Clinical trial NCT02377388: DPP-4 Inhibitors and Acute Myocardial Infarction:Effects on Platelet Function
Official title: DPP-4 Inhibitors in Patients With Type 2 Diabetes and Acute Myocardial Infarction:Effects on Platelet Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Platelet Aggregation During Acute Myocardial Infarction
Keywords: diabetes mellitus
platelet function testing
acute coronary syndromes
saxagliptin
sitagliptin
dpp-4 inhibitors
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
Collaborators: name: InCor Heart Institute
First posted: 2015-03-03
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: changes on platelet aggregability.
timeFrame: baseline and 4(+-2) days after drug exposure.
Secondary outcomes:
measure: changes on platelet aggregability.
timeFrame: baseline and 30(+-5) days after drug exposure.
measure: platelet aggregability differences by two point-of-care methods.
timeFrame: baseline and 4 (+-2) days after drug exposure.
measure: platelet aggregability differences by two point-of-care methods.
timeFrame: baseline and 30(+-5) days after drug exposure.
Other outcomes:
measure: changes in glycemic control(glycemic variability assessed by standard deviation(SD) of capillary glucose samples).
timeFrame: baseline up to 1 week.
measure: changes in glycemic control(glycemic variability assessed by continuous glucose monitoring system - CGM).
timeFrame: baseline and 48 (+-24) hours after drug exposure.
measure: changes on platelet aggregability on pre-specified subgroups.
timeFrame: baseline and 4 (+-2)days after drug exposure.
measure: rate of hypoglycemia during coronary care unit stay.
timeFrame: baseline up to 1 week .
measure: total of insulin doses requirement during coronary care unit stay.
timeFrame: baseline up to 1 week .
measure: incidence of composite end-point.
timeFrame: baseline and 30 (+-5) days after drug exposure
measure: Infarct size.
timeFrame: baseline up to 1 week
measure: cholesterylester transfer protein(CETP) mass
timeFrame: baseline
measure: measure of safety, Number of participants with adverse effects by analysis on changes of serum level
timeFrame: baseline and 30(+-5) days after drug exposure.
Locations:
city: São Paulo
country: Brazil
facility: Heart Institute(InCor)-Acute Coronary Care Unit
state: SP
Study officials:
affiliation: Heart Institute(InCor)-University of São Paulo GH-Medical School
name: Jose C Nicolau, MD,PhD
role: PRINCIPAL_INVESTIGATOR
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