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.
Panoramica dello studio
Stato
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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Ontario
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Hamilton, Ontario, Canada, L8L2X2
- Hamilton General Hospital
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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)
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Doppio
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Comparatore attivo: Aspirin 81mg daily
Patients will receive 81mg daily during the postoperative period.
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Aspirina 81 mg PO al giorno x 7 giorni o fine del ricovero.
Prima dose somministrata il giorno postoperatorio 1.
Aspirina 325 mg PO al giorno x 7 giorni o fine del ricovero.
Prima dose somministrata il giorno postoperatorio 1.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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Comparatore attivo: Aspirina 325 mg al giorno
I pazienti riceveranno 325 mg al giorno durante il periodo postoperatorio, fino al giorno 7 dopo l'intervento o alla fine del ricovero.
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Aspirina 81 mg PO al giorno x 7 giorni o fine del ricovero.
Prima dose somministrata il giorno postoperatorio 1.
Aspirina 325 mg PO al giorno x 7 giorni o fine del ricovero.
Prima dose somministrata il giorno postoperatorio 1.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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Sperimentale: 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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Aspirina 81 mg PO al giorno x 7 giorni o fine del ricovero.
Prima dose somministrata il giorno postoperatorio 1.
Aspirina 325 mg PO al giorno x 7 giorni o fine del ricovero.
Prima dose somministrata il giorno postoperatorio 1.
Aspirin 81mg po four times daily x 7days or end of hospitalization.
First dose administered on post op day 1.
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
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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
Lasso di tempo: Postoperative Day 4
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Postoperative Day 4
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Misure di risultato secondarie
Misura del risultato |
Lasso di tempo |
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Aggregometria della trasmissione della luce indotta dall'acido arachidonico (LTA): l'aggregazione sarà espressa come variazione percentuale massima della trasmissione della luce rispetto al basale, con plasma povero di piastrine utilizzato come riferimento.
Lasso di tempo: Quarta giornata postoperatoria
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Quarta giornata postoperatoria
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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).
Lasso di tempo: Postoperative Day 4
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Postoperative Day 4
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DNA genetic analyses for single nucleotide polymorphisms
Lasso di tempo: 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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Collaboratori e investigatori
Investigatori
- Investigatore principale: Jeremy Paikin, MD, Cardiology Fellow
- Investigatore principale: John Eikelboom, MBBS, Hematologist, PHRI researcher
- Investigatore principale: Richard Whitlock, MD, Cardiac Surgeon, PHRI researcher
- Investigatore principale: Guillaume Pare, MD, Medical Biochemist, PHRI researcher
- Cattedra di studio: Jack Hirsh, MD, Hematologist, Professor Emeritus, PHRI researcher
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti del sistema nervoso periferico
- Inibitori enzimatici
- Analgesici
- Agenti del sistema sensoriale
- Agenti antinfiammatori, non steroidei
- Analgesici, non narcotici
- Agenti antinfiammatori
- Agenti antireumatici
- Agenti fibrinolitici
- Agenti modulanti la fibrina
- Inibitori dell'aggregazione piastrinica
- Inibitori della ciclossigenasi
- Antipiretici
- Aspirina
Altri numeri di identificazione dello studio
- NIF-11271
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
Prove cliniche su Aspirina
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Galala UniversityCompletatoFegato grasso non alcolico | Diabete di tipo 2Egitto