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

Coronary Artery Disease Clinical Trial

— TiCAB  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01755520
• Other study ID #: GE IDE No. D00112
• Secondary ID: 2012-003630-16
• Status: Terminated
• Phase: Phase 3
• Start date: April 24, 2013
• Est. completion date: May 19, 2018

Study information

• Verified date: August 2018
• Source: Deutsches Herzzentrum Muenchen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1893
• Est. completion date: May 19, 2018
• Est. primary completion date: May 19, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Angina, Stable
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia
• Stable Angina

Intervention

Drug:
• Ticagrelor
90mg twice daily dose
• Aspirin
Aspirin 100mg once daily
• Placebo - Ticagrelor
Placebo
• Placebo - Aspirin
Placebo

Locations

Country	Name	City	State
Austria	Medizinische Universität Wien	Vienna
Austria	Klinikum Wels-Grieskirchen	Wels
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	Herzzentrum Brandenburg in Bernau	Bernau bei Berlin	Brandenburg
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
Germany	Universitätsklinikum Gießen	Gießen
Germany	Universitätsmedizin Göttingen	Göttingen
Germany	Asklepios Klinik St.Georg	Hamburg
Germany	Universitäres Herzzentrum Hamburg GmbH	Hamburg
Germany	Universitätsklinikum Jena	Jena	Thuringia
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Kiel
Germany	Herzzentrum Leipzig GmbH	Leipzig
Germany	Universitätsklinikum Schleswig-Holstein, Campus Lübeck	Lübeck
Germany	Klinikum Ludwigshafen	Ludwigshafen
Germany	Kliniken Maria Hilf GmbH	Mönchengladbach
Germany	Deutsches Herzzentrum München	Munich	Bavaria
Germany	Klinikum Nürnberg Süd	Nürnberg
Germany	Herz- und Kreislaufzentrum Rothenburg an der Fulda	Rotenburg An Der Fulda	Hesse
Germany	Krankenhaus der Barmherzigen Brüder Trier	Trier
Switzerland	Schweizer Herz- und Gefässchirurgie	Bern

Sponsors (2)

Lead Sponsor	Collaborator
Deutsches Herzzentrum Muenchen	AstraZeneca

Countries where clinical trial is conducted

Austria,  Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MACCE	Composite of cardiovascular death, myocardial infarction, target vessel revascularization, and stroke	at 12 months after coronary artery bypass surgery
Secondary	Cardiovascular death		at 12 months after coronary artery bypass surgery
Secondary	Major bleeding events	Incidence of major bleeding events	within 12 months after coronary arerty bypass surgery
Secondary	All cause death	All cause death	at 12 months after coronary artery bypass surgery
Secondary	Myocardial Infarction		at 12 months after coronary artery bypass surgery
Secondary	Target Lesion Revascularization		at 12 months after coronary artery bypass surgery
Secondary	Stroke		at 12 months after coronary artery bypass surgery