Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 37 of 1302 for:    ASPIRIN AND Platelet Aggregation

Impact of Hybrid Coronary Revascularization on Antiplatelet Therapy

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02293928
Recruitment Status : Completed
First Posted : November 19, 2014
Last Update Posted : November 19, 2014
Sponsor:
Collaborators:
Danish Heart Foundation
Aase and Ejnar Danielsens Foundation
Information provided by (Responsible Party):
Ivy Modrau, Aarhus University Hospital Skejby

Tracking Information
First Submitted Date November 13, 2014
First Posted Date November 19, 2014
Last Update Posted Date November 19, 2014
Study Start Date October 2010
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 13, 2014)
Change in aspirin antiplatelet effect from preoperative to three days postoperative [ Time Frame: 12-14 days ]
Platelet aggregation measured by VerifyNow® Aspirin and Multiplate® Analyzer
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: November 13, 2014)
  • Change on aspirin antiplatelet effect from 3 days postoperative to 1 year follow-up [ Time Frame: 1 year ]
    Platelet aggregation measured by VerifyNow® Aspirin and Multiplate® Analyzer
  • Change on clopidogrel antiplatelet effect from first day after PCI to 1 year follow-up [ Time Frame: 1 year ]
    Platelet aggregation measured by VerifyNow®P2Y12 and Multiplate® Analyzer
  • Association between baseline platelet aggregation (off-aspirin) and aspirin antiplatelet effect [ Time Frame: 12-14 days ]
    Platelet aggregation measured by VerifyNow® Aspirin and Multiplate® Analyzer Baseline aggregation is compared to aggragation preoperatively (on maintenance aspirin treatment) and postoperatively (when aspirin is resumed).
  • Correlation between acute phase reactants and platelet aggregation [ Time Frame: 8-10 days preoperative until 1 year postoperative ]
    C-reactive protein, von Willebrand factor (antigen), and coagulation factor VIII (functional)
  • Correlation between platelet turnover and platelet aggregation [ Time Frame: 8-10 days preoperative until 1 year postoperative ]
    Platelet turnover assessed by Complete blood counts, including immature platelet fraction, immature platelet count, mean platelet volume and thrombopoietin.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 13, 2014)
  • Compliance to aspirin treatment at enrollment [ Time Frame: 8-10 days preoperative ]
    measured by levels of serum thromboxane B2 below 30 ng/ml
  • Compliance to aspirin treatment at 1 year follow-up [ Time Frame: 1 year ]
    measured by levels of serum thromboxane B2 below 30 ng/ml
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Impact of Hybrid Coronary Revascularization on Antiplatelet Therapy
Official Title Impact of Hybrid Coronary Revascularization on Antiplatelet Effect of Aspirin and Clopidogrel
Brief Summary

The effect of antiplatelet therapy is impaired among patients, who recently underwent on-pump coronary artery bypass grafting. The impact of hybrid coronary revascularization using minimal invasive surgical techniques on the antiplatelet effect of aspirin and clopidogrel remains unclear.

The aim of the study is to describe the impact of hybrid coronary revascularization on the effect of aspirin and clopidogrel. Furthermore, we will investigate whether high baseline platelet aggregation, high postoperative levels of platelet turnover and acute-phase response may contribute to the effect.

Detailed Description

Objective:

The effect of antiplatelet therapy is impaired among patients, who recently underwent on-pump coronary artery bypass grafting. The impact of hybrid coronary revascularization using minimal invasive surgical techniques on the antiplatelet effect of aspirin and clopidogrel remains unclear.

We hypothesize that hybrid coronary revascularization is associated with a transiently reduced antiplatelet effect of aspirin and clopidogrel. We hypothesize that the reduced antiplatelet effect of aspirin and clopidogrel could be explained by increased platelet turnover with an increased fraction of immature platelets in the peripheral blood. Furthermore, we hypothesize that the reduced antiplatelet effect is associated with increased inflammatory markers in the early postoperative phase. We hypothesize, that high platelet aggregation prior to the intervention is associated with reduced effect of antiplatelet therapy following hybrid coronary revascularization.

Methods:

40 patients with coronary artery disease will be enrolled in this prospective cohort study (recruited from a prospective pilot study conducted to assess feasibility and safety of hybrid coronary revascularization combining minimally invasive off-pump coronary artery bypass grafting through an inferior J-hemisternotomy (JOPCAB) with percutaneous coronary intervention - Clinicaltrials.gov identifier: NCT01496664). Demographics and medical history are documented preoperatively. The predicted mortality is assessed by means of the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) I. Adverse cardiovascular events are recorded prospectively, including graft dysfunction, myocardial infarction, stroke, and pulmonary embolism.

