Multiple Daily Doses of Aspirin to Overcome Hyporesponsiveness Post Cardiac Bypass Surgery (ASACABG)- Part B

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Hamilton Health Sciences Corporation
Sponsor:
Information provided by (Responsible Party):
Jeremy Paikin, Hamilton Health Sciences Corporation
ClinicalTrials.gov Identifier:
NCT01902498
First received: July 15, 2013
Last updated: July 17, 2013
Last verified: July 2013
  Purpose

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 at blocking platelet activity than giving aspirin once daily.


Condition Intervention Phase
Postoperative Dysfunction Following Cardiac Surgery
Drug: Aspirin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multiple Daily Doses of Aspirin to Overcome Hyporesponsiveness Post Cardiac Bypass Surgery (ASACABG)- Part B

Resource links provided by NLM:


Further study details as provided by Hamilton Health Sciences Corporation:

Primary Outcome Measures:
  • Serum Thromboxane Concentration (ng/ml) [ Time Frame: Postoperative Day 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • DNA genetic analyses for single nucleotide polymorphisms [ Time Frame: A single preoperative blood sample was drawn (on average 1 day prior to surgery) ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: July 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aspirin 162mg twice daily
Patients will receive 162mg twice daily during the postoperative period, until day 7 postop or the end of hospitalization.
Drug: Aspirin
Aspirin 81mg po daily x 7days or end of hospitalization. First dose administered on post op day 1.
Active Comparator: Aspirin 325mg daily
Patients will receive 325mg daily during the postoperative period, until day 7 postop or the end of hospitalization.
Drug: Aspirin
Aspirin 325mg po daily x 7days or end of hospitalization. First dose administered on post op day 1.
Active Comparator: Aspirin 81mg daily
Patients will receive 81mg daily during the postoperative period, until day 7 postop or the end of hospitalization.
Drug: Aspirin
Aspirin 162mg po twice daily x 7days or end of hospitalization. First dose administered on post op day 1.

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 162mg BID 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 162mg bid 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Adult subjects who undergo elective or urgent CABG surgery who are on or off aspirin during the preoperative period with or without valve replacement

Exclusion Criteria:

  1. initial platelet count <100,000
  2. receiving NSAIDs or other drugs that might interfere with aspirin's platelet-inhibitory effect
  3. clinically important bleeding (chest tube drainage >200ml/hr for 6hrs), or bleeding disorders that preclude the use of randomized therapies
  4. patients who do not provide informed written consent
  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: NCT01902498

Contacts
Contact: Debi Sloane 905-527-4322 ext 40480 debi.sloane@phri.ca

Locations
Canada, Ontario
Hamilton General Hospital Recruiting
Hamilton, Ontario, Canada, L8L2X2
Contact: Debi Sloane    905-527-4322 ext 40408    debi.sloane@phri.ca   
Principal Investigator: Jeremy Paikin, MD         
Sponsors and Collaborators
Hamilton Health Sciences Corporation
Investigators
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
Principal Investigator: Jack Hirsh, MD Hematologist, Professor Emeritus, PHRI researcher
  More Information

No publications provided

Responsible Party: Jeremy Paikin, Principal Investigator, Hamilton Health Sciences Corporation
ClinicalTrials.gov Identifier: NCT01902498     History of Changes
Other Study ID Numbers: NIF-13324
Study First Received: July 15, 2013
Last Updated: July 17, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by Hamilton Health Sciences Corporation:
aspirin

Additional relevant MeSH terms:
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 22, 2014