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

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

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.

Study Overview

• Status: Terminated
• Conditions: Coronary Artery Disease; Acute Coronary Syndrome; Stable Angina
• Intervention / Treatment: Drug: Ticagrelor; Drug: Placebo - Aspirin; Drug: Aspirin; Drug: Placebo - Ticagrelor

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.

• Study Type: Interventional
• Enrollment (Actual): 1893
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medizinische Universitat Wien
  • Wels, Austria, 4600
    • Klinikum Wels-Grieskirchen
• Germany
  • Aachen, Germany, 52074
    • Universitätsklinikum Aachen
  • Bad Bevensen, Germany, 29549
    • Herz- und Gefäßzentrum
  • Bad Nauheim, Germany, 61231
    • Kerckhoff-Klinik GmbH
  • Berlin, Germany, 13353
    • Deutsches Herzzentrum Berlin
  • Berlin, Germany, 10117
    • Charité Universitätsmedizin Berlin
  • Bremen, Germany, 28277
    • Gesundheit Nord gGmbH, Klinikum Links der Weser gGmbH
  • Cottbus, Germany, 03048
    • Sana Herzzentrum Cottbus GmbH
  • Düsseldorf, Germany, 40225
    • Universitatsklinikum Dusseldorf
  • Erlangen, Germany, 91054
    • Universitatsklinikum Erlangen
  • Eschweiler, Germany, 52249
    • St. Antonius Hospital
  • Freiburg, Germany, 79106
    • Universitäts-Herzzentrum Freiburg / Bad Krozingen
  • Gießen, Germany, 35392
    • Universitätsklinikum Gießen
  • Göttingen, Germany, 37075
    • Universitatsmedizin Gottingen
  • Hamburg, Germany, 20099
    • Asklepios Klinik St.Georg
  • Hamburg, Germany, 20299
    • Universitäres Herzzentrum Hamburg GmbH
  • Kiel, Germany, 24105
    • Universitatsklinikum Schleswig-Holstein, Campus Kiel
  • Leipzig, Germany, 04289
    • Herzzentrum Leipzig GmbH
  • Ludwigshafen, Germany, 67063
    • Klinikum Ludwigshafen
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
  • Mönchengladbach, Germany, 41063
    • Kliniken Maria Hilf GmbH
  • Nürnberg, Germany, 90419
    • Klinikum Nurnberg Sud
  • Trier, Germany, 54292
    • Krankenhaus der Barmherzigen Bruder Trier
  • Bavaria
    • Munich, Bavaria, Germany, 80636
      • Deutsches Herzzentrum München
  • Brandenburg
    • Bernau bei Berlin, Brandenburg, Germany, 16321
      • Herzzentrum Brandenburg in Bernau
  • Hesse
    • Rotenburg An Der Fulda, Hesse, Germany, 36199
      • Herz- und Kreislaufzentrum Rothenburg an der Fulda
  • Thuringia
    • Jena, Thuringia, Germany, 07747
      • Universitatsklinikum Jena
• Switzerland
  • Bern, Switzerland, 3010
    • Schweizer Herz- und Gefässchirurgie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ticagrelor; Intervention: Drug: Ticagrelor verum + Aspirin placebo	Drug: Ticagrelor; 90mg twice daily dose; Other Names: Brilique; Drug: Placebo - Aspirin; Placebo; Other Names: Placebo
Active Comparator: Aspirin; Intervention: Drug: Aspirin verum + Ticagrelor placebo	Drug: Aspirin; Aspirin 100mg once daily; Other Names: ASS; Drug: Placebo - Ticagrelor; Placebo; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACCE	Composite of cardiovascular death, myocardial infarction, target vessel revascularization, and stroke	at 12 months after coronary artery bypass surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular death		at 12 months after coronary artery bypass surgery
Major bleeding events	Incidence of major bleeding events	within 12 months after coronary arerty bypass surgery
All cause death	All cause death	at 12 months after coronary artery bypass surgery
Myocardial Infarction		at 12 months after coronary artery bypass surgery
Target Lesion Revascularization		at 12 months after coronary artery bypass surgery
Stroke		at 12 months after coronary artery bypass surgery

Collaborators and Investigators

• Sponsor: Deutsches Herzzentrum Muenchen
• Collaborators: AstraZeneca
• Investigators: Study Chair: Heribert Schunkert, MD, Deutsches Herzzentrum Munich Germany

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: April 24, 2013
• Primary Completion (Actual): May 19, 2018
• Study Completion (Actual): May 19, 2018

Study Registration Dates

• First Submitted: December 19, 2012
• First Submitted That Met QC Criteria: December 21, 2012
• First Posted (Estimate): December 24, 2012

Study Record Updates

• Last Update Posted (Actual): August 2, 2018
• Last Update Submitted That Met QC Criteria: August 1, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Ticagrelor; Aspirin; CABG; CAD; antiplatelet drug
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Coronary Disease; Chest Pain; Angina Pectoris; Coronary Artery Disease; Acute Coronary Syndrome; Angina, Stable; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Ticagrelor
• Other Study ID Numbers: GE IDE No. D00112; 2012-003630-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided