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

• ClinicalTrials.gov Identifier: NCT01755520
• Recruitment Status: Terminated
• First Posted: December 24, 2012
• Last Update Posted: August 2, 2018
• Sponsor: Deutsches Herzzentrum Muenchen
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Deutsches Herzzentrum Muenchen

Tracking Information

• First Submitted Date: December 19, 2012
• First Posted Date: December 24, 2012
• Last Update Posted Date: August 2, 2018
• Study Start Date: April 24, 2013
• Actual Primary Completion Date: May 19, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 21, 2012)

MACCE [ Time Frame: at 12 months after coronary artery bypass surgery ]

Composite of cardiovascular death, myocardial infarction, target vessel revascularization, and stroke

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 21, 2012)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Coronary Artery Disease
• Stable Angina
• Acute Coronary Syndrome

Intervention

• Drug: Ticagrelor
  90mg twice daily dose
  Other Name: Brilique
• Drug: Aspirin
  Aspirin 100mg once daily
  Other Name: ASS
• Drug: Placebo - Ticagrelor
  Placebo
  Other Name: Placebo
• Drug: Placebo - Aspirin
  Placebo
  Other Name: Placebo

Study Arms

• Experimental: Ticagrelor
  Intervention: Drug: Ticagrelor verum + Aspirin placebo
  Interventions:

  • Drug: Ticagrelor
  • Drug: Placebo - Aspirin
• Active Comparator: Aspirin
  Intervention: Drug: Aspirin verum + Ticagrelor placebo
  Interventions:

  • Drug: Aspirin
  • Drug: Placebo - Ticagrelor

Publications *

• Sandner SE, Schunkert H, Kastrati A, Wiedemann D, Misfeld M, Böning 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, Ziegelhöffer 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: August 1, 2018): 1893
• Original Estimated Enrollment (submitted: December 21, 2012): 4008
• Actual Study Completion Date: May 19, 2018
• Actual Primary Completion Date: May 19, 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Germany, Switzerland

Administrative Information

• NCT Number: NCT01755520
• Other Study ID Numbers: GE IDE No. D00112; 2012-003630-16 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Deutsches Herzzentrum Muenchen
• Study Sponsor: Deutsches Herzzentrum Muenchen
• Collaborators: AstraZeneca

Investigators

• Study Chair: Heribert Schunkert, MD; Deutsches Herzzentrum Munich Germany

• PRS Account: Deutsches Herzzentrum Muenchen
• Verification Date: August 2018