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

Study Overview
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Brief Summary
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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.

Detailed Description
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Randomized clinical trial,double-blinded,placebo-controlled, in a single center, to assess the influence of DPP4-i on platelet aggregability in type 2 diabetic patients with acute myocardial infarction in use of dual anti platelet therapy (DAPT) . Others exploratory analysis include:glycemic control ,infarct size,genetic analysis and cholesterol metabolism. After giving signed informed consent,eligible subjects will be randomly allocated to receive saxagliptin or placebo, in the first 48 hours (+-24) after the beginning of an AMI. The investigator and subjects will be blinded to trial treatment,and a person not involved in trial conduct will prepare the doses of study drug.The doses will be administered by mouth,in a once daily basis by the investigator. Blood samples will be collected by the investigator according to pre-specified outcomes and time frames. Evaluation of glycemic control by CGM will be carried out by the investigator,including insert and withdrawal of the device. Treatment of the acute event,(AMI) will be done according to routine procedures from coronary care unit. Serious adverse event report taking into consideration all-cause mortality, cardiovascular mortality, hospitalization for heart failure and pancreatitis, will be done according to presence of these events.

Official Title
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DPP-4 Inhibitors in Patients With Type 2 Diabetes and Acute Myocardial Infarction:Effects on Platelet Function

Conditions
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Platelet Aggregation During Acute Myocardial Infarction

Intervention / Treatment
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* Drug: sitagliptin OR saxagliptin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: treatment: DPP4 -i<br>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<br>* sitagliptin OR saxagliptin tablets, 48(+-24) hours after the beginning of an AMI,and both arms in use of dual anti-platelet therapy (DAPT) .<br>* Other names: januvia ® OR onglyza ®;|
| Placebo Comparator: control<br>placebo tablets identical to active comparator,administered according to GFR at randomization,during 30 days,OD | Drug: placebo<br>* placebo tablets, 48(+-24) hours after the beginning of an AMI,and both arms in use of dual anti-platelet therapy (DAPT) .<br>* Other names: PBO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes on platelet aggregability. | Primary outcome measure analyzed at baseline and 30(+-5) days after drug exposure. | baseline and 30(+-5) days after drug exposure. | 
| platelet aggregability differences by two point-of-care methods. | Comparison on platelet aggregability by two different methods :Verify Now and Multiplate. | baseline and 4 (+-2) days after drug exposure. | 
| platelet aggregability differences by two point-of-care methods. | Comparison on platelet aggregability by two different methods (Verify Now and Multiplate . | baseline and 30(+-5) days after drug exposure. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes mellitus, platelet function testing, acute coronary syndromes, saxagliptin, sitagliptin, dpp-4 inhibitors