Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery

NCT ID: NCT02201771

Last Updated: 2019-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2017-01-31

Brief 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.

Detailed 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.

Conditions

Coronary Artery Bypass; Antiplatelet Agents

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aspirin

aspirin 100mg tablet by mouth daily for 12 months

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

Ticagrelor plus Aspirin

ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months

Group Type: EXPERIMENTAL

Aspirin

Intervention Type: DRUG

Ticagrelor

Intervention Type: DRUG

Ticagrelor

ticagrelor 90mg tablet by mouth twice daily for 12 months

Group Type: EXPERIMENTAL

Ticagrelor

Intervention Type: DRUG

Interventions

Aspirin

Intervention Type: DRUG

Ticagrelor

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Qiang Zhao,MD

Vice President of Ruijin Hospital, Professor and director, Department of Cardiac Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Qiang Zhao, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China

Yunpeng Zhu, MD.

Role: STUDY_DIRECTOR

Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China

Locations

Henan Provincial People's Hospital

Zhengzhou, Henan, China

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Nan Jing First Hospital

Nanjing, Jiangsu, China

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

Xinhua Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

Changhai Hospital of Shanghai

Shanghai, Shanghai Municipality, China

Countries

China

References

Zhao Q, Zhu Y, Xu Z, Cheng Z, Mei J, Chen X, Wang X. Effect of Ticagrelor Plus Aspirin, Ticagrelor Alone, or Aspirin Alone on Saphenous Vein Graft Patency 1 Year After Coronary Artery Bypass Grafting: A Randomized Clinical Trial. JAMA. 2018 Apr 24;319(16):1677-1686. doi: 10.1001/jama.2018.3197.

Reference Type: DERIVED

PMID: 29710164 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ISSBRIL0211

Identifier Type: -

Identifier Source: org_study_id