Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery

Coronary Artery Bypass Clinical Trial

— DACAB  

Official title:

Compare the Efficacy of Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02201771
• Other study ID #: ISSBRIL0211
• Status: Completed
• Phase: Phase 4
• Start date: July 2014
• Est. completion date: January 2017

Study information

• Verified date: August 2019
• Source: Ruijin Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study population will include all patients undergoing elective CABG. Consent and randomization will occur before surgery. Total 500 patients undergoing elective CABG will be randomly assigned into three groups with 1:1:1 ratio(167 patients per group) in this open-label study. All the enrolled patients will stop oral antiplatelet drugs according to local protocol before the surgery. Within the first 24 hours after surgery, study medication should be restarted and continued for 12 months. Arm A will restart oral antiplatelet drugs by giving aspirin 100mg qd, Arm B will also restart oral antiplatelet drugs by giving ticagrelor 90mg bid plus aspirin 100mg qd and Arm C will also restart oral antiplatelet drugs by giving ticagrelor 90mg bid. Treatment will continue for 12 months, at which time patients will undergo a multislice computed tomography angiography to assess vein graft patency.

This study is designed to show the superiority of ticagrelor and ticagrelor plus aspirin as compared with aspirin monotherapy respectively for the 1-year primary efficacy end point of vein graft patency.

Description:

The study is designed to show the superiority of ticagrelor and ticagrelor plus aspirin as compared with aspirin monotherapy respectively for the 1-year primary efficacy end point of vein graft patency. The primary comparison includes two separate parts. One is to demonstrate T+A better than A and the other is T better than A.

One year rate of vein graft patency in the aspirin group is estimated as 80%. The assumed rate of ticagrelor plus aspirin is 90%. With a two-sided alpha level 0.05 and 80% power, 199 grafts to each group are required. On the other hand, if we assume the rate of ticagrelor monotherapy has the 1-year vein graft patency rate of 87%, under the same two-sided 0.05 alpha 441 grafts in each arm will offer 80% power to show the superiority of ticagrelor along for the primary efficacy end point.

Combined the above two assumptions, if the allocation rate is 1:1:1, this study needs to recruit 1,323 grafts in total (441 in each) to achieve the pre-specified power for both the two comparisons (T+A vs. A and T vs. A).

The principle investigator assumes that the average number of the vien grafts in one patient is 2.7-3.0. With this assumption, 500 patients are to be recruited, which will provide us a total of 1350 - 1500 grafts.

According to the above, this study will be a confirmatory clinical trial to the primary endpoint.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 500
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients able to provide written informed consent

• Provision of informed consent prior to any study specific procedures

• Female and male patients aged 18-80 years

• Indication for CABG surgery

Exclusion Criteria:

• Cardiogenic shock, haemodynamic instability

• Need for urgent revascularization within 5 days from presentation

• Single vessel disease

• Two vessel disease with normal left ventricular function (> 50%)

• Need for concomitant other cardiac surgery (e.g. valve replacement)

• Need for dual antiplatelet treatment for the patients undergoing CABG after acute coronary syndrome(ACS)

• Contraindication for aspirin and ticagrelor use(e.g. known allergy)

• History of bleeding diathesis within 3 months prior presentation

• History of significant GI bleed within 1 year prior presentation

• History of peptic ulcer without GI bleeding in past 3 years

• History of intracranial hemorrhage

• History of moderate to severe liver impairment

• Patient requires dialysis

• Patient with an increased risk of bradycardic events (as patients without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree arteriolar-venular block or bradycardic-related syncope)

• Need vitamin K antagonist therapy after bypass surgery eg. persistent atrial fibrillation, mechanical valves

• Known, clinically important thrombocytopenia(i.e. < 100*109/L)

• Known, clinically important anaemia (i.e. <100g/L)

• Participation in another investigational drug or device study in the last 30 days

• Pregnancy or lactation(for premenopausal women 2 methods of reliable contraception, one of which must barrier method, are required)

• Concomitant oral or intravenous therapy with strong cytochrome P450 3A4(CYP3A4) inhibitors, CYP3A4 substrates with narrow therapeutic indices, or strong CYP3A4 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, phenytoin, carbamazepine. )

• Any other condition such as active cancer

• Life expectancy less than 12 months that may result in protocol non-compliance or a risk for being lost to follow up

• Indication for major surgery(e.g. cancer treatment, carotid surgery, cerebral surgery, major vascular surgery)

Related Conditions & MeSH terms

• Antiplatelet Agents
• Coronary Artery Bypass

Intervention

Drug:
• Aspirin

• Ticagrelor

Locations

Country	Name	City	State
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Nan Jing First Hospital	Nanjing	Jiangsu
China	Changhai Hospital of Shanghai	Shanghai	Shanghai
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Xinhua Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Henan Provincial People's Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The Rate of Gastroduodenal Injury Assessed by Esophagogastroduodenoscopy (EGD)	Not all but the patients recruited in Ruijin Hospital	at 12 months
Primary	The Patency of Saphenous Vein Grafts	assessed by multislice computed tomography angiography (MSCTA) or coronary angiography(CAG). FitzGibbon grade A (stenosis <50%) is defined as "patency".	up to 12 months
Secondary	The Patency of Saphenous Vein Grafts	assessed by MSCTA or CAG. FitzGibbon grade A (stenosis <50%) is defined as "patency".	up to 7 days
Secondary	The Rate of Post-operative Atrial Fibrillation After CABG.	Number of Participants with Post-operative Atrial Fibrillation after CABG	up to 7 days
Secondary	The Rate of Freedom From Angina According to Canadian Cardiovascular Society (CCS) Classification	Number of Participants Free of Angina per CCS Classification	up to 12 months
Secondary	The Number of Major Adverse Cardiovascular Event (MACE)	MACE, composite of CV death, myocardial infarction or stroke (ischaemic or unknown etiology)	up to 12 months
Secondary	Number of the Major Bleeding Events	According to modified TIMI criteria, the "Major Bleeding Events" is defined as the combination of CABG-related bleeding and non-CABG-related major bleeding(Intracranial bleeding, Clinically overt signs of hemorrhage with hemoglobin drop =5 g/dL and Fatal bleeding).	up to 12 months