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.
Aperçu de l'étude
Statut
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
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Ontario
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Hamilton, Ontario, Canada, L8L2X2
- Hamilton General Hospital
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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)
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Double
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Comparateur actif: Aspirin 81mg daily
Patients will receive 81mg daily during the postoperative period.
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Aspirine 81 mg po par jour x 7 jours ou fin d'hospitalisation.
Première dose administrée le jour postopératoire 1.
Aspirine 325 mg po par jour x 7 jours ou fin d'hospitalisation.
Première dose administrée le jour postopératoire 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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Comparateur actif: Aspirine 325 mg par jour
Les patients recevront 325 mg par jour pendant la période postopératoire, jusqu'au jour 7 postopératoire ou à la fin de l'hospitalisation.
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Aspirine 81 mg po par jour x 7 jours ou fin d'hospitalisation.
Première dose administrée le jour postopératoire 1.
Aspirine 325 mg po par jour x 7 jours ou fin d'hospitalisation.
Première dose administrée le jour postopératoire 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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Expérimental: 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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Aspirine 81 mg po par jour x 7 jours ou fin d'hospitalisation.
Première dose administrée le jour postopératoire 1.
Aspirine 325 mg po par jour x 7 jours ou fin d'hospitalisation.
Première dose administrée le jour postopératoire 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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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
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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
Délai: Postoperative Day 4
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Postoperative Day 4
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Mesures de résultats secondaires
Mesure des résultats |
Délai |
|---|---|
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Agrégométrie de transmission de la lumière induite par l'acide arachidonique (LTA) : L'agrégation sera exprimée comme le pourcentage maximal de variation de la transmission de la lumière par rapport à la ligne de base, le plasma pauvre en plaquettes étant utilisé comme référence.
Délai: Jour postopératoire 4
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Jour postopératoire 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).
Délai: Postoperative Day 4
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Postoperative Day 4
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DNA genetic analyses for single nucleotide polymorphisms
Délai: 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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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Jeremy Paikin, MD, Cardiology Fellow
- Chercheur principal: John Eikelboom, MBBS, Hematologist, PHRI researcher
- Chercheur principal: Richard Whitlock, MD, Cardiac Surgeon, PHRI researcher
- Chercheur principal: Guillaume Pare, MD, Medical Biochemist, PHRI researcher
- Chaise d'étude: Jack Hirsh, MD, Hematologist, Professor Emeritus, PHRI researcher
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents du système nerveux périphérique
- Inhibiteurs d'enzymes
- Analgésiques
- Agents du système sensoriel
- Agents anti-inflammatoires non stéroïdiens
- Analgésiques, non narcotiques
- Agents anti-inflammatoires
- Agents antirhumatismaux
- Agents fibrinolytiques
- Agents modulateurs de fibrine
- Inhibiteurs de l'agrégation plaquettaire
- Inhibiteurs de la cyclooxygénase
- Antipyrétiques
- Aspirine
Autres numéros d'identification d'étude
- NIF-11271
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Essais cliniques sur Aspirine
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Montreal Heart InstituteInstitut de Recherches Cliniques de MontrealRecrutementDiabète sucré, Type 2 | Diabète de type 2 | Agrégation plaquettaire | Aspirine | Inhibiteurs de l'agrégation plaquettaireCanada