Six blood samples are obtained from each patient:

  • Pre-OP: in the outpatient setting while patients were on aspirin 75 mg daily
  • Baseline: in the morning prior to surgery after eight to ten days of aspirin discontinuation (off-aspirin)
  • Post-OP: on the first postoperative day when aspirin had been resumed
  • Pre-PCI: on the day prior to PCI
  • Post-PCI: on the first day after PCI following initiation of dual antiplatelet therapy
  • 1-year follow-up: when patients were still on maintenance aspirin 75 mg and clopidogrel 75 mg Platelet function analyses are performed using Multiplate® Analyzer (Roche, Roche Diagnostics, Mannheim, Germany), VerifyNow® Aspirin, and VerifyNow® P2Y12 (Accumetrics Inc., San Diego, CA, USA). For Multiplate® Analyzer, arachidonic acid (1.0 mM) and adenosine diphosphate (6.4 and 20 uM) are used as agonists.

Complete blood counts, including immature platelet fraction (IPF), immature platelet count (IPC), and mean platelet volume (MPV), are performed using a Sysmex XE-5000 haematology analyzer (Sysmex, Kobe, Japan) with upgraded software (XE IPF Master, Sysmex) enabling flow cytometric detection of the IPF. Enzyme-linked immunosorbent assays are used according to the manufacturers' instructions to measure serum thromboxane B2 (Cayman Chemical, Ann Arbor, MI, USA) and thrombopoietin (R&D Systems Europe, Abingdon, UK). Plasma C-reactive protein was measured by immunoprecipitation using the Cobas® 6000 (Roche, Basel, Switzerland). Von Willebrand factor (antigen) and coagulation factor VIII (functional) are measured using the ACL TOP (ILS Laboratories, Bedford, MA, USA).

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
4 ml serum and 4 ml sodium citrate plasma
Sampling Method Non-Probability Sample
Study Population Patients with coronary artery disease scheduled for elective hybrid coronary revascularization. The study cohort is recruited from a prospective pilot study conducted to assess feasibility and safety of hybrid coronary revascularization combining minimally invasive off-pump coronary artery bypass grafting and percutaneous coronary intervention (PCI) performed three to five days later (Clinicaltrials.gov identifier: NCT01496664).
Condition Coronary Artery Disease
Intervention Procedure: Hybrid coronary revascularization
Hybrid coronary revascularization with standard double antiplatelet therapy
Study Groups/Cohorts Elective hybrid coronary revascularization
All patients are treated with non-enteric coated aspirin 75 mg once daily prior to study participation. Aspirin treatment is discontinued 8-10 days prior to surgery and resumed 6-9 hours after surgery. Left internal mammary grafting of the left descendent coronary artery is performed off-pump through an inferior J-hemisternotomy (JOPCAB). All patients receive an oral loading dose of aspirin 300 mg 6-9 hours after surgery followed by daily maintenance doses of 75 mg aspirin. An oral loading dose of clopidogrel 300 mg 12 hours prior to PCI is followed by daily maintenance doses of 75 mg for 12 months. Patients are followed for 1 year.
Intervention: Procedure: Hybrid coronary revascularization
Publications * Modrau IS, Würtz M, Kristensen SD, Hvas AM. Reduced Effect of Aspirin and Clopidogrel Following Hybrid Coronary Revascularization. Clin Appl Thromb Hemost. 2015 Oct;21(7):603-11. doi: 10.1177/1076029615573304. Epub 2015 Mar 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: November 13, 2014)
40
Original Actual Enrollment Same as current
Actual Study Completion Date April 2013
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • symptomatic multivessel coronary artery disease
  • treatment with non-enteric coated aspirin 75 mg once daily

Exclusion Criteria:

  • aspirin or clopidogrel intolerance
  • conditions prohibitive of aspirin discontinuation prior to surgery
  • use of anticoagulants or any drugs other than aspirin known to affect platelet function
  • use of immunosuppressive drugs
  • platelet count <100 or >450 x 109/l
  • inability to give informed consent
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Denmark
Removed Location Countries  
 
Administrative Information
NCT Number NCT02293928
Other Study ID Numbers 10-000439
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Ivy Modrau, Aarhus University Hospital Skejby
Study Sponsor Aarhus University Hospital Skejby
Collaborators
  • Danish Heart Foundation
  • Aase and Ejnar Danielsens Foundation
Investigators
Principal Investigator: Ivy S Modrau, MD, DMSc Aarhus University Hospitak Skejby
PRS Account Aarhus University Hospital Skejby
Verification Date November 2014