Trial Outcomes & Findings for A Phase IV Study of the Onset and Maintenance of the Antiplatelet Effect of Ticagrelor Compared With Clopidogrel in Chinese Patients With ACS (NCT NCT01864005)

NCT ID: NCT01864005

Last Updated: 2015-05-15

Results Overview

Note: the primary endpoint was changed per the statistical analysis plan prior database lock.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

60 participants

Primary outcome timeframe

at 2 hours after first dose of study drug

Results posted on

2015-05-15

Participant Flow

First subject enrolled: 15/05/2013, Last subject last visit: 18/03/2014. There were 5 study centers in China, which participated this study.

There was no run-in or any other pre-assignment periods following participant enrollment.

Participant milestones

Participant milestones
Measure	Ticagrelor Patients received a loading dose of 180mg ticagrelor tablets (two 90mg tablets) taken orally, followed by 90mg of ticagrelor 12 hours after the first dose. The third dose of ticagrelor was given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 90mg of ticagrelor orally bd. The total study period was 6 weeks.	Clopidogrel Patients received a loading dose of 600mg clopidogrel tablets (eight 75mg tablets) taken orally. The second dose of clopidogrel had been given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 75mg of clopidogrel orally od. The total study period was 6 weeks.
Overall Study STARTED	29	31
Overall Study COMPLETED	26	25
Overall Study NOT COMPLETED	3	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Ticagrelor Patients received a loading dose of 180mg ticagrelor tablets (two 90mg tablets) taken orally, followed by 90mg of ticagrelor 12 hours after the first dose. The third dose of ticagrelor was given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 90mg of ticagrelor orally bd. The total study period was 6 weeks.	Clopidogrel Patients received a loading dose of 600mg clopidogrel tablets (eight 75mg tablets) taken orally. The second dose of clopidogrel had been given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 75mg of clopidogrel orally od. The total study period was 6 weeks.
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	0	1
Overall Study Incorrect enrolment	1	0
Overall Study Disease need	1	1
Overall Study Need GP IIb/IIIa	1	3

Baseline Characteristics

A Phase IV Study of the Onset and Maintenance of the Antiplatelet Effect of Ticagrelor Compared With Clopidogrel in Chinese Patients With ACS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ticagrelor n=28 Participants Patients received a loading dose of 180mg ticagrelor tablets (two 90mg tablets) taken orally, followed by 90mg of ticagrelor 12 hours after the first dose. The third dose of ticagrelor was given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 90mg of ticagrelor orally bd. The total study period was 6 weeks.	Clopidogrel n=29 Participants Patients received a loading dose of 600mg clopidogrel tablets (eight 75mg tablets) taken orally. The second dose of clopidogrel had been given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 75mg of clopidogrel orally od. The total study period was 6 weeks.	Total n=57 Participants Total of all reporting groups
Age, Continuous	58.75 years STANDARD_DEVIATION 10.967 • n=5 Participants	58.59 years STANDARD_DEVIATION 9.789 • n=7 Participants	58.67 years STANDARD_DEVIATION 10.291 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	21 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	28 Participants n=5 Participants	29 Participants n=7 Participants	57 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: at 2 hours after first dose of study drug

Population: FAS (full analysis set). Three randomized patients were excluded from FAS due to any of the following reasons: 1) did not meet exclusion requirments but was randomized, 2)post-treatment blood PRU was not available, 3) pre-treatment blood PRU was missing, and 4) use of prohibited medications.

Note: the primary endpoint was changed per the statistical analysis plan prior database lock.

Outcome measures

Outcome measures
Measure	Ticagrelor n=28 Participants Patients received a loading dose of 180mg ticagrelor tablets (two 90mg tablets) taken orally, followed by 90mg of ticagrelor 12 hours after the first dose. The third dose of ticagrelor was given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 90mg of ticagrelor orally bd. The total study period was 6 weeks.	Clopidogrel n=29 Participants Patients received a loading dose of 600mg clopidogrel tablets (eight 75mg tablets) taken orally. The second dose of clopidogrel had been given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 75mg of clopidogrel orally od. The total study period was 6 weeks.
the Percentage Inhibition of the P2Y12 Receptor	48.20 Percentage Inhibition Standard Deviation 45.410	9.78 Percentage Inhibition Standard Deviation 27.574

SECONDARY outcome

Timeframe: at 0.5 hour after first dose of study drug

Population: PPS (per-protocol set). Seven randomized patients were excluded from PPS due to any of the following reasons: 1) did not meet exclusion requirments but was randomized, 2)post-treatment blood PRU was not available, 3) pre-treatment blood PRU was missing, 4) missing blood PRU at 2h after first dose, and 5) use of prohibited medications.

Outcome measures

Outcome measures
Measure	Ticagrelor n=26 Participants Patients received a loading dose of 180mg ticagrelor tablets (two 90mg tablets) taken orally, followed by 90mg of ticagrelor 12 hours after the first dose. The third dose of ticagrelor was given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 90mg of ticagrelor orally bd. The total study period was 6 weeks.	Clopidogrel n=27 Participants Patients received a loading dose of 600mg clopidogrel tablets (eight 75mg tablets) taken orally. The second dose of clopidogrel had been given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 75mg of clopidogrel orally od. The total study period was 6 weeks.
the Percentage Inhibition of the P2Y12 Receptor	8.23 Percentage Inhibition Standard Deviation 25.810	-3.91 Percentage Inhibition Standard Deviation 13.602

SECONDARY outcome

Timeframe: at 8 hours after first dose of study drug

Outcome measures

Outcome measures
Measure	Ticagrelor n=26 Participants Patients received a loading dose of 180mg ticagrelor tablets (two 90mg tablets) taken orally, followed by 90mg of ticagrelor 12 hours after the first dose. The third dose of ticagrelor was given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 90mg of ticagrelor orally bd. The total study period was 6 weeks.	Clopidogrel n=27 Participants Patients received a loading dose of 600mg clopidogrel tablets (eight 75mg tablets) taken orally. The second dose of clopidogrel had been given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 75mg of clopidogrel orally od. The total study period was 6 weeks.
the Percentage Inhibition of the P2Y12 Receptor	67.91 Percentage Inhibition Standard Deviation 34.856	25.38 Percentage Inhibition Standard Deviation 32.738

SECONDARY outcome

Timeframe: at 24 hours after first dose of study drug

Outcome measures

Outcome measures
Measure	Ticagrelor n=26 Participants Patients received a loading dose of 180mg ticagrelor tablets (two 90mg tablets) taken orally, followed by 90mg of ticagrelor 12 hours after the first dose. The third dose of ticagrelor was given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 90mg of ticagrelor orally bd. The total study period was 6 weeks.	Clopidogrel n=27 Participants Patients received a loading dose of 600mg clopidogrel tablets (eight 75mg tablets) taken orally. The second dose of clopidogrel had been given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 75mg of clopidogrel orally od. The total study period was 6 weeks.
the Percentage Inhibition of the P2Y12 Receptor	79.25 Percentage Inhibition Standard Deviation 17.920	28.76 Percentage Inhibition Standard Deviation 26.917

SECONDARY outcome

Timeframe: at 6 weeks after first dose of study drug

Outcome measures

Outcome measures
Measure	Ticagrelor n=26 Participants Patients received a loading dose of 180mg ticagrelor tablets (two 90mg tablets) taken orally, followed by 90mg of ticagrelor 12 hours after the first dose. The third dose of ticagrelor was given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 90mg of ticagrelor orally bd. The total study period was 6 weeks.	Clopidogrel n=27 Participants Patients received a loading dose of 600mg clopidogrel tablets (eight 75mg tablets) taken orally. The second dose of clopidogrel had been given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 75mg of clopidogrel orally od. The total study period was 6 weeks.
the Percentage Inhibition of the P2Y12 Receptor	83.78 Percentage Inhibition Standard Deviation 13.947	24.22 Percentage Inhibition Standard Deviation 33.546

Adverse Events

Ticagrelor

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Clopidogrel

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ticagrelor n=29 participants at risk Patients received a loading dose of 180mg ticagrelor tablets (two 90mg tablets) taken orally, followed by 90mg of ticagrelor 12 hours after the first dose. The third dose of ticagrelor was given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 90mg of ticagrelor orally bd. The total study period was 6 weeks.	Clopidogrel n=31 participants at risk Patients received a loading dose of 600mg clopidogrel tablets (eight 75mg tablets) taken orally. The second dose of clopidogrel had been given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 75mg of clopidogrel orally od. The total study period was 6 weeks.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	3.4% 1/29 • Number of events 1 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Injury, poisoning and procedural complications Drug-induced liver injury	0.00% 0/29 • 6 weeks for all AEs and another 14 days for SAEs.	3.2% 1/31 • Number of events 1 • 6 weeks for all AEs and another 14 days for SAEs.

Other adverse events

Additional Information

Judith Hsia

Astrazeneca

Phone: 1-301-398-0102

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Ticagrelor n=29 participants at risk Patients received a loading dose of 180mg ticagrelor tablets (two 90mg tablets) taken orally, followed by 90mg of ticagrelor 12 hours after the first dose. The third dose of ticagrelor was given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 90mg of ticagrelor orally bd. The total study period was 6 weeks.	Clopidogrel n=31 participants at risk Patients received a loading dose of 600mg clopidogrel tablets (eight 75mg tablets) taken orally. The second dose of clopidogrel had been given to patients after the blood sample had been obtained 24 hours after the first dose. Thereafter, the patients took 75mg of clopidogrel orally od. The total study period was 6 weeks.
Cardiac disorders Hypertensive heart disease	10.3% 3/29 • 6 weeks for all AEs and another 14 days for SAEs.	6.5% 2/31 • 6 weeks for all AEs and another 14 days for SAEs.
Cardiac disorders Arrhythmia	0.00% 0/29 • 6 weeks for all AEs and another 14 days for SAEs.	6.5% 2/31 • 6 weeks for all AEs and another 14 days for SAEs.
Hepatobiliary disorders Hepatic function abnormal	6.9% 2/29 • 6 weeks for all AEs and another 14 days for SAEs.	9.7% 3/31 • 6 weeks for all AEs and another 14 days for SAEs.
Metabolism and nutrition disorders Hyperuricaemia	10.3% 3/29 • 6 weeks for all AEs and another 14 days for SAEs.	6.5% 2/31 • 6 weeks for all AEs and another 14 days for SAEs.
Metabolism and nutrition disorders Hyperlipidaemia	6.9% 2/29 • 6 weeks for all AEs and another 14 days for SAEs.	3.2% 1/31 • 6 weeks for all AEs and another 14 days for SAEs.
Metabolism and nutrition disorders Type 2 diabetes mellitus	6.9% 2/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Musculoskeletal and connective tissue disorders Back pain	6.9% 2/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Blood and lymphatic system disorders Anaemia	0.00% 0/29 • 6 weeks for all AEs and another 14 days for SAEs.	3.2% 1/31 • 6 weeks for all AEs and another 14 days for SAEs.
Cardiac disorders Atrial fibrillation	0.00% 0/29 • 6 weeks for all AEs and another 14 days for SAEs.	3.2% 1/31 • 6 weeks for all AEs and another 14 days for SAEs.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/29 • 6 weeks for all AEs and another 14 days for SAEs.	3.2% 1/31 • 6 weeks for all AEs and another 14 days for SAEs.
Gastrointestinal disorders Constipation	0.00% 0/29 • 6 weeks for all AEs and another 14 days for SAEs.	3.2% 1/31 • 6 weeks for all AEs and another 14 days for SAEs.
Gastrointestinal disorders Diarrhoea	0.00% 0/29 • 6 weeks for all AEs and another 14 days for SAEs.	3.2% 1/31 • 6 weeks for all AEs and another 14 days for SAEs.
Gastrointestinal disorders Toothache	0.00% 0/29 • 6 weeks for all AEs and another 14 days for SAEs.	3.2% 1/31 • 6 weeks for all AEs and another 14 days for SAEs.
Infections and infestations Lung infection	3.4% 1/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Infections and infestations Orchitis	0.00% 0/29 • 6 weeks for all AEs and another 14 days for SAEs.	3.2% 1/31 • 6 weeks for all AEs and another 14 days for SAEs.
Infections and infestations Pharyngitis	3.4% 1/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Infections and infestations Postoperative wound infection	0.00% 0/29 • 6 weeks for all AEs and another 14 days for SAEs.	3.2% 1/31 • 6 weeks for all AEs and another 14 days for SAEs.
Infections and infestations Puncture site infection	0.00% 0/29 • 6 weeks for all AEs and another 14 days for SAEs.	3.2% 1/31 • 6 weeks for all AEs and another 14 days for SAEs.
Infections and infestations Upper respiratory tract infection	3.4% 1/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Investigations Blood creatine increased	3.4% 1/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Investigations Blood creatinine increased	3.4% 1/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Investigations Blood triglycerides increased	3.4% 1/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Metabolism and nutrition disorders Hypoglycemia	3.4% 1/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Metabolism and nutrition disorders Metabolic disorder	0.00% 0/29 • 6 weeks for all AEs and another 14 days for SAEs.	3.2% 1/31 • 6 weeks for all AEs and another 14 days for SAEs.
Nervous system disorders Headache	3.4% 1/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Respiratory, thoracic and mediastinal disorders Cough	3.4% 1/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/29 • 6 weeks for all AEs and another 14 days for SAEs.	3.2% 1/31 • 6 weeks for all AEs and another 14 days for SAEs.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.4% 1/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Skin and subcutaneous tissue disorders Skin haemorrhage	3.4% 1/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Vascular disorders Ecchymosis	3.4% 1/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Vascular disorders Haematoma	0.00% 0/29 • 6 weeks for all AEs and another 14 days for SAEs.	3.2% 1/31 • 6 weeks for all AEs and another 14 days for SAEs.
Vascular disorders Hypertension	3.4% 1/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.
Vascular disorders Hypotension	3.4% 1/29 • 6 weeks for all AEs and another 14 days for SAEs.	0.00% 0/31 • 6 weeks for all AEs and another 14 days for SAEs.