Multiple Daily Doses Of Aspirin To Overcome Aspirin Hyporesponsiveness Post Cardiac Bypass Surgery (ASACABG)
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.
Studie Overzicht
Toestand
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 2
Contacten en locaties
Studie Locaties
-
-
Ontario
-
Hamilton, Ontario, Canada, L8L2X2
- Hamilton General Hospital
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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)
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Dubbele
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Actieve vergelijker: Aspirin 81mg daily
Patients will receive 81mg daily during the postoperative period.
|
Aspirine 81 mg po dagelijks x 7 dagen of einde ziekenhuisopname.
Eerste dosis toegediend op dag 1 na de operatie.
Aspirine 325 mg po dagelijks x 7 dagen of einde ziekenhuisopname.
Eerste dosis toegediend op dag 1 na de operatie.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
|
|
Actieve vergelijker: Aspirine 325 mg per dag
Patiënten krijgen dagelijks 325 mg tijdens de postoperatieve periode, tot dag 7 postop of het einde van de ziekenhuisopname.
|
Aspirine 81 mg po dagelijks x 7 dagen of einde ziekenhuisopname.
Eerste dosis toegediend op dag 1 na de operatie.
Aspirine 325 mg po dagelijks x 7 dagen of einde ziekenhuisopname.
Eerste dosis toegediend op dag 1 na de operatie.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
|
|
Experimenteel: Aspirin 81mg four times daily
Patients will receive ASA 81mg four times daily until postoperative day 7 or end of hospitalization
|
Aspirine 81 mg po dagelijks x 7 dagen of einde ziekenhuisopname.
Eerste dosis toegediend op dag 1 na de operatie.
Aspirine 325 mg po dagelijks x 7 dagen of einde ziekenhuisopname.
Eerste dosis toegediend op dag 1 na de operatie.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
|---|---|
|
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
Tijdsspanne: Postoperative Day 4
|
Postoperative Day 4
|
Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
|---|---|
|
Arachidonzuur-geïnduceerde lichttransmissie-aggregometrie (LTA): Aggregatie wordt uitgedrukt als de maximale procentuele verandering in lichttransmissie ten opzichte van de uitgangswaarde, waarbij bloedplaatjes-arm plasma als referentie wordt gebruikt.
Tijdsspanne: Postoperatieve Dag 4
|
Postoperatieve Dag 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).
Tijdsspanne: Postoperative Day 4
|
Postoperative Day 4
|
|
DNA genetic analyses for single nucleotide polymorphisms
Tijdsspanne: A single preoperative blood sample was drawn (on average of 1 week prior to surgery)
|
A single preoperative blood sample was drawn (on average of 1 week prior to surgery)
|
Medewerkers en onderzoekers
Onderzoekers
- Hoofdonderzoeker: Jeremy Paikin, MD, Cardiology Fellow
- Hoofdonderzoeker: John Eikelboom, MBBS, Hematologist, PHRI researcher
- Hoofdonderzoeker: Richard Whitlock, MD, Cardiac Surgeon, PHRI researcher
- Hoofdonderzoeker: Guillaume Pare, MD, Medical Biochemist, PHRI researcher
- Studie stoel: Jack Hirsh, MD, Hematologist, Professor Emeritus, PHRI researcher
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Agenten van het perifere zenuwstelsel
- Enzymremmers
- Pijnstillers
- Sensorische systeemagenten
- Ontstekingsremmers, niet-steroïde
- Pijnstillers, niet-narcotisch
- Ontstekingsremmende middelen
- Antireumatische middelen
- Fibrinolytische middelen
- Fibrine modulerende middelen
- Bloedplaatjesaggregatieremmers
- Cyclo-oxygenaseremmers
- Antipyretica
- Aspirine
Andere studie-ID-nummers
- NIF-11271
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .