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Study Comparing Ticagrelor With Aspirin for Prevention of Vascular Events in Patients Undergoing CABG (TiCAB)

This study is currently recruiting participants.
Verified May 2013 by Deutsches Herzzentrum Muenchen
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Deutsches Herzzentrum Muenchen
ClinicalTrials.gov Identifier:
NCT01755520
First received: December 19, 2012
Last updated: May 15, 2013
Last verified: May 2013
History of Changes
  Purpose

This study (TiCAB) is designed as a pivotal efficacy and safety study of Ticagrelor in patients undergoing coronary artery bypass operation. It is designed for the prevention of fatal and non-fatal cardiovascular events in this patient population, a significant, yet unmet medical need.


Condition Intervention Phase
Coronary Artery Desease,
Stable Angina,
Acute Coronary Syndrome
 Drug: Ticagrelor
Drug: Aspirin
Drug: Placebo - Ticagrelor
Drug: Placebo - Aspirin
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Parallel Group, Double-Blind Study of Ticagrelor Compared With Aspirin for Prevention of Vascular Events in Patients Undergoing Coronary Artery Bypass Graft Operation TiCAB- Ticagrelor in CABG

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Deutsches Herzzentrum Muenchen:

Primary Outcome Measures:
  • MACCE [ Time Frame: at 12 months after coronary artery bypass surgery ] [ Designated as safety issue: No ]
    Composite of cardiovascular death, myocardial infarction, target vessel revascularization, and stroke


Secondary Outcome Measures:
  • Cardiovascular death [ Time Frame: at 12 months after coronary artery bypass surgery ] [ Designated as safety issue: No ]
  • Major bleeding events [ Time Frame: within 12 months after coronary arerty bypass surgery ] [ Designated as safety issue: Yes ]
    Incidence of major bleeding events

  • All cause death [ Time Frame: at 12 months after coronary artery bypass surgery ] [ Designated as safety issue: No ]
    All cause death

  • Myocardial Infarction [ Time Frame: at 12 months after coronary artery bypass surgery ] [ Designated as safety issue: No ]
  • Target Lesion Revascularization [ Time Frame: at 12 months after coronary artery bypass surgery ] [ Designated as safety issue: No ]
  • Stroke [ Time Frame: at 12 months after coronary artery bypass surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 4008
Study Start Date: April 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ticagrelor
Intervention: Drug: Ticagrelor verum + Aspirin placebo
 Drug: Ticagrelor
90mg twice daily dose
Other Name: Brilique
Drug: Placebo - Aspirin
Placebo
Other Name: Placebo
Active Comparator: Aspirin
Intervention: Drug: Aspirin verum + Ticagrelor placebo
 Drug: Aspirin
Aspirin 100mg once daily
Other Name: ASS
Drug: Placebo - Ticagrelor
Placebo
Other Name: Placebo

Detailed Description:

For stable patients who underwent coronary bypass operation, Aspirin alone currently represents the gold standard of antiplatelet treatment. A few smaller studies using a combination therapy of antiplatelet drugs including Aspirin and Clopidogrel have shown conflicting results. Albeit a number of cardiac surgeons prefer dual antiplatelet therapy with Aspirin and Clopidogrel, Aspirin monotherapy is currently the only guideline recommended therapy after CABG.

A sub-analysis of PLATO trial comprising more than 1200 ACS patients who were not considered to be appropriately suited for PCI and therefore subjected to CABG operation demonstrated an impressive reduction in mortality in those patients treated with Ticagrelor and Aspirin as compared to Clopidogrel and Aspirin. The labelling of Ticagrelor says that the drug should be paused 7 days prior to surgery. However, a further analysis of this substudy revealed that the largest benefit in the Ticagrelor + Aspirin group as compared to the Clopidogrel + Aspirin group was found in those who stopped study medication at about 48 - 72 hours prior to surgery. There have been pharmacological studies that showed that Ticagrelor may precondition the heart for the trauma of surgery via adenosine mediated effects. Thus, the enormous benefit in the Ticagrelor arm of the PLATO study may be secondary to a pleiotropic action. There was no indication of an accelerated bleeding risk in this study and pharmacological studies document that platelet function should be largely restored of a pause of 48 - 72 hours, such that this duration may allow the optimal preparation for CABG surgery.

