Clinical trial NCT01755520: Study Comparing Ticagrelor With Aspirin for Prevention of Vascular Events in Patients Undergoing CABG
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Coronary Artery Disease
Stable Angina
Acute Coronary Syndrome
Keywords: CABG
CAD
antiplatelet drug
Ticagrelor
Aspirin
Lead sponsor: Deutsches Herzzentrum Muenchen
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2012-12-24
Enrollment: 1893
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study ist to test the hypothesis that ticagrelor is superior to Aspirin (ASA) fort he prevention of major cardio- and cerebrovascular events (MACCE) in patients undergoing artery bypass operation.

The primary efficiacy MACCE-endpoint is the composite of cardiovascular death, myocardial infarction, recurent revascularisation, and stroke at twelve month after coronary artery bypass operation.

Detailed description: For stable patients who underwent coronary bypass operation, Aspirin alone currently represents the gold standard of antiplatelet treatment.

The CABG substudy of the PLATO-trial (http://www.nejm.org/doi/full/10.1056/NEJMoa0904327) comprising more than 1200 patients has convincingly shown a high significant reduction of cardiovascular and all-cause mortality for patients recieving Aspirin and Ticagrelor as compared to those subjects randomized to Aspirin plus Clopidogrel. Moreover the results of the PLATO CABG substudy showed that benefits of Ticagrelor increase with decreasing Aspirin doses. Therefore Ticagrelor monotherapy (2x 90mg/day) appears to offer the best balance of safety with anticipated improved efficacy over Aspirin (1x 100mg/day) alone, but until now there are no further data available to support this hypothesis.

Hence this study (TiCAB) is assigned as a pivotal efficacy and safety study of Ticagrelor in patients undergoing coronary artery bypass operation and to test the hypothesis that ticagrelor is superior to Aspirin for the prevention of major cardio- and cerebrovascular events (MACCE) in this patient population.

The TiCAB trial is designed as a randomized, double-blind, double-dummy, parallel group, phase III, multicenter study, comparing the efficacy and safety of Ticagrelor 90mg administered twice daily with Aspirin 100mg once daily, for the prevention of MACCE within the first year after CABG operation.

Eligibility 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. Cardiogenic shock, haemodynamic instability
2. Indication for oral anticoagulation or dual antiplatelet therapy that can not be stopped after CABG
3. Need for concomitant non-coronary surgery (e.g. valve replacement)
4. Intolerance of or Allergy to Ticagrelor or ASA or any of their ingredients
5. History of bleeding diathesis within three months prior presentation
6. History of significant gastrointestinal bleeding within six months prior presentation
7. History of intracranial hemorrhage
8. History of moderate to severe liver impairment (Child Pugh B or C)
9. Chronic renal insufficiency requiring dialysis
10. 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)
11. Known, clinically important thrombocytopenia (i.e. \<100.000/µl)
12. Known, clinically important anaemia (i.e. \<10mg/dl)
13. Participation in another investigational drug or device study in the last 30 days
14. Pregnancy or lactation (for premenopausal women 2 methods of reliable contraception, one of which must be barrier method, are required); in women with childbearing potential a pregnancy test is mandatory
15. 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.
16. Life expectancy less than 12 months that may result in protocol non-compliance or a risk for being lost to follow-up, active cancer
17. Indication for major surgery (e.g. cancer treatment, carotid surgery, cerebral surgery, major vascular surgery)
18. Previous enrollment or randomization of treatment in the present study.

Primary outcomes:
measure: MACCE
timeFrame: at 12 months after coronary artery bypass surgery
Secondary outcomes:
measure: Cardiovascular death
timeFrame: at 12 months after coronary artery bypass surgery
measure: Major bleeding events
timeFrame: within 12 months after coronary arerty bypass surgery
measure: All cause death
timeFrame: at 12 months after coronary artery bypass surgery
measure: Myocardial Infarction
timeFrame: at 12 months after coronary artery bypass surgery
measure: Target Lesion Revascularization
timeFrame: at 12 months after coronary artery bypass surgery
measure: Stroke
timeFrame: at 12 months after coronary artery bypass surgery
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medizinische Universität Wien
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen
city: Munich
country: Germany
facility: Deutsches Herzzentrum München
state: Bavaria
city: Bernau bei Berlin
country: Germany
facility: Herzzentrum Brandenburg in Bernau
state: Brandenburg
city: Rotenburg An Der Fulda
country: Germany
facility: Herz- und Kreislaufzentrum Rothenburg an der Fulda
state: Hesse
city: Jena
country: Germany
facility: Universitätsklinikum Jena
state: Thuringia
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen
city: Bad Bevensen
country: Germany
facility: Herz- und Gefäßzentrum
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik GmbH
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Berlin
country: Germany
facility: Deutsches Herzzentrum Berlin
city: Bremen
country: Germany
facility: Gesundheit Nord gGmbH, Klinikum Links der Weser gGmbH
city: Cottbus
country: Germany
facility: Sana Herzzentrum Cottbus GmbH
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Eschweiler
country: Germany
facility: St. Antonius Hospital
city: Freiburg
country: Germany
facility: Universitäts-Herzzentrum Freiburg / Bad Krozingen
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
city: Hamburg
country: Germany
facility: Asklepios Klinik St.Georg
city: Hamburg
country: Germany
facility: Universitäres Herzzentrum Hamburg GmbH
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Kiel
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig GmbH
city: Ludwigshafen
country: Germany
facility: Klinikum Ludwigshafen
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Lübeck
city: Mönchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg Süd
city: Trier
country: Germany
facility: Krankenhaus der Barmherzigen Brüder Trier
city: Bern
country: Switzerland
facility: Schweizer Herz- und Gefässchirurgie
Study officials:
affiliation: Deutsches Herzzentrum Munich Germany
name: Heribert Schunkert, MD
role: STUDY_CHAIR
References:
citation: Sandner SE, Schunkert H, Kastrati A, Wiedemann D, Misfeld M, Boning A, Tebbe U, Nowak B, Stritzke J, Laufer G, von Scheidt M; TiCAB Investigators. Ticagrelor monotherapy versus aspirin in patients undergoing multiple arterial or single arterial coronary artery bypass grafting: insights from the TiCAB trial. Eur J Cardiothorac Surg. 2020 Apr 1;57(4):732-739. doi: 10.1093/ejcts/ezz313.
citation: Schunkert H, Boening A, von Scheidt M, Lanig C, Gusmini F, de Waha A, Kuna C, Fach A, Grothusen C, Oberhoffer M, Knosalla C, Walther T, Danner BC, Misfeld M, Zeymer U, Wimmer-Greinecker G, Siepe M, Grubitzsch H, Joost A, Schaefer A, Conradi L, Cremer J, Hamm C, Lange R, Radke PW, Schulz R, Laufer G, Grieshaber P, Pader P, Attmann T, Schmoeckel M, Meyer A, Ziegelhoffer T, Hambrecht R, Kastrati A, Sandner SE. Randomized trial of ticagrelor vs. aspirin in patients after coronary artery bypass grafting: the TiCAB trial. Eur Heart J. 2019 Aug 1;40(29):2432-2440. doi: 10.1093/eurheartj/ehz185.