DACAB: Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery

• Sponsor: Ruijin Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02201771
• Collaborator: (none)
• Enrollment: 500
• Locations: 6
• Arms: 3
• Duration (Months): 30.1
• Patients Per Site: 83.3
• Patients Per Site Per Month: 2.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Bypass; Antiplatelet Agents	Drug: Aspirin; Drug: Ticagrelor	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 500 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Compare the Efficacy of Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Jan 1, 2017
• Actual Study Completion Date: Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Aspirin aspirin 100mg tablet by mouth daily for 12 months	Drug: Aspirin
Experimental: Ticagrelor plus Aspirin ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months	Drug: Aspirin; Drug: Ticagrelor
Experimental: Ticagrelor ticagrelor 90mg tablet by mouth twice daily for 12 months	Drug: Ticagrelor

Outcome Measures

Primary Outcome Measures

1. The Patency of Saphenous Vein Grafts [up to 12 months]

   assessed by multislice computed tomography angiography (MSCTA) or coronary angiography(CAG). FitzGibbon grade A (stenosis <50%) is defined as "patency".

Secondary Outcome Measures

1. The Patency of Saphenous Vein Grafts [up to 7 days]

   assessed by MSCTA or CAG. FitzGibbon grade A (stenosis <50%) is defined as "patency".

2. The Rate of Post-operative Atrial Fibrillation After CABG. [up to 7 days]

   Number of Participants with Post-operative Atrial Fibrillation after CABG

3. The Rate of Freedom From Angina According to Canadian Cardiovascular Society (CCS) Classification [up to 12 months]

   Number of Participants Free of Angina per CCS Classification

4. The Number of Major Adverse Cardiovascular Event (MACE) [up to 12 months]

   MACE, composite of CV death, myocardial infarction or stroke (ischaemic or unknown etiology)

5. Number of the Major Bleeding Events [up to 12 months]

   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).

Other Outcome Measures

1. The Rate of Gastroduodenal Injury Assessed by Esophagogastroduodenoscopy (EGD) [at 12 months]

   Not all but the patients recruited in Ruijin Hospital

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Henan Provincial People's Hospital	Zhengzhou	Henan	China
2	Jiangsu Province Hospital	Nanjing	Jiangsu	China
3	Nan Jing First Hospital	Nanjing	Jiangsu	China
4	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China	200025
5	Xinhua Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China	200092
6	Changhai Hospital of Shanghai	Shanghai	Shanghai	China	200433

Sponsors and Collaborators

• Ruijin Hospital

Investigators

• Principal Investigator: Qiang Zhao, MD.PhD, Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China
• Study Director: Yunpeng Zhu, MD., Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China

Study Documents (Full-Text)

• Study Protocol - Mar 7, 2017
• Statistical Analysis Plan - Aug 28, 2017

More Information

Publications

None provided.

• Responsible Party: Qiang Zhao,MD, Vice President of Ruijin Hospital, Professor and director, Department of Cardiac Surgery, Ruijin Hospital
• ClinicalTrials.gov Identifier: NCT02201771
• Other Study ID Numbers: ISSBRIL0211
• First Posted: Jul 28, 2014
• Last Update Posted: Aug 13, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Qiang Zhao,MD, Vice President of Ruijin Hospital, Professor and director, Department of Cardiac Surgery, Ruijin Hospital: CABG; Antiplatelet; Ticagrelor
• Additional relevant MeSH terms: Aspirin; Ticagrelor

Study Results

Participant Flow

Arm/Group Title	Aspirin	Ticagrelor Plus Aspirin	Ticagrelor
Arm/Group Description	aspirin 100mg tablet by mouth daily for 12 months Aspirin	ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months Aspirin Ticagrelor	ticagrelor 90mg tablet by mouth twice daily for 12 months Ticagrelor
Period Title: Overall Study
STARTED	166	168	166
COMPLETED	153	158	156
NOT COMPLETED	13	10	10

Baseline Characteristics

Arm/Group Title	Aspirin	Ticagrelor Plus Aspirin	Ticagrelor	Total
Arm/Group Description	aspirin 100mg tablet by mouth daily for 12 months Aspirin	ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months Aspirin Ticagrelor	ticagrelor 90mg tablet by mouth twice daily for 12 months Ticagrelor	Total of all reporting groups
Overall Participants	166	168	166	500
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (8.1)	63.5 (8.2)	63.3 (8.3)	63.6 (8.2)
Sex: Female, Male (Count of Participants)
Female	25 15.1%	34 20.2%	32 19.3%	91 18.2%
Male	141 84.9%	134 79.8%	134 80.7%	409 81.8%
Region of Enrollment (participants) [Number]
China	166 100%	168 100%	166 100%	500 100%

Outcome Measures

1. Primary Outcome

Title	The Patency of Saphenous Vein Grafts
Description	assessed by multislice computed tomography angiography (MSCTA) or coronary angiography(CAG). FitzGibbon grade A (stenosis <50%) is defined as "patency".
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

ITT analysis, Patients with missing data were considered to have occluded saphenous vein grafts.

