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.
Studieoversikt
Status
Intervensjon / Behandling
Detaljert beskrivelse
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
Registrering (Faktiske)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
-
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Ontario
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Hamilton, Ontario, Canada, L8L2X2
- Hamilton General Hospital
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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)
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Dobbelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Aktiv komparator: Aspirin 81mg daily
Patients will receive 81mg daily during the postoperative period.
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Aspirin 81mg po daglig x 7 dager eller slutten av sykehusinnleggelsen.
Første dose administrert på dag 1 etter operasjon.
Aspirin 325mg po daglig x 7 dager eller slutten av sykehusinnleggelsen.
Første dose administrert på dag 1 etter operasjon.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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Aktiv komparator: Aspirin 325mg daglig
Pasienter vil få 325 mg daglig i den postoperative perioden, frem til dag 7 postop eller slutten av sykehusinnleggelsen.
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Aspirin 81mg po daglig x 7 dager eller slutten av sykehusinnleggelsen.
Første dose administrert på dag 1 etter operasjon.
Aspirin 325mg po daglig x 7 dager eller slutten av sykehusinnleggelsen.
Første dose administrert på dag 1 etter operasjon.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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Eksperimentell: Aspirin 81mg four times daily
Patients will receive ASA 81mg four times daily until postoperative day 7 or end of hospitalization
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Aspirin 81mg po daglig x 7 dager eller slutten av sykehusinnleggelsen.
Første dose administrert på dag 1 etter operasjon.
Aspirin 325mg po daglig x 7 dager eller slutten av sykehusinnleggelsen.
Første dose administrert på dag 1 etter operasjon.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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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
Tidsramme: Postoperative Day 4
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Postoperative Day 4
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Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Arachidonic Acid Induced Light Transmission Aggregometry (LTA): Aggregering vil bli uttrykt som den maksimale prosentvise endringen i lystransmittans fra baseline, med blodplatefattig plasma brukt som referanse.
Tidsramme: Postoperativ dag 4
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Postoperativ dag 4
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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).
Tidsramme: Postoperative Day 4
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Postoperative Day 4
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DNA genetic analyses for single nucleotide polymorphisms
Tidsramme: A single preoperative blood sample was drawn (on average of 1 week prior to surgery)
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A single preoperative blood sample was drawn (on average of 1 week prior to surgery)
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Samarbeidspartnere og etterforskere
Etterforskere
- Hovedetterforsker: Jeremy Paikin, MD, Cardiology Fellow
- Hovedetterforsker: John Eikelboom, MBBS, Hematologist, PHRI researcher
- Hovedetterforsker: Richard Whitlock, MD, Cardiac Surgeon, PHRI researcher
- Hovedetterforsker: Guillaume Pare, MD, Medical Biochemist, PHRI researcher
- Studiestol: Jack Hirsh, MD, Hematologist, Professor Emeritus, PHRI researcher
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Agenter fra det perifere nervesystemet
- Enzymhemmere
- Analgetika
- Sensoriske systemagenter
- Anti-inflammatoriske midler, ikke-steroide
- Analgetika, ikke-narkotisk
- Anti-inflammatoriske midler
- Antirevmatiske midler
- Fibrinolytiske midler
- Fibrinmodulerende midler
- Blodplateaggregasjonshemmere
- Syklooksygenase-hemmere
- Antipyretika
- Aspirin
Andre studie-ID-numre
- NIF-11271
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