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

August 26, 2020 updated by: University of Sao Paulo General Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

74

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • SP
      • São Paulo, SP, Brazil, 01406000
        • Heart Institute(InCor)-Acute Coronary Care Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: treatment: DPP4 -i

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
sitagliptin OR saxagliptin tablets, 48(+-24) hours after the beginning of an AMI,and both arms in use of dual anti-platelet therapy (DAPT) .
Other Names:
  • januvia ® OR onglyza ®
Placebo Comparator: control
placebo tablets identical to active comparator,administered according to GFR at randomization,during 30 days,OD
Drug: placebo
placebo tablets, 48(+-24) hours after the beginning of an AMI,and both arms in use of dual anti-platelet therapy (DAPT) .
Other Names:
  • PBO

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
changes on platelet aggregability.
Time Frame: baseline and 4(+-2) days after drug exposure.
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.
Time Frame: baseline and 30(+-5) days after drug exposure.
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.
Time Frame: baseline and 4 (+-2) days after drug exposure.
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.
Time Frame: baseline and 30(+-5) days after drug exposure.
Comparison on platelet aggregability by two different methods (Verify Now and Multiplate .
baseline and 30(+-5) days after drug exposure.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
changes in glycemic control(glycemic variability assessed by standard deviation(SD) of capillary glucose samples).
Time Frame: baseline up to 1 week.
Evaluated by measurements of capillary glucose samples by point-of care test during the length of coronary care unit(CCU) stay( expected average of 1 week).The glycemic variability will be obtained by calculating the standard deviation(SD).
baseline up to 1 week.
changes in glycemic control(glycemic variability assessed by continuous glucose monitoring system - CGM).
Time Frame: baseline and 48 (+-24) hours after drug exposure.
Evaluated by mean amplitude of glycemic excursions(MAGE) by the use of CGM
baseline and 48 (+-24) hours after drug exposure.
changes on platelet aggregability on pre-specified subgroups.
Time Frame: baseline and 4 (+-2)days after drug exposure.

Changes on platelet aggregability will be compared on pre-specified subgroups:

elderly (age >65 yrs-old) versus non-elderly;

male versus female;

smoking versus non-smoking patients;

obese(BMI>30 Kg/m2) versus non-obese;

length of diabetes;

baseline glucose;

glycated hemoglobin(HbA1c) < 9% and >9 %
baseline and 4 (+-2)days after drug exposure.
rate of hypoglycemia during coronary care unit stay.
Time Frame: baseline up to 1 week .
Rate of capillary glucose <70 mg/dL and <40 mg/dL,evaluated by capillary glucose measurements by point-of-care tests,during CCU stay(expected average of 1 week).
baseline up to 1 week .
total of insulin doses requirement during coronary care unit stay.
Time Frame: baseline up to 1 week .
Comparison of the total requirement of correctional insulin between treatment and control arms after drug exposure.
baseline up to 1 week .
incidence of composite end-point.
Time Frame: baseline and 30 (+-5) days after drug exposure

Comparison the incidence of composite end-point between two arms.Composite end-point include:

cardiovascular death;

unstable angina;

stroke ;

hospitalization for heart failure;

new non fatal myocardial infarction ;

coronary revascularization .
baseline and 30 (+-5) days after drug exposure
Infarct size.
Time Frame: baseline up to 1 week
Analysis of infarct size between two arms, by peak of creatine kinase(CK-MB) during CCU stay(expected average of 1 week).
baseline up to 1 week
cholesterylester transfer protein(CETP) mass
Time Frame: baseline
Analysis of CETP mass between two arms.
baseline
measure of safety, Number of participants with adverse effects by analysis on changes of serum level
Time Frame: baseline and 30(+-5) days after drug exposure.

Number of participants with adverse effects by analysis on changes of serum level of :

alanine transferase;

brain natriuretic peptide(BNP);

amylase;

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo General Hospital

Collaborators

InCor Heart Institute

Investigators

  • Principal Investigator: Jose C Nicolau, MD,PhD, Heart Institute(InCor)-University of São Paulo GH-Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 7, 2017

Primary Completion (Actual)

February 28, 2020

Study Completion (Actual)

February 28, 2020

Study Registration Dates

First Submitted

January 5, 2015

First Submitted That Met QC Criteria

March 2, 2015

First Posted (Estimate)

March 3, 2015

Study Record Updates

Last Update Posted (Actual)

August 28, 2020

Last Update Submitted That Met QC Criteria

August 26, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • University of São Paulo GH

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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