Clinical trial NCT02201771: Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery
Official title: Compare the Efficacy of Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Bypass
Antiplatelet Agents
Keywords: CABG
Antiplatelet
Ticagrelor
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2014-07-28
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: The Patency of Saphenous Vein Grafts
timeFrame: up to 12 months
Secondary outcomes:
measure: The Patency of Saphenous Vein Grafts
timeFrame: up to 7 days
measure: The Rate of Post-operative Atrial Fibrillation After CABG.
timeFrame: up to 7 days
measure: The Rate of Freedom From Angina According to Canadian Cardiovascular Society (CCS) Classification
timeFrame: up to 12 months
measure: The Number of Major Adverse Cardiovascular Event (MACE)
timeFrame: up to 12 months
measure: Number of the Major Bleeding Events
timeFrame: up to 12 months
Other outcomes:
measure: The Rate of Gastroduodenal Injury Assessed by Esophagogastroduodenoscopy (EGD)
timeFrame: at 12 months
Locations:
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nan Jing First Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Xinhua Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Changhai Hospital of Shanghai
state: Shanghai
Study officials:
affiliation: Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China
name: Qiang Zhao, MD.PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China
name: Yunpeng Zhu, MD.
role: STUDY_DIRECTOR
References:
citation: 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.