Arm/Group Title	Aspirin	Ticagrelor Plus Aspirin	Ticagrelor
Arm/Group Description	aspirin 100mg tablet by mouth daily for 12 months Aspirin	ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months Aspirin Ticagrelor	ticagrelor 90mg tablet by mouth twice daily for 12 months Ticagrelor
Measure Participants	166	168	166
Measure saphenous vein grafts	485	487	488
Number (95% Confidence Interval) [percentage of patent SV grafts]	76.5	88.7	82.8

2. Secondary Outcome

Title	The Patency of Saphenous Vein Grafts
Description	assessed by MSCTA or CAG. FitzGibbon grade A (stenosis <50%) is defined as "patency".
Time Frame	up to 7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aspirin	Ticagrelor Plus Aspirin	Ticagrelor
Arm/Group Description	aspirin 100mg tablet by mouth daily for 12 months Aspirin	ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months Aspirin Ticagrelor	ticagrelor 90mg tablet by mouth twice daily for 12 months Ticagrelor
Measure Participants	166	168	166
Measure saphenous vein grafts	485	487	488
Number (95% Confidence Interval) [percentage of patent SV grafts]	91.1	94.9	94.3

3. Secondary Outcome

Title	The Rate of Post-operative Atrial Fibrillation After CABG.
Description	Number of Participants with Post-operative Atrial Fibrillation after CABG
Time Frame	up to 7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aspirin	Ticagrelor Plus Aspirin	Ticagrelor
Arm/Group Description	aspirin 100mg tablet by mouth daily for 12 months Aspirin	ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months Aspirin Ticagrelor	ticagrelor 90mg tablet by mouth twice daily for 12 months Ticagrelor
Measure Participants	166	168	166
Count of Participants [Participants]	23 13.9%	20 11.9%	13 7.8%

4. Secondary Outcome

Title	The Rate of Freedom From Angina According to Canadian Cardiovascular Society (CCS) Classification
Description	Number of Participants Free of Angina per CCS Classification
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aspirin	Ticagrelor Plus Aspirin	Ticagrelor
Arm/Group Description	aspirin 100mg tablet by mouth daily for 12 months Aspirin	ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months Aspirin Ticagrelor	ticagrelor 90mg tablet by mouth twice daily for 12 months Ticagrelor
Measure Participants	166	168	166
Count of Participants [Participants]	154 92.8%	158 94%	155 93.4%

5. Secondary Outcome

Title	The Number of Major Adverse Cardiovascular Event (MACE)
Description	MACE, composite of CV death, myocardial infarction or stroke (ischaemic or unknown etiology)
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aspirin	Ticagrelor Plus Aspirin	Ticagrelor
Arm/Group Description	aspirin 100mg tablet by mouth daily for 12 months Aspirin	ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months Aspirin Ticagrelor	ticagrelor 90mg tablet by mouth twice daily for 12 months Ticagrelor
Measure Participants	166	168	166
Number [events]	9	4	3

6. Secondary Outcome

Title	Number of the Major Bleeding Events
Description	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).
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aspirin	Ticagrelor Plus Aspirin	Ticagrelor
Arm/Group Description	aspirin 100mg tablet by mouth daily for 12 months Aspirin	ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months Aspirin Ticagrelor	ticagrelor 90mg tablet by mouth twice daily for 12 months Ticagrelor
Measure Participants	166	168	166
Number [events]	0	3	2

7. Other Pre-specified Outcome

Title	The Rate of Gastroduodenal Injury Assessed by Esophagogastroduodenoscopy (EGD)
Description	Not all but the patients recruited in Ruijin Hospital
Time Frame	at 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	1 year
Arm/Group Title	Aspirin		Ticagrelor Plus Aspirin		Ticagrelor
Arm/Group Description	aspirin 100mg tablet by mouth daily for 12 months Aspirin		ticagrelor 90mg tablet by mouth twice daily and aspirin 100mg tablet by mouth daily for 12 months Aspirin Ticagrelor		ticagrelor 90mg tablet by mouth twice daily for 12 months Ticagrelor
All Cause Mortality
	Aspirin		Ticagrelor Plus Aspirin		Ticagrelor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/166 (1.8%)		2/168 (1.2%)		0/166 (0%)
Serious Adverse Events
	Aspirin		Ticagrelor Plus Aspirin		Ticagrelor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/166 (5.4%)		3/168 (1.8%)		3/166 (1.8%)
Cardiac disorders
Nonfatal myocardial infarction	3/166 (1.8%)		2/168 (1.2%)		2/166 (1.2%)
Nonfatal stroke	4/166 (2.4%)		0/168 (0%)		2/166 (1.2%)
Cardiovascular death	2/166 (1.2%)		1/168 (0.6%)		0/166 (0%)
Other (Not Including Serious) Adverse Events
	Aspirin		Ticagrelor Plus Aspirin		Ticagrelor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/166 (47%)		91/168 (54.2%)		74/166 (44.6%)
Blood and lymphatic system disorders
Anaemia	14/166 (8.4%)		10/168 (6%)		12/166 (7.2%)
Cardiac disorders
Atrial Fibrillation	25/166 (15.1%)		22/168 (13.1%)		15/166 (9%)
Perioperative myocardial injury	11/166 (6.6%)		25/168 (14.9%)		14/166 (8.4%)
Injury, poisoning and procedural complications
Incision complication	10/166 (6%)		9/168 (5.4%)		6/166 (3.6%)
Metabolism and nutrition disorders
Hypoproteinemia	17/166 (10.2%)		22/168 (13.1%)		18/166 (10.8%)
Renal and urinary disorders
Renal disfunction	6/166 (3.6%)		12/168 (7.1%)		9/166 (5.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.