Based on the unmet clinical need regarding optimal antiplatelet therapy after CABG, the results of the PLATO CABG substudy and the observation that Ticagrelor benefits increase with decreasing Aspirin doses, Ticagrelormonotherapy (2x 90mg/day) appears to offer the best balance of safety with anticipated improved efficacy over Aspirin alone. However, there are no data available to support this hypothesis.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients 18 years of age or older
  2. Informed, written consent by the patient

  3. Indication for CABG surgery:

    • coronary three vessel disease, or
    • left main stenosis, or
    • two vessel disease with impaired left ventricular function

Exclusion Criteria:

  1. Indication for oral anticoagulation therapy (i.e. AF) at the time of randomization
  2. Cardiogenic shock, haemodynamic instability
  3. Acute myocardial infarction at presentation (STEMI)
  4. Need for urgent revascularization within 5 days from presentation
  5. Single or two vessel disease with normal LV function (≥ 50%)
  6. Need for concomitant non-coronary surgery (e.g. valve replacement)
  7. Contraindication for Aspirin or Ticagrelor use (i.e. known allergy)
  8. History of bleeding diathesis within three months prior presentation, significant GI bleed, intra cranial hemorrhage, or liver failure
  9. Patient requires dialysis
  10. Known, clinically important thrombocytopenia (i.e. <100.000/µl)
  11. Known, clinically important anaemia (i.e. <10mg/dl)
  12. Participation in another investigational drug or device study in the last 30 days
  13. Pregnancy or lactation (for premenopausal women 2 methods of reliable contraception, one of which must be barrier method, are required)

  14. Concomitant oral or intravenous therapy (see examples below) with strong CYP3A inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers which cannot be stopped for the course of the study

    • Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir, over 1 litre daily of grapefruit juice.
    • Substrates with narrow therapeutic index: cyclosporine, quinidine.
    • Strong inducers: rifampin/rifampicin, phenytoin, carbamazepine.
  15. Any other condition such as active cancer
  16. Life expectancy less than 12 months that may result in protocol non-compliance or a risk for being lost to follow-up
  17. Indication for major surgery (e.g. cancer treatment, carotid surgery, cerebral surgery, major vascular surgery)
  18. Previous enrolment or randomization of treatment in the present study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01755520

Contacts
Contact: Heribert Schunkert, MD 00498912184073 schunkert@dhm.mhn.de
Contact: Gisela Schoemig 00498912181547 gschoemig@dhm.mhn.de

Locations
Germany
Deutsches Herzzentrum München Recruiting
Munich, Bavaria, Germany, 80636
Contact: Heribert Schunkert, MD     00498912184073     schunkert@dhm.mhn.de    
Contact: Adnan Kastrati, MD     00498912184578     kastrati@dhm.mhn.de    
Principal Investigator: Heribert Schunkert, MD            
Sponsors and Collaborators
Deutsches Herzzentrum Muenchen
AstraZeneca
Investigators
Principal Investigator: Heribert Schunkert, MD Deutsches Herzzentrum Munich Germany
  More Information

No publications provided

Responsible Party: Deutsches Herzzentrum Muenchen
ClinicalTrials.gov Identifier: NCT01755520     History of Changes
Other Study ID Numbers: GE IDE No. D00112, 2012-003630-16
Study First Received: December 19, 2012
Last Updated: May 15, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Deutsches Herzzentrum Muenchen:
CABG,
CAD,
antiplatelet drug,
Ticagrelor,
Aspirin

Additional relevant MeSH terms:
Platelet Aggregation Inhibitors
Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Aspirin
Ticagrelor
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
 Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics

ClinicalTrials.gov processed this record on May 19, 2013