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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aspirin | Active Comparator | aspirin 100mg tablet by mouth daily for 12 months |
|
| Ticagrelor plus Aspirin | Experimental | ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months |
|
| Ticagrelor | Experimental | ticagrelor 90mg tablet by mouth twice daily for 12 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aspirin | Drug |
| ||
| Ticagrelor |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| The Patency of Saphenous Vein Grafts | assessed by MSCTA or CAG. FitzGibbon grade A (stenosis <50%) is defined as "patency". | up to 7 days |
| The Rate of Post-operative Atrial Fibrillation After CABG. |
| Measure | Description | Time Frame |
|---|---|---|
| The Rate of Gastroduodenal Injury Assessed by Esophagogastroduodenoscopy (EGD) | Not all but the patients recruited in Ruijin Hospital | at 12 months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Qiang Zhao, MD.PhD | Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China | Principal Investigator |
| Yunpeng Zhu, MD. | Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Henan Provincial People's Hospital | Zhengzhou | Henan | China | |||
| Jiangsu Province Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29710164 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Aspirin | aspirin 100mg tablet by mouth daily for 12 months Aspirin |
| FG001 | Ticagrelor Plus Aspirin | ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months Aspirin Ticagrelor |
| FG002 | Ticagrelor | ticagrelor 90mg tablet by mouth twice daily for 12 months Ticagrelor |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Aspirin | aspirin 100mg tablet by mouth daily for 12 months Aspirin |
| BG001 | Ticagrelor Plus Aspirin | ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months Aspirin Ticagrelor |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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". | ITT analysis, Patients with missing data were considered to have occluded saphenous vein grafts. | Posted | Number | 95% Confidence Interval | percentage of patent SV grafts | up to 12 months | saphenous vein grafts | saphenous vein grafts |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Aspirin | aspirin 100mg tablet by mouth daily for 12 months Aspirin | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nonfatal myocardial infarction | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial Fibrillation | Cardiac disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Yunpeng Zhu | Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China | 008613816819346 | zypB1014@rjh.com.cn |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 7, 2017 | Jan 3, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 28, 2017 | Jan 3, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D001241 | Aspirin |
| D000077486 | Ticagrelor |
| ID | Term |
|---|---|
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
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|
Number of Participants with Post-operative Atrial Fibrillation after CABG
| up to 7 days |
| 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 |
| 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 |
| 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 |
| Nanjing |
| Jiangsu |
| China |
| Nan Jing First Hospital | Nanjing | Jiangsu | China |
| Ruijin Hospital, Shanghai Jiaotong University School of Medicine | Shanghai | Shanghai Municipality | 200025 | China |
| Xinhua Hospital, Shanghai Jiaotong University School of Medicine | Shanghai | Shanghai Municipality | 200092 | China |
| Changhai Hospital of Shanghai | Shanghai | Shanghai Municipality | 200433 | China |
| BG002 | Ticagrelor | ticagrelor 90mg tablet by mouth twice daily for 12 months Ticagrelor |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | Ticagrelor | ticagrelor 90mg tablet by mouth twice daily for 12 months Ticagrelor |
|
|
| Secondary | The Patency of Saphenous Vein Grafts | assessed by MSCTA or CAG. FitzGibbon grade A (stenosis <50%) is defined as "patency". | Posted | Number | 95% Confidence Interval | percentage of patent SV grafts | up to 7 days | saphenous vein grafts | saphenous vein grafts |
|
|
|
| Secondary | The Rate of Post-operative Atrial Fibrillation After CABG. | Number of Participants with Post-operative Atrial Fibrillation after CABG | Posted | Count of Participants | Participants | 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 | Posted | Count of Participants | Participants | 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) | Posted | Number | events | 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). | Posted | Number | events | up to 12 months |
|
|
|
| Other Pre-specified | The Rate of Gastroduodenal Injury Assessed by Esophagogastroduodenoscopy (EGD) | Not all but the patients recruited in Ruijin Hospital | Not Posted | at 12 months | Participants |
| 166 |
| 9 |
| 166 |
| 78 |
| 166 |
| EG001 | Ticagrelor Plus Aspirin | ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months Aspirin Ticagrelor | 2 | 168 | 3 | 168 | 91 | 168 |
| EG002 | Ticagrelor | ticagrelor 90mg tablet by mouth twice daily for 12 months Ticagrelor | 0 | 166 | 3 | 166 | 74 | 166 |
| Nonfatal stroke | Cardiac disorders | Systematic Assessment |
|
| Cardiovascular death | Cardiac disorders | Systematic Assessment |
|
| Perioperative myocardial injury | Cardiac disorders | Non-systematic Assessment | cTn > 10*URL but not myocardial infarction |
|
| Hypoproteinemia | Metabolism and nutrition disorders | Non-systematic Assessment | serum albumin<25g/L |
|
| Anaemia | Blood and lymphatic system disorders | Non-systematic Assessment | Hemoglobin < 70g/L |
|
| Renal disfunction | Renal and urinary disorders | Non-systematic Assessment | Serum creatinine>200umol/L |
|
| Incision complication | Injury, poisoning and procedural complications | Non-systematic Assessment | poor healing of incision |
|
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| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D000241 | Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |