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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. (see Contacts and Locations)
Verified October 2014 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: October 23, 2014
Last verified: October 2014
  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 Disease
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:


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: 3850
Study Start Date: April 2013
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (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 labeling 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, Ticagrelor monotherapy (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 (<50%)

Exclusion Criteria:

  1. Indication for oral anticoagulation therapy (i.e. AF) at the time of randomization
  2. Cardiogenic shock, haemodynamic instability
  3. Indication for dual antiplatelet therapy post operatively
  4. Need for concomitant non-coronary surgery (e.g. valve replacement)
  5. Contraindication for ASA or Ticagrelor use (i.e. known allergy)
  6. History of bleeding diathesis within three months prior presentation
  7. History of significant GI bleed within 6 months prior presentation
  8. History of intra cranial hemorrhage
  9. History of moderate to severe liver impairment
  10. Patient requires dialysis
  11. Patient with an increased risk of bradycardic events (e.g. patients without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree AV block or bradycardic-related syncope)
  12. Known, clinically important thrombocytopenia (i.e. <100.000/µl)
  13. Known, clinically important anaemia (i.e. <10mg/dl)
  14. Participation in another investigational drug or device study in the last 30 days
  15. Pregnancy or lactation (for premenopausal women 2 methods of reliable contraception, one of which must be barrier method, are required)
  16. 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, atazanavir, over 1 litre daily of grapefruit juice.
    • Substrates with narrow therapeutic index: cyclosporine, quinidine.
    • Strong inducers: rifampin/rifampicin, phenytoin, carbamazepine.
  17. Any other severe comorbidity such as active cancer
  18. Life expectancy less than 12 months that may result in protocol non-compliance or a risk for being lost to follow-up
  19. Indication for major surgery (e.g. cancer treatment, carotid surgery, cerebral surgery, major vascular surgery)
  20. Previous enrollment or randomization of treatment in the present study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Austria
Medizinische Universität Wien Recruiting
Vienna, Austria, 1090
Contact: Sigrid Sandner, MD    +43-140400 ext 6969    sigrid.sandner@meduniwien.ac.at   
Principal Investigator: Sigird Sandner, MD         
Klinikum Wels-Grieskirchen Not yet recruiting
Wels, Austria, 4600
Contact: Florian Huber, MD    0043 7242 415-2711    florian.huber@klinikum-wegr.at   
Principal Investigator: Florian Huber, MD         
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         
Universitätsklinikum Aachen Recruiting
Aachen, Germany, 52074
Contact: Rüdiger Autschbach, MD    +49-241-80 ext 89221    rautschbach@ukaachen.de   
Principal Investigator: Rüdiger Autschbach, MD         
Herz- und Gefäßzentrum Not yet recruiting
Bad Bevensen, Germany, 29549
Contact: Gerhard Wimmer-Greinecker, MD    05821 82-1772    g.wimmer-greinecker@hgz-bb.de   
Principal Investigator: Gerhard Wimmer-Greinecker, MD         
Kerckhoff-Klinik GmbH Not yet recruiting
Bad Nauheim, Germany, 61231
Contact: Jörg Kempfert, MD    06032/996-2502    j.kempfert@kerckhoff-klinik.de   
Contact: Tibor Ziegelhöffer, MD    06032/996-2502    t.ziegelhoeffer@kerckhoff-klinik.de   
Principal Investigator: Jörg Kempfert, MD         
Deutsches Herzzentrum Berlin Not yet recruiting
Berlin, Germany, 13353
Contact: Roland Hetzer, MD    030 4593-2000    hetzer@dhzb.de   
Principal Investigator: Roland Hetzer, MD         
Gesundheit Nord gGmbH, Klinikum Links der Weser gGmbH Recruiting
Bremen, Germany, 28277
Contact: Rainer Hambrecht, MD    +49-421-879 ext 1430    rainer.hambrecht@klinikum-bremen-LdW.de   
Principal Investigator: Rainer Hambrecht, MD         
Sana Herzzentrum Cottbus GmbH Not yet recruiting
Cottbus, Germany, 03048
Contact: Jürgen Krülls-München, MD    +49-355-46 ext 2576    1.med.klinik@ctk.de   
Principal Investigator: Jürgen Krülls-Münch, MD         
Universitätsklinikum Düsseldorf Not yet recruiting
Düsseldorf, Germany, 40225
Contact: Malte Kelm, MD    +49-211-811 ext 8801    malte.kelm@med.uni-duesseldorf.de   
Principal Investigator: Malte Kelm, MD         
Universitätsklinikum Erlangen Not yet recruiting
Erlangen, Germany, 91054
Contact: Christian Schlundt, MD    +49-9131-853 ext 5000    christian.schlundt@uk-erlangen.de   
Principal Investigator: Christian Schlundt, MD         
St. Antonius Hospital Not yet recruiting
Eschweiler, Germany, 52249
Contact: Uwe Janssens, MD    02403 76 -1227    uwe.janssens@sah-eschweiler.de   
Principal Investigator: Uwe Janssens, MD         
Universitäts-Herzzentrum Freiburg / Bad Krozingen Recruiting
Freiburg, Germany, 79106
Contact: Matthias Siepe, MD    +49-761-2702 ext 4010    matthias.siepe@universitaets-herzzentrum.de   
Principal Investigator: Matthias Siepe, MD         
Universitätsklinikum Gießen Recruiting
Gießen, Germany, 35392
Contact: Andreas Böning, MD    +49-641-985 ext 44300    andreas.boening@chiru.med.uni-giessen.de   
Principal Investigator: Andreas Böning, MD         
Universitätsmedizin Göttingen Recruiting
Göttingen, Germany, 37075
Contact: Bernd Danner, MD    +49-551-39 ext 6061    bernd.danner@med.uni-goettingen.de   
Principal Investigator: Bernd Danner, MD         
Asklepios Klinik St.Georg Not yet recruiting
Hamburg, Germany, 20099
Contact: Martin Oberhoffer, MD    040 18 18 85 4150    m.oberhoffer@asklepios.com   
Principal Investigator: Martin Oberhoffer, MD         
Universitätsklinikum Schleswig-Holstein, Campus Kiel Recruiting
Kiel, Germany, 24105
Contact: Tim Attmann, MD    +49-431-597 ext 4465    tim.attmann@uksh-kiel.de   
Principal Investigator: Tim Attmann, MD         
Herzzentrum Leipzig GmbH Not yet recruiting
Leipzig, Germany, 04289
Contact: Martin Misfeld, MD         
Principal Investigator: Martin Misfeld, MD         
Klinikum Ludwigshafen Recruiting
Ludwigshafen, Germany, 67063
Contact: Uwe Zeymer, MD    +49-621-503 ext 2941    zeymeru@klilu.de   
Principal Investigator: Uwe Zeymer, MD         
Universitätsklinikum Schleswig-Holstein, Campus Lübeck Recruiting
Lübeck, Germany, 23538
Contact: Michael Reppel, MD    +49-451-500 ext 2500    michael.reppel@uk-sh.de   
Principal Investigator: Michael Reppel, MD         
Kliniken Maria Hilf GmbH Recruiting
Mönchengladbach, Germany, 41063
Contact: Jürgen vom Dahl, MD    02161-892 2231    juergen.vomdahl@mariahilf.de   
Principal Investigator: Jürgen vom Dahl, MD         
Klinikum Nürnberg Süd Not yet recruiting
Nürnberg, Germany, 90419
Contact: Theodor Fischlein, MD    0911 398-5441    theodor.fischlein@klinikum-nuernberg.de   
Principal Investigator: Theodor Fischlein, MD         
Herz- und Kreislaufzentrum Rotenburg a .d. Fulda Not yet recruiting
Rotenburg a .d. Fulda, Germany, 36199
Contact: Ardawan Rastan, MD    06623 885859    a.rastan@hkz-rotenburg.de   
Principal Investigator: Ardawan Rastan, MD         
Krankenhaus der Barmherzigen Brüder Trier Not yet recruiting
Trier, Germany, 54292
Contact: Ivar Friedrich, MD    +49-651-208 ext 2751    i.friedrich@bk-trier.de   
Principal Investigator: Ivar Friedrich, 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: October 23, 2014
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:
Acute Coronary Syndrome
Angina, Stable
Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Angina Pectoris
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Chest Pain
Heart Diseases
Pain
Signs and Symptoms
Vascular Diseases
Aspirin
Ticagrelor
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antipyretics
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on November 20, 2014