Postoperative Dysfunction Following Cardiac SurgeryPhase 2NCT01902498
Multiple Daily Doses of Aspirin to Overcome Hyporesponsiveness Post Cardiac Bypass Surgery (ASACABG)- Part B
A Phase 2 study testing Aspirin in people with Postoperative Dysfunction Following Cardiac Surgery, run by Hamilton Health Sciences Corporation at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Postoperative Dysfunction Following Cardiac Surgery
- What is being tested?
- Aspirin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2013to Jul 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult subjects who undergo elective or urgent CABG surgery who are on or off aspirin during the preoperative period with or without valve replacement
Who cannot join
- initial platelet count <100,000
- receiving NSAIDs or other drugs that might interfere with aspirin's platelet-inhibitory effect
- clinically important bleeding (chest tube drainage >200ml/hr for 6hrs), or bleeding disorders that preclude the use of randomized therapies
- patients who do not provide informed written consent
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Being tested
- Aspirin
- Keywords
- aspirin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
Aspirin 81mg po daily x 7days or end of hospitalization. First dose administered on post op day 1.
AspirinDrug
Aspirin 325mg po daily x 7days or end of hospitalization. First dose administered on post op day 1.
AspirinDrug
Aspirin 162mg po twice daily x 7days or end of hospitalization. First dose administered on post op day 1.
| Study group | Role | What they receive |
|---|---|---|
| Aspirin 162mg twice daily | Experimental | Patients will receive 162mg twice daily during the postoperative period, until day 7 postop or the end of hospitalization. Receives: Drug: Aspirin |
| Aspirin 325mg daily | Active comparator | Patients will receive 325mg daily during the postoperative period, until day 7 postop or the end of hospitalization. Receives: Drug: Aspirin |
| Aspirin 81mg daily | Active comparator | Patients will receive 81mg daily during the postoperative period, until day 7 postop or the end of hospitalization. Receives: Drug: Aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum Thromboxane Concentration (ng/ml)
Measured: Postoperative Day 4
Secondary outcomes (2)
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.
Measured: Postoperative Day 4
DNA genetic analyses for single nucleotide polymorphisms
Measured: A single preoperative blood sample was drawn (on average 1 day prior to surgery)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2013 (estimated)
- Study startJul 2013
- Primary completionMar 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postoperative Dysfunction Following Cardiac SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hamilton Health Sciences Corporation
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jeremy Paikin, Hamilton Health Sciences Corporation
- Investigators
- Jeremy Paikin, MD, Principal investigator, Cardiology FellowJohn Eikelboom, MBBS, Principal investigator, Hematologist, PHRI researcherRichard Whitlock, MD, Principal investigator, Cardiac Surgeon, PHRI researcherGuillaume Pare, MD, Principal investigator, Medical Biochemist, PHRI researcherJack Hirsh, MD, Principal investigator, Hematologist, Professor Emeritus, PHRI researcher
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01902498
- Sponsor's protocol ID
- NIF-13324
- Status last verified
- Mar 2015
- First submitted
- 15 Jul 2013
- Last updated
- 19 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multiple Daily Doses of Aspirin to Overcome Hyporesponsiveness Post Cardiac Bypass Surgery (ASACABG)- Part B
- ClinicalTrials.gov ID
- NCT01902498
- Acronym / sponsor ID
- NIF-13324
- Keywords
- aspirin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Hamilton Health Sciences CorporationUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Mar 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 18 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Aspirin 162mg twice daily | Experimental | Drug: AspirinPatients will receive 162mg twice daily during the postoperative period, until day 7 postop or the end of hospitalization. |
| Aspirin 325mg daily | Active comparator | Drug: AspirinPatients will receive 325mg daily during the postoperative period, until day 7 postop or the end of hospitalization. |
| Aspirin 81mg daily | Active comparator | Drug: AspirinPatients will receive 81mg daily during the postoperative period, until day 7 postop or the end of hospitalization. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adult subjects who undergo elective or urgent CABG surgery who are on or off aspirin during the preoperative period with or without valve replacement
Key exclusion criteria (4 listed)
- initial platelet count <100,000
- receiving NSAIDs or other drugs that might interfere with aspirin's platelet-inhibitory effect
- clinically important bleeding (chest tube drainage >200ml/hr for 6hrs), or bleeding disorders that preclude the use of randomized therapies
- patients who do not provide informed written consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AspirinAspirin 81mg po daily x 7days or end of hospitalization. First dose administered on post op day 1. | Drug | Aspirin 162mg twice daily |
| AspirinAspirin 325mg po daily x 7days or end of hospitalization. First dose administered on post op day 1. | Drug | Aspirin 325mg daily |
| AspirinAspirin 162mg po twice daily x 7days or end of hospitalization. First dose administered on post op day 1. | Drug | Aspirin 81mg daily |
Primary outcome
Serum Thromboxane Concentration (ng/ml)
Time frame: Postoperative Day 4
2 secondary outcomes
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
DNA genetic analyses for single nucleotide polymorphisms
Time frame: A single preoperative blood sample was drawn (on average 1 day prior to surgery)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeremy Paikin, MD principal investigator
Cardiology Fellow
John Eikelboom, MBBS principal investigator
Hematologist, PHRI researcher
Richard Whitlock, MD principal investigator
Cardiac Surgeon, PHRI researcher
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aspirin in people with Postoperative Dysfunction Following Cardiac Surgery, run by Hamilton Health Sciences Corporation at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum Thromboxane Concentration (ng/ml) (time frame: Postoperative Day 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2015.