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The Effect Of Ticagrelor On Saphenous Vein Graft Patency In Patients Undergoing Coronary Artery Bypass Grafting Surgery (POPular CABG)

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ClinicalTrials.gov Identifier: NCT02352402
Recruitment Status : Active, not recruiting
First Posted : February 2, 2015
Last Update Posted : April 27, 2020
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
J.M. ten Berg, St. Antonius Hospital

Brief Summary:
In the POPular CABG study we investigate if the addition of ticagrelor, a drug that inhibits blood platelets from clotting, to treatment with aspirin will reduce the rate of saphenous vein graft occlusion as assessed with coronary computed tomography angiography at 1 year after coronary artery bypass grafting surgery.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Stable Angina Acute Coronary Syndrome Drug: Ticagrelor Drug: Placebo Phase 3

Detailed Description:

Rationale: Acetylsalicylic acid (ASA) is used to prevent the occlusion of grafts placed during coronary artery bypass grafting surgery (CABG) and to reduce the incidence of atherothrombotic events during follow-up. Graft occlusion occurs predominantly in saphenous vein grafts (SVGs) and can result in symptoms of chest pain, myocardial infarction (MI) and even death. The anti-thrombotic effect of ASA is a result of the inhibition of the generation of thromboxane A2 (TXA2) in blood platelets. Despite ASA therapy, 6.8% to 26% of SVGs occlude in the first year after CABG, mainly due to thrombus formation. This might be due to the fact that ASA is not equally effective in all patients, indicated by a substantial amount of patients that still generate TXA2 and show activated platelets, despite adequate ASA use. We hypothesize that more potent platelet inhibition by the addition of ticagrelor to standard ASA therapy could decrease the rate of SVG occlusion.

Main objective: To investigate whether a combination of ticagrelor 90mg twice daily and ASA 80mg once daily is superior to ASA 80mg once daily alone in the prevention of SVG occlusion in patients who underwent CABG with use of one or more SVGs, as assessed with coronary computed tomography angiography (CCTA) at 1 year after randomization.

Study design: Randomized, double-blind, placebo-controlled, multicenter trial. Number of patients: Approximately 500 patients will be randomized.

Study population: Patients undergoing CABG with one or more SVGs, CABG being an isolated procedure or part of combined surgery.

Informed consent procedure, screening and sample size: We will screen patients and obtain informed consent before CABG. After CABG patients who gave informed consent are screened again to check if the patient fulfills the inclusion criteria and does not have any exclusion criteria. A total of 500 patients will receive randomized study medication after CABG.

Intervention: Patients will be randomly assigned to treatment with 90mg of ticagrelor or a matching placebo twice daily in addition to standard treatment with ASA for the duration of 1 year. Patients will be prescribed 80mg of ASA once daily according to routine clinical practice. Graft patency will be assessed with CCTA 1 year after randomization. If the patient consents to participate in the substudies, platelet function tests will be performed before surgery and 3 days and 1 year after randomization. Thirty day and one-year follow-up of clinical events will be obtained for all patients by screening the (electronic) patient file, telephonic interviews, study site visits and possibly with questionnaires.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 487 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Trial Investigating The Effect Of Ticagrelor On Saphenous Vein Graft Patency In Patients Undergoing Coronary Artery Bypass Grafting Surgery (The POPular CABG Study)
Study Start Date : March 2015
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Ticagrelor

Arm Intervention/treatment
Experimental: Ticagrelor
Ticagrelor 90mg twice daily for 1 year on top of ASA
Drug: Ticagrelor
Other Names:
  • Brilique
  • Brillinta

Placebo Comparator: Placebo
Placebo matching ticagrelor 90mg twice daily on top of ASA
Drug: Placebo



Primary Outcome Measures :
  1. Saphenous vein graft occlusion [ Time Frame: 1 year after coronary artery bypass grafting ]
    As assessed with coronary computed tomography angiography or clinically indicated coronary angiography


Secondary Outcome Measures :
  1. Saphenous vein graft failure [ Time Frame: 1 year after coronary artery bypass grafting ]
    Composite of saphenous vein graft occlusion as assessed with coronary computed tomography angiography or clinically indicated coronary angiography, saphenous vein graft revascularization, myocardial infarction in the myocardial territory supplied by a saphenous vein graft or sudden death

  2. Significant saphenous vein graft stenosis [ Time Frame: 1 year after coronary artery bypass grafting ]
    As assessed with coronary computed tomography angiography or clinically indicated coronary angiography

  3. BARC minor (type 1 or 2) and major (type 3, 4 or 5) bleeding [ Time Frame: 30 days after coronary artery bypass grafting ]
    Bleeding Academic Research Consortium bleeding criteria

  4. BARC minor (type 1 or 2) and major (type 3, 4 or 5) bleeding [ Time Frame: 1 year after coronary artery bypass grafting ]
    Bleeding Academic Research Consortium bleeding criteria

  5. TIMI minor and major bleeding [ Time Frame: 30 days after coronary artery bypass grafting ]
    Thrombolysis in Myocardial Infarction bleeding criteria

  6. TIMI minor and major bleeding [ Time Frame: 1 year after coronary artery bypass grafting ]
    Thrombolysis in Myocardial Infarction bleeding criteria

  7. High platelet reactivity [ Time Frame: Within 72h before coronary artery bypass grafting ]
    As assessed with platelet function tests.

