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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02377388
Recruitment Status : Recruiting
First Posted : March 3, 2015
Last Update Posted : April 1, 2020
Sponsor:
Collaborator:
InCor Heart Institute
Information provided by (Responsible Party):
University of Sao Paulo General Hospital

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.


Condition or disease Intervention/treatment Phase
Platelet Aggregation During Acute Myocardial Infarction Drug: sitagliptin OR saxagliptin Drug: placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: DPP-4 Inhibitors in Patients With Type 2 Diabetes and Acute Myocardial Infarction:Effects on Platelet Function
Actual Study Start Date : February 7, 2017
Estimated Primary Completion Date : May 31, 2020
Estimated Study Completion Date : May 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

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 Name: 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 Name: PBO




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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 .


Other Outcome Measures:
  1. 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).

  2. 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

  3. 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 %


  4. 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).

  5. 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.

  6. 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 .


  7. 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).

  8. cholesterylester transfer protein(CETP) mass [ Time Frame: baseline ]
    Analysis of CETP mass between two arms.

  9. 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.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02377388


Contacts
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Contact: Paulo R Genestreti, MD 551126615058 paulo.gen@ig.com.br

Locations
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Brazil
Heart Institute(InCor)-Acute Coronary Care Unit Recruiting
São Paulo, SP, Brazil, 01406000
Contact: Paulo R Genestreti, MD    55 11 2661-5058    paulo.gen@ig.com.br   
Principal Investigator: Jose C Nicolau, MD,PhD         
Sub-Investigator: Paulo R Genestreti, MD         
Sponsors and Collaborators
University of Sao Paulo General Hospital
InCor Heart Institute
Investigators
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Principal Investigator: Jose C Nicolau, MD,PhD Heart Institute(InCor)-University of São Paulo GH-Medical School
Publications:
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, Menasché 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.

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Responsible Party: University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier: NCT02377388    
Other Study ID Numbers: University of São Paulo GH
First Posted: March 3, 2015    Key Record Dates
Last Update Posted: April 1, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by University of Sao Paulo General Hospital:
diabetes mellitus
platelet function testing
acute coronary syndromes
saxagliptin
sitagliptin
dpp-4 inhibitors
Additional relevant MeSH terms:
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Myocardial Infarction
Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Sitagliptin Phosphate
Saxagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action