The Association Between Platelet Inhibition and Perioperative Major Adverse Cardiac Events In Post-Percutaneous Coronary Intervention (PCI) Patients Undergoing Non-Cardiac Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Anesthesia Patient Safety Foundation
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01707459
First received: December 12, 2011
Last updated: October 4, 2013
Last verified: October 2013
  Purpose

This prospective, multicentre, observational study aims to test pre-operative platelet function when taking anti-platelet medications. The investigators are using a simple bedside blood test called Thromboelastography (TEG) and Platelet Mapping Assay (PMA). The investigators will then follow the patient throughout their hospital stay for any major cardiac complications (MACE) after surgery (peri-operative). The investigators hope to determine if there is an association between how well platelets were inhibited by these drugs before surgery and MACE during the perioperative period, 30 day, and one year follow-up. Also, the response of various people to anti-platelet medications and their chances of getting a major adverse cardiac outcome are determined by their genetic makeup. The investigators will try to determine if certain genes are associated with higher cardiac risk.

Hypothesis: In patients who had percutaneous coronary intervention (PCI) and are undergoing non-cardiac surgery (NCS) major adverse cardiac events (MACE) are associated with inadequate platelet inhibition.


Condition
Thrombosis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Association Between Platelet Inhibition and Perioperative Major Adverse Cardiac Events In Post-Percutaneous Coronary Intervention (PCI) Patients Undergoing Non-Cardiac Surgery

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Number of patients with major adverse cardiac event (MACE) [ Time Frame: Measure will occure every day for 5 postoperative days ] [ Designated as safety issue: No ]

    ECG daily for five days postoperatively Troponin measurements every 8 h +/- 1h for 6 measurements (first 48 hours postoperatively) then once daily till the fifth postoperative day.

    Patients will be assessed daily by study personnel for the presence of MACE (defined as death, ST or non-ST elevation myocardial infarction [MI], stent thrombosis or the need for repeat revascularization [PCI or coronary artery bypass grafting]transfusions, or the presence of bleeding complications.



Biospecimen Retention:   Samples With DNA

TEG-PMA and gene polymorphism analysis on blood samples


Estimated Enrollment: 250
Study Start Date: March 2010
Estimated Study Completion Date: August 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Detailed Description:

Data analysis: The participants' demographics, preoperative characteristics and postoperative information will be summarized using descriptive statistics: expressed as mean (standard deviation) or median (minimum, maximum, interquartile range) for continuous variables and number (percent) for categorical variables. We will initially use restricted cubic spline plots to evaluate the nature of the association of platelet inhibition (continuous variable) and the risk of MACE (logit transformation). Based upon these results, we will determine if percent inhibition can be treated as a continuous variable, or whether it can be categorized along specific cut-offs. We will also compare these results against a receiver-operating-characteristic curve analysis. Once we have determined the appropriate approach for describing percent platelet inhibition, univariate analyses will be performed with chi-square or Fishers' exact test for categorical data, and t-test and Mann-Whitney U test for continuous data. A p < 0.05 will be considered statistically significant. Random effect multivariable logistic regression will be used to assess the adjusted association of platelet inhibition with MACE during the perioperative period.46 This regression model will employ a random intercept for each center, so as to minimize the bias due to any confounding by center.47 Regression models will be constructed to selectively include the potentially confounding perioperative variables that are associated with a higher risk of MACE (as identified from the literature and clinical experience).7-12 In addition to platelet inhibition (preoperative value or change), four covariates will be included in the model: type of stent; time between PCI and NCS; mono-, dual (aspirin or aspirin and clopidogrel) or no therapy until the day of surgery; and urgent surgery. Since the recommended range of platelet inhibition (20-50%)was never validated during the perioperative period we will describe it as a continuous variable (0-100%).

Primary analysis will be as per protocol the secondary analysis will include patients who have incomplete data i.e. discharged early or refused one or more TEG samples.

Sample Size: The sample size estimations were based on comparison of platelet inhibition (measures as a continuous variable) between individuals who did or did not suffer MACE. We assumed that the difference between the MACE and non-MACE groups with regard to platelet inhibition would correspond to a medium Cohen's effect size (0.5 SD; i.e. difference in means equaling 0.5 of the pooled standard deviation). Based on the assumption of the medium effect size difference, an expected 20% rate of MACE, a 2-sided alpha of 0.05, 90 % power, and a 10% dropout rate, we would need 189 patients in total. In addition, since our planned statistical model involves logistic regression with a total of five covariates (platelet inhibition value; stent type; emergency surgery; time between PCI and NCS; mono-, dual or no therapy after PCI [aspirin vs. aspirin and clopidogrel or no medications]) the sample size estimate would still have approximately 8 events per included covariate in the regression model. To minimize bias in the regression model, estimates recommend the minimum number of outcomes per covariate is 5-10.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients who have coronary stents and undergoing non-cardiac surgery

Criteria

Inclusion Criteria:

  • Scheduled for non-cardiac surgery
  • Has had PCI with: BMS within the last 24 months OR DES within any time frame

Exclusion criteria:

  • Lack of informed consent
  • Known clotting abnormality affecting any part of the clotting cascade
  • Liver dysfunction with co-existing thrombocytopenia or INR > 1.4
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01707459

Locations
Canada, Ontario
Toronto General Hospital
Toronto, Ontario, Canada
Sponsors and Collaborators
University Health Network, Toronto
Anesthesia Patient Safety Foundation
Investigators
Principal Investigator: Marcin Wasowicz, MD Toronto General Hospital, University Health Network
  More Information

No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01707459     History of Changes
Other Study ID Numbers: UHN090090BE
Study First Received: December 12, 2011
Last Updated: October 4, 2013
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
platelet function
perioperative complications
major adverse cardiac events (MACE)
thromboelastography
polymorphism analysis
coronary stents
non-cardiac surgery

Additional relevant MeSH terms:
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 18, 2014