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Multiple Daily Doses Of Aspirin To Overcome Aspirin Hyporesponsiveness Post Cardiac Bypass Surgery (ASACABG)

18. marts 2015 opdateret af: Jeremy Paikin, Hamilton Health Sciences Corporation

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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret 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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

120

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8L2X2
        • Hamilton General Hospital

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

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

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Dobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: Aspirin 81mg daily
Patients will receive 81mg daily during the postoperative period.
Medicin: Aspirin
Aspirin 81mg po dagligt x 7 dage eller slutningen af ​​indlæggelsen. Første dosis administreret på post op dag 1.
Medicin: Aspirin
Aspirin 325mg po dagligt x 7 dage eller slutningen af ​​indlæggelsen. Første dosis administreret på post op dag 1.
Medicin: Aspirin
Aspirin 81mg po four times daily x 7days or end of hospitalization. First dose administered on post op day 1.
Aktiv komparator: Aspirin 325mg dagligt
Patienterne vil modtage 325 mg dagligt i den postoperative periode, indtil dag 7 postop eller slutningen af ​​hospitalsindlæggelsen.
Medicin: Aspirin
Aspirin 81mg po dagligt x 7 dage eller slutningen af ​​indlæggelsen. Første dosis administreret på post op dag 1.
Medicin: Aspirin
Aspirin 325mg po dagligt x 7 dage eller slutningen af ​​indlæggelsen. Første dosis administreret på post op dag 1.
Medicin: Aspirin
Aspirin 81mg po four times daily x 7days or end of hospitalization. First dose administered on post op day 1.
Eksperimentel: Aspirin 81mg four times daily
Patients will receive ASA 81mg four times daily until postoperative day 7 or end of hospitalization
Medicin: Aspirin
Aspirin 81mg po dagligt x 7 dage eller slutningen af ​​indlæggelsen. Første dosis administreret på post op dag 1.
Medicin: Aspirin
Aspirin 325mg po dagligt x 7 dage eller slutningen af ​​indlæggelsen. Første dosis administreret på post op dag 1.
Medicin: Aspirin
Aspirin 81mg po four times daily x 7days or end of hospitalization. First dose administered on post op day 1.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
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
Postoperative Day 4

Sekundære resultatmål

Resultatmål
Tidsramme
Arachidonic Acid Induced Light Transmission Aggregometry (LTA): Aggregation vil blive udtrykt som den maksimale procentvise ændring i lystransmittans fra baseline, med blodpladefattigt plasma brugt som reference.
Tidsramme: Postoperativ dag 4
Postoperativ 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).
Tidsramme: Postoperative Day 4
Postoperative Day 4
DNA genetic analyses for single nucleotide polymorphisms
Tidsramme: 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)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Hamilton Health Sciences Corporation

Efterforskere

  • Ledende efterforsker: Jeremy Paikin, MD, Cardiology Fellow
  • Ledende efterforsker: John Eikelboom, MBBS, Hematologist, PHRI researcher
  • Ledende efterforsker: Richard Whitlock, MD, Cardiac Surgeon, PHRI researcher
  • Ledende efterforsker: Guillaume Pare, MD, Medical Biochemist, PHRI researcher
  • Studiestol: Jack Hirsh, MD, Hematologist, Professor Emeritus, PHRI researcher

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. januar 2012

Primær færdiggørelse (Faktiske)

1. april 2013

Studieafslutning (Faktiske)

1. august 2013

Datoer for studieregistrering

Først indsendt

1. juni 2012

Først indsendt, der opfyldte QC-kriterier

11. juni 2012

Først opslået (Skøn)

13. juni 2012

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

19. marts 2015

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

18. marts 2015

Sidst verificeret

1. marts 2015

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • NIF-11271

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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