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Multiple Daily Doses Of Aspirin To Overcome Aspirin Hyporesponsiveness Post Cardiac Bypass Surgery (ASACABG)

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ClinicalTrials.gov Identifier: NCT01618006
Recruitment Status : Completed
First Posted : June 13, 2012
Last Update Posted : March 19, 2015
Sponsor:
Information provided by (Responsible Party):
Jeremy Paikin, Hamilton Health Sciences Corporation

Tracking Information
First Submitted Date  ICMJE June 1, 2012
First Posted Date  ICMJE June 13, 2012
Last Update Posted Date March 19, 2015
Study Start Date  ICMJE January 2012
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 11, 2012)
Serum Thromboxane: Define an inadequate aspirin response as a value >0.69 ng/ml, which is 2 SD above the mean of aspirin-treated patients [ Time Frame: Postoperative Day 4 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01618006 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2012)
  • Arachidonic Acid Induced Light Transmission Aggregometry (LTA): Aggregation will be expressed as the maximum percent change in light transmittance from baseline, with platelet-poor plasma used as a reference. [ Time Frame: Postoperative Day 4 ]
  • Arachidonic Acid Induced Multiple Electrode Platelet Aggregometry (MEA):Aggregation was recorded for 6 minutes and will be reported as the area under the curve (aggregation units x min). [ Time Frame: Postoperative Day 4 ]
  • DNA genetic analyses for single nucleotide polymorphisms [ Time Frame: A single preoperative blood sample was drawn (on average of 1 week prior to surgery) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Multiple Daily Doses Of Aspirin To Overcome Aspirin Hyporesponsiveness Post Cardiac Bypass Surgery
Official Title  ICMJE Multiple Daily Doses Of Aspirin To Overcome Aspirin Hyporesponsiveness Post Cardiac Bypass Surgery
Brief Summary

Cardiac bypass surgery is an important treatment for patients with severely blocked arteries (tubes that delivery oxygen and nutrients to the heart). Hundreds of thousands of these operations are done each year to help relieve patients' chest pain and to prevent future heart attacks. The surgery is done by "bypassing" blood flow around badly clogged arteries by sewing on healthy vessels from another part of the body (usually from the leg or the chest). Aspirin (a blood thinner) is given to patients once a day after their surgery because it stops "sticky" cells in the blood (platelets) from blocking these new vessels (which may lead to a future heart attack).

Research has shown that aspirin does not work as well in people after they have bypass surgery as the investigators might expect (for reasons that are not fully understood). One reason aspirin may not work as well after surgery is because the body makes many more platelets after surgery than it would under normal circumstances. All of these new platelets overwhelm the aspirin and continue to be "sticky" and ready to block off arteries. The investigators believe that giving multiple daily doses of aspirin following bypass surgery is more effective than giving aspirin once daily at blocking platelet activity.

Detailed Description

Background:

Cardiovascular disease caused by athero-thrombosis is the number one cause of long-term morbidity and death worldwide. Many patients with advanced coronary disease benefit from Coronary Artery Bypass Graft (CABG) by improving symptoms and increasing their longevity.

However, the benefits of CABG surgery are attenuated by early graft failure. The administration of aspirin in the post-operative period has been shown in randomized controlled trials (RCT) to reduce the risk of graft occlusion, although rates remain unacceptably high. Patients undergoing CABG surgery transiently develop aspirin resistance, which likely contributes to vein graft failure.

The investigators believe the aspirin resistance is a consequence of rapid platelet turnover in the early postoperative period, resulting in a large number of platelets unexposed to aspirin (due to its short half life). The investigators hypothesize that by increasing the frequency of aspirin dosing, the investigators can reverse the aspirin resistance encountered post CABG surgery. The investigators are proposing a RCT comparing two different doses of aspirin (81mg and 325mg daily) to 81mg qid to determine whether multiple daily dosing can overcome aspirin resistance.

(1)Given that platelet production is increased many-fold after CABG surgery (and the short half-life of aspirin), the investigators hypothesize that increasing the frequency of aspirin dosing will lead to the acetylation of a greater number of platelets over the course of the day leading to an improved antiplatelet effect (as measured by serum thromboxane and platelet aggregation assays); (2) The investigators will examine three platelet-related single nucleotide polymorphisms (SNP) that have been implicated in aspirin hyporesponsiveness.

The investigators are proposing a single centre, randomized, open-label, RCT in 60 patients undergoing elective or urgent CABG surgery, to receive ASA 81mg daily, 325mg daily or 81 mg qid starting day 1 post-operatively. All patients will receive 325mg 6hrs following the procedure (day of operation) as long as there is no contraindication for antiplatelet therapy (ie significant bleeding) - as per the investigators centre's standard clinical practice. Further details on aspirin administration and outcome measurements are reported below.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Postoperative; Dysfunction Following Cardiac Surgery
Intervention  ICMJE
  • Drug: Aspirin
    Aspirin 81mg po daily x 7days or end of hospitalization. First dose administered on post op day 1.
  • Drug: Aspirin
    Aspirin 325mg po daily x 7days or end of hospitalization. First dose administered on post op day 1.
  • Drug: Aspirin
    Aspirin 81mg po four times daily x 7days or end of hospitalization. First dose administered on post op day 1.
Study Arms  ICMJE
  • Active Comparator: Aspirin 81mg daily
    Patients will receive 81mg daily during the postoperative period.
    Intervention: Drug: Aspirin
  • Active Comparator: Aspirin 325mg daily
    Patients will receive 325mg daily during the postoperative period, until day 7 postop or the end of hospitalization.
    Intervention: Drug: Aspirin
  • Experimental: Aspirin 81mg four times daily
    Patients will receive ASA 81mg four times daily until postoperative day 7 or end of hospitalization
    Intervention: Drug: Aspirin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 18, 2015)
120
Original Estimated Enrollment  ICMJE
 (submitted: June 11, 2012)
60
Actual Study Completion Date  ICMJE August 2013
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult subjects who undergo elective or urgent CABG surgery who are on or off aspirin during the preoperative period

Exclusion Criteria:

  • (a) initial platelet count <100,000 (b) significant liver disease (c) renal impairment (CrCl<30 ml/min/1.73 m2) (d) receiving (or planned) clopidogrel therapy (e) receiving NSAIDs or other drugs that might interfere with aspirin's platelet-inhibitory effect (f) need for therapeutic doses of parenteral or oral anticoagulants after surgery and (g) off-pump CABG (h) clinically important bleeding (chest tube drainage >200ml/hr for 6hrs)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01618006
Other Study ID Numbers  ICMJE NIF-11271
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jeremy Paikin, Hamilton Health Sciences Corporation
Study Sponsor  ICMJE Hamilton Health Sciences Corporation
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jeremy Paikin, MD Cardiology Fellow
Principal Investigator: John Eikelboom, MBBS Hematologist, PHRI researcher
Principal Investigator: Richard Whitlock, MD Cardiac Surgeon, PHRI researcher
Principal Investigator: Guillaume Pare, MD Medical Biochemist, PHRI researcher
Study Chair: Jack Hirsh, MD Hematologist, Professor Emeritus, PHRI researcher
PRS Account Hamilton Health Sciences Corporation
Verification Date March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP