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

University of Sao Paulo General Hospital

Status and phase: Completed; Phase 3

Conditions: Platelet Aggregation During Acute Myocardial Infarction

Treatments: Drug: placebo; Drug: sitagliptin OR saxagliptin

Study type: Interventional

Funder types: Other

Identifiers

NCT02377388

University of São Paulo GH

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 74 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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74 participants in 2 patient groups, including a placebo group

treatment: DPP4 -i

Active Comparator group

Description:

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)

Treatment:

Drug: sitagliptin OR saxagliptin

control

Placebo Comparator group

Description:

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

Treatment:

Drug: placebo