  8. High platelet reactivity [ Time Frame: 3 days after coronary artery bypass grafting ]
    As assessed with platelet function tests.

  9. High platelet reactivity [ Time Frame: 1 year after coronary artery bypass grafting ]
    As assessed with platelet function tests.

  10. Level of GDF-15 [ Time Frame: Within 72h before coronary artery bypass grafting ]
    Growth differentiation factor 15 level

  11. Level of GDF-15 [ Time Frame: 3 days after coronary artery bypass grafting ]
    Growth differentiation factor 15 level

  12. Level of GDF-15 [ Time Frame: 1 year after coronary artery bypass grafting ]
    Growth differentiation factor 15 level

  13. Arterial graft occlusion [ Time Frame: 1 year after coronary artery bypass grafting ]
    As assessed with coronary computed tomography angiography or clinically indicated coronary angiography

  14. All graft occlusion [ Time Frame: 1 year after coronary artery bypass grafting ]
    As assessed with coronary computed tomography angiography or clinically indicated coronary angiography

  15. Significant arterial graft stenosis [ Time Frame: 1 year after coronary artery bypass grafting ]
    As assessed with coronary computed tomography angiography or clinically indicated coronary angiography



Information from the National Library of Medicine

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Ages Eligible for Study:   22 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • More than 21 years of age
  • Planned coronary artery bypass grafting (CABG) with the use of 1 or more saphenous vein grafts, CABG being an isolated procedure or part of a combined aortic valce replacement surgery with bioprothesis.

Exclusion Criteria:

  • Unable to give informed consent or a life expectancy of less than 1 year
  • Concomitant valve, aorta or rhythm surgery during the same session, (excluding aortic bioprothesis)
  • Inability to undergo coronary computed tomography angiography, in the investigator's opinion, for instance due to severe claustrophobia or contrast allergy
  • Use of oral anticoagulants (acenocoumarol, phenprocoumon, dabigatran, rivaroxaban, etc) and a contraindication for discontinuation of this medication or the expectation that the patient will have an indication for the use of these drugs after surgery
  • Placement of a drug-eluting stent in a coronary or cerebral artery within 6 months of CABG or placement of a bare-metal stent in a coronary or cerebral artery within 1 month of CABG
  • Use of antiplatelet drugs other than aspirin (clopidogrel, prasugrel, ticagrelor, dipyridamol, etc.) and a contraindication for discontinuation of this medication after CABG, according to the treating physician or the investigator
  • Women who are known to be pregnant, who have given birth within the past 90 days or who are breastfeeding
  • Pre-menopausal women without adequate contraception
  • Severe renal function impairment requiring dialysis
  • Moderate or severe hepatic impairment
  • Active malignancy with increase in bleeding risk, in the investigator's opinion
  • Use of strong inhibitors of CYP3A4 (e.g. ketaconazole, clarithromycin, nefazodone, ritonavir, atazanavir)
  • Clinically significant out of range values for platelet count or haemoglobin at screening, in the investigator's opinion
  • Contraindication for the use of ticagrelor or aspirin (i.e. history of intracranial bleeding, high bleeding risk, previous allergic reaction), in the investigator's opinion
  • Previous inclusion in this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02352402


Locations
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Netherlands
St Antonius Hospital
Nieuwegein, Utrecht, Netherlands, 3435CM
Catharina Ziekenhuis
Eindhoven, Netherlands, 5623 EJ
Medisch Spectrum Twente
Enschede, Netherlands
Universitair Medisch Centrum Groningen
Groningen, Netherlands
Radboud UMC
Nijmegen, Netherlands
Erasmus Erasmus UMC
Rotterdam, Netherlands
Sponsors and Collaborators
J.M. ten Berg
AstraZeneca
Investigators
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Study Chair: Jurriën M ten Berg, MD, PhD ST. Antonius hospital Nieuwegein
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: J.M. ten Berg, MD, PhD, FESC, FACC, St. Antonius Hospital
ClinicalTrials.gov Identifier: NCT02352402    
Other Study ID Numbers: POPCABG
2014-002142-50 ( EudraCT Number )
First Posted: February 2, 2015    Key Record Dates
Last Update Posted: April 27, 2020
Last Verified: April 2020
Keywords provided by J.M. ten Berg, St. Antonius Hospital:
CABG
Ticagrelor
Graft
Patency
Additional relevant MeSH terms:
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Coronary Artery Disease
Acute Coronary Syndrome
Angina, Stable
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Angina Pectoris
Chest Pain
Pain
Neurologic Manifestations
Signs and Symptoms
Ticagrelor
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs