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

NCT ID: NCT01755520

Last Updated: 2018-08-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1893 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-24
• Study Completion Date: 2018-05-19

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.

Conditions

Coronary Artery Disease; Stable Angina; Acute Coronary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ticagrelor

Intervention: Drug: Ticagrelor verum + Aspirin placebo

Group Type: EXPERIMENTAL

Ticagrelor

Intervention Type: DRUG

90mg twice daily dose

Placebo - Aspirin

Intervention Type: DRUG

Placebo

Aspirin

Intervention: Drug: Aspirin verum + Ticagrelor placebo

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

Aspirin 100mg once daily

Placebo - Ticagrelor

Intervention Type: DRUG

Placebo

Interventions

Ticagrelor

90mg twice daily dose

Intervention Type: DRUG

Aspirin

Aspirin 100mg once daily

Intervention Type: DRUG

Placebo - Ticagrelor

Placebo

Intervention Type: DRUG

Placebo - Aspirin

Placebo

Intervention Type: DRUG

Other Intervention Names

Brilique; ASS; Placebo; Placebo

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Deutsches Herzzentrum Muenchen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Heribert Schunkert, MD

Role: STUDY_CHAIR

Deutsches Herzzentrum Munich Germany

Locations

Medizinische Universität Wien

Vienna, , Austria

Klinikum Wels-Grieskirchen

Wels, , Austria

Deutsches Herzzentrum München

Munich, Bavaria, Germany

Herzzentrum Brandenburg in Bernau

Bernau bei Berlin, Brandenburg, Germany

Herz- und Kreislaufzentrum Rothenburg an der Fulda

Rotenburg an der Fulda, Hesse, Germany

Universitätsklinikum Jena

Jena, Thuringia, Germany

Universitätsklinikum Aachen

Aachen, , Germany

Herz- und Gefäßzentrum

Bad Bevensen, , Germany

Kerckhoff-Klinik GmbH

Bad Nauheim, , Germany

Charité Universitätsmedizin Berlin

Berlin, , Germany

Deutsches Herzzentrum Berlin

Berlin, , Germany

Gesundheit Nord gGmbH, Klinikum Links der Weser gGmbH

Bremen, , Germany

Sana Herzzentrum Cottbus GmbH

Cottbus, , Germany

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

Universitätsklinikum Erlangen

Erlangen, , Germany

St. Antonius Hospital

Eschweiler, , Germany

Universitäts-Herzzentrum Freiburg / Bad Krozingen

Freiburg im Breisgau, , Germany

Universitätsklinikum Gießen

Giessen, , Germany

Universitätsmedizin Göttingen

Göttingen, , Germany

Asklepios Klinik St.Georg

Hamburg, , Germany

Universitäres Herzzentrum Hamburg GmbH

Hamburg, , Germany

Universitätsklinikum Schleswig-Holstein, Campus Kiel

Kiel, , Germany

Herzzentrum Leipzig GmbH

Leipzig, , Germany

Klinikum Ludwigshafen

Ludwigshafen, , Germany

Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Lübeck, , Germany

Kliniken Maria Hilf GmbH

Mönchengladbach, , Germany

Klinikum Nürnberg Süd

Nuremberg, , Germany

Krankenhaus der Barmherzigen Brüder Trier

Trier, , Germany

Schweizer Herz- und Gefässchirurgie

Bern, , Switzerland

Countries

Austria; Germany; Switzerland

References

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.

Reference Type: DERIVED

PMID: 31750899 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31145798 (View on PubMed)

Other Identifiers

2012-003630-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GE IDE No. D00112

Identifier Type: -

Identifier Source: org_study_id