Clinical trial NCT02711124: Relationship Between Level of Hemoglobin A1c and Platelet Function in Patients Undergoing Cardiac Surgery
Official title: Relationship Between Level of Glycosylated Hemoglobin and Platelet Function in Patients Undergoing Coronary Artery Bypass Grafting
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Diabetes Mellitus
Complication of Coronary Artery Bypass Graft
Blood Platelet Disorders
Keywords: hemoglobin A1c
coronary artery bypass grafting
impedance aggregometry
platelet reactivity
clinical outcomes
Lead sponsor: Clinical Hospital Centre Zagreb
Sponsor class: OTHER
First posted: 2016-03-17
Enrollment: 130
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Study population are the diabetic patients undergoing coronary artery bypass grafting at the department of cardiac surgery (The University Hospital Centre Zagreb, Croatia).

The patients will be sampled in consecutive fashion. Cohort sample will be divided into two subgroups according to HbA1c level (Group 1 with HbA1c \< 7% and Group 2 with HbA1c ≥ 7%, respectively).

Brief summary: The aim of this study is to evaluate whether increased level of hemoglobin A1c (HbA1c) correlates to higher level of platelet reactivity assessed by impedance aggregometry in patients with diabetes mellitus undergoing elective coronary artery bypass grafting (CABG).

Detailed description: This study will be conducted at Cardiac Surgery Department, University Hospital Center Zagreb. It will be conducted in prospective observational fashion. Diabetic patients undergoing isolated, primary on-pump CABG will be consecutively recruited. Patients requiring urgent procedure will be excluded. Blood samples, both for conventional lab. findings (including HbA1c) and impedance aggregometry will be drawn prior to surgery and postoperatively on daily basis.

Cohort sample will be divided into two subgroups according to HbA1c level (Group 1 with HbA1c \< 7% and Group 2 with HbA1c ≥ 7%, respectively). Respective subgroups will be compared for basic demographic data, laboratory findings including those obtained using platelet function testing, and for clinical outcomes, respectively.

Multiple-electrode aggregometry:

Whole blood aggregation will be determined using a new-generation impedance aggregometer (Multiplate analyzer; Roche Diagnostics). In brief, when platelets expose receptors on their surface they get activated and stick on the Multiplate sensor wires enhancing the electrical resistance between them. An increase in impedance is expressed in arbitrary area under the curve (AUC) units. Platelet aggregation is determined in response to stimulation with arachidonic acid (ASPI (aspirin-sensitive patients identification) test designed to evaluate the effect to acetylsalicylic acid (ASA)) and adenosine diphosphate (ADP) (ADP test designed to evaluate the effect of thienopyridines, such as clopidogrel).

Eligibility criteria: Inclusion Criteria:

* Patients undergoing isolated primary on-pump CABG
* Elective surgery
* Diabetic patients including insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus NIDDM
* Patients on antiplatelet therapy (aspirin and/or clopidogrel) pre- and postoperatively

Exclusion Criteria:

* Missing consent
* Patients with cardiac surgical procedures other than isolated CABG
* Patients on antiplatelet therapy other than aspirin or clopidogrel
* Urgent surgery
* Off-pump CABG
* Redo CABG

Primary outcomes:
measure: The level of preoperative HbA1c that will be a predictor of the higher prevalence of platelet resistance to the aspirin
timeFrame: 4 days after surgery
Secondary outcomes:
measure: Differences in perioperative aspirin resistance (AUC, area under the curve) between patients with insulin-dependent diabetes mellitus and patients with non-insulin-dependent diabetes mellitus
timeFrame: 4 days after surgery
measure: Correlation between platelet ADP receptors reactivity (AUC) and the type of diabetes
timeFrame: 4 days after surgery
measure: Correlation of diabetes duration and platelet reactivity (AUC)
timeFrame: 4 days after surgery
measure: The prevalence of major adverse cardiovascular events (MAACE) in patients with HbA1c ≥ 7%
timeFrame: 3 months after surgery
measure: Postoperative thoracic drainage in patients with the appropriate glucose regulation (Hba1c<7%)
timeFrame: within the first 5 days after surgery
measure: Mortality
timeFrame: 3 months after surgery
measure: The level of HbA1c, that will represent the reliable predictor of platelet hyperreactivity and MAACE
timeFrame: within the 3 months after surgery
Other outcomes:
Locations:
city: Zagreb
country: Croatia
facility: The University Hospital Centre Zagreb, Department of cardiac surgery
Study officials:
name: Martina Zrno Mihaljević
role: PRINCIPAL_INVESTIGATOR
name: Bojan Biočina
role: STUDY_CHAIR
name: Mate Petričević
role: STUDY_DIRECTOR
References:
citation: Thourani VH, Weintraub WS, Stein B, Gebhart SS, Craver JM, Jones EL, Guyton RA. Influence of diabetes mellitus on early and late outcome after coronary artery bypass grafting. Ann Thorac Surg. 1999 Apr;67(4):1045-52. doi: 10.1016/s0003-4975(99)00143-5.
citation: Woods SE, Smith JM, Sohail S, Sarah A, Engle A. The influence of type 2 diabetes mellitus in patients undergoing coronary artery bypass graft surgery: an 8-year prospective cohort study. Chest. 2004 Dec;126(6):1789-95. doi: 10.1378/chest.126.6.1789.
citation: Lazar HL, Chipkin SR, Fitzgerald CA, Bao Y, Cabral H, Apstein CS. Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events. Circulation. 2004 Mar 30;109(12):1497-502. doi: 10.1161/01.CIR.0000121747.71054.79. Epub 2004 Mar 8.
citation: Furnary AP, Gao G, Grunkemeier GL, Wu Y, Zerr KJ, Bookin SO, Floten HS, Starr A. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003 May;125(5):1007-21. doi: 10.1067/mtc.2003.181.
citation: Halkos ME, Puskas JD, Lattouf OM, Kilgo P, Kerendi F, Song HK, Guyton RA, Thourani VH. Elevated preoperative hemoglobin A1c level is predictive of adverse events after coronary artery bypass surgery. J Thorac Cardiovasc Surg. 2008 Sep;136(3):631-40. doi: 10.1016/j.jtcvs.2008.02.091.
citation: Kempfert J, Anger K, Rastan A, Krabbes S, Lehmann S, Garbade J, Sauer M, Walther T, Dhein S, Mohr FW. Postoperative development of aspirin resistance following coronary artery bypass. Eur J Clin Invest. 2009 Sep;39(9):769-74. doi: 10.1111/j.1365-2362.2009.02175.x.
citation: Petricevic M, Biocina B, Konosic S, Burcar I, Siric F, Mihaljevic MZ, Ivancan V, Svetina L, Gasparovic H. Definition of acetylsalicylic acid resistance using whole blood impedance aggregometry in patients undergoing coronary artery surgery. Coll Antropol. 2013 Sep;37(3):833-9.
citation: Petricevic M, Biocina B, Konosic S, Kopjar T, Kunac N, Gasparovic H. Assessment of platelet function by whole blood impedance aggregometry in coronary artery bypass grafting patients on acetylsalicylic acid treatment may prompt a switch to dual antiplatelet therapy. Heart Vessels. 2013 Jan;28(1):57-65. doi: 10.1007/s00380-011-0216-3. Epub 2011 Dec 28.