Diabetes Metab. 2012 Apr;38(2):89-101. doi: 10.1016/j.diabet.2011.11.001. Epub 2011 Dec 22.

  PMID: 22197148 BACKGROUND

• Phung OJ, Scholle JM, Talwar M, Coleman CI. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA. 2010 Apr 14;303(14):1410-8. doi: 10.1001/jama.2010.405.

  PMID: 20388897 BACKGROUND

• Karagiannis T, Paschos P, Paletas K, Matthews DR, Tsapas A. Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis. BMJ. 2012 Mar 12;344:e1369. doi: 10.1136/bmj.e1369.

  PMID: 22411919 BACKGROUND

• Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012 Jun;35(6):1364-79. doi: 10.2337/dc12-0413. Epub 2012 Apr 19. No abstract available.

  PMID: 22517736 BACKGROUND

• Jose T, Inzucchi SE. Cardiovascular effects of the DPP-4 inhibitors. Diab Vasc Dis Res. 2012 Apr;9(2):109-16. doi: 10.1177/1479164111436236. Epub 2012 Feb 15.

  PMID: 22337893 BACKGROUND

• Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev. 2012 Apr;33(2):187-215. doi: 10.1210/er.2011-1052. Epub 2012 Feb 8.

  PMID: 22323472 BACKGROUND

• Scheen AJ. Cardiovascular effects of dipeptidyl peptidase-4 inhibitors: from risk factors to clinical outcomes. Postgrad Med. 2013 May;125(3):7-20. doi: 10.3810/pgm.2013.05.2659.

  PMID: 23748503 BACKGROUND

• Rizzo MR, Barbieri M, Marfella R, Paolisso G. Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care. 2012 Oct;35(10):2076-82. doi: 10.2337/dc12-0199. Epub 2012 Jun 11.

  PMID: 22688551 BACKGROUND

• Gupta AK, Verma AK, Kailashiya J, Singh SK, Kumar N. Sitagliptin: anti-platelet effect in diabetes and healthy volunteers. Platelets. 2012;23(8):565-70. doi: 10.3109/09537104.2012.721907. Epub 2012 Sep 5.

  PMID: 22950787 BACKGROUND

• Khan S, Khan S, Imran M, Pillai KK, Akhtar M, Najmi AK. Effects of pioglitazone and vildagliptin on coagulation cascade in diabetes mellitus--targeting thrombogenesis. Expert Opin Ther Targets. 2013 Jun;17(6):627-39. doi: 10.1517/14728222.2013.764991. Epub 2013 Jan 28.

  PMID: 23356568 BACKGROUND

• Deacon CF. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes Metab. 2011 Jan;13(1):7-18. doi: 10.1111/j.1463-1326.2010.01306.x.

  PMID: 21114598 BACKGROUND

• Barnett AH, Charbonnel B, Donovan M, Fleming D, Chen R. Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin. Curr Med Res Opin. 2012 Apr;28(4):513-23. doi: 10.1185/03007995.2012.665046. Epub 2012 Mar 1.

  PMID: 22313154 BACKGROUND

• Frederich R, Alexander JH, Fiedorek FT, Donovan M, Berglind N, Harris S, Chen R, Wolf R, Mahaffey KW. A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2 diabetes. Postgrad Med. 2010 May;122(3):16-27. doi: 10.3810/pgm.2010.05.2138.

  PMID: 20463410 BACKGROUND

• Cobble ME, Frederich R. Saxagliptin for the treatment of type 2 diabetes mellitus: assessing cardiovascular data. Cardiovasc Diabetol. 2012 Jan 16;11:6. doi: 10.1186/1475-2840-11-6.

  PMID: 22248301 BACKGROUND

• Monami M, Dicembrini I, Martelli D, Mannucci E. Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials. Curr Med Res Opin. 2011 Nov;27 Suppl 3:57-64. doi: 10.1185/03007995.2011.602964.

  PMID: 22106978 BACKGROUND

• Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I; SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013 Oct 3;369(14):1317-26. doi: 10.1056/NEJMoa1307684. Epub 2013 Sep 2.

  PMID: 23992601 BACKGROUND

• Umpierrez GE, Gianchandani R, Smiley D, Jacobs S, Wesorick DH, Newton C, Farrokhi F, Peng L, Reyes D, Lathkar-Pradhan S, Pasquel F. Safety and efficacy of sitagliptin therapy for the inpatient management of general medicine and surgery patients with type 2 diabetes: a pilot, randomized, controlled study. Diabetes Care. 2013 Nov;36(11):3430-5. doi: 10.2337/dc13-0277. Epub 2013 Jul 22.

  PMID: 23877988 BACKGROUND

• American Diabetes Association. Executive summary: Standards of medical care in diabetes--2012. Diabetes Care. 2012 Jan;35 Suppl 1(Suppl 1):S4-S10. doi: 10.2337/dc12-s004. No abstract available.

  PMID: 22187471 BACKGROUND

• Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction; Katus HA, Lindahl B, Morrow DA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasche P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S. Third universal definition of myocardial infarction. Circulation. 2012 Oct 16;126(16):2020-35. doi: 10.1161/CIR.0b013e31826e1058. Epub 2012 Aug 24. No abstract available.

  PMID: 22923432 BACKGROUND

• Scirica BM, Braunwald E, Raz I, Cavender MA, Morrow DA, Jarolim P, Udell JA, Mosenzon O, Im K, Umez-Eronini AA, Pollack PS, Hirshberg B, Frederich R, Lewis BS, McGuire DK, Davidson J, Steg PG, Bhatt DL; SAVOR-TIMI 53 Steering Committee and Investigators*. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2014 Oct 28;130(18):1579-88. doi: 10.1161/CIRCULATIONAHA.114.010389. Epub 2014 Sep 4.

  PMID: 25189213 BACKGROUND

• Engel SS, Round E, Golm GT, Kaufman KD, Goldstein BJ. Safety and tolerability of sitagliptin in type 2 diabetes: pooled analysis of 25 clinical studies. Diabetes Ther. 2013 Jun;4(1):119-45. doi: 10.1007/s13300-013-0024-0. Epub 2013 May 23.

  PMID: 23700194 BACKGROUND

• Williams-Herman D, Round E, Swern AS, Musser B, Davies MJ, Stein PP, Kaufman KD, Amatruda JM. Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysis. BMC Endocr Disord. 2008 Oct 27;8:14. doi: 10.1186/1472-6823-8-14.

  PMID: 18954434 BACKGROUND

• 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.

  PMID: 26052984 BACKGROUND

• 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.

  PMID: 27437883 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus; Acute Coronary Syndrome

Interventions

Sitagliptin Phosphate; saxagliptin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Jose C Nicolau, MD,PhD

  Heart Institute(InCor)-University of São Paulo GH-Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2015
• First Posted: March 3, 2015
• Study Start: February 7, 2017
• Primary Completion: February 28, 2020
• Study Completion: February 28, 2020
• Last Updated: August 28, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share

Locations

BR (1)