Ticagrelor vs clopidogrel in non-ST elevation acute coronary syndrome patients undergoing PCI with bivalirudin. - NSTE-ACS

Study identifier:D5130L00065

ClinicalTrials.gov identifier:NCT02052635

EudraCT identifier:N/A

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A Phase IV, Randomised, Multi-Centre, Open label Study, Comparing ticagrelor versus clopidogrel in non-ST elevation acute coronary syndrome (NSTE-ACS) patients undergoing percutaneous coronary intervention (PCI) with bivalirudin

Medical condition

Non-ST elevation Acute Coronary Syndrome

Phase

Phase 4

Healthy volunteers

Study drug

ticagrelor, clopidogrel

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 01 Sept 2014

Primary Completion Date: 01 Apr 2015

Study Completion Date: 01 Apr 2015

Study design

Allocation: Randomized
Endpoint Classification: Pharmacodynamics
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2016 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Jacksonville, FL, United States

Location

Research Site

Pittsburgh, PA, United States

Location

Research Site

Rapid City, SD, United States

Location

Research Site

Lake Mary, FL, United States

Location

Research Site

Macon, GA, United States

Location

Research Site

Hershey, PA, United States

Location

Research Site

Philadelphia, PA, United States

Location

Research Site

Oklahoma City, OK, United States

Arms	Assigned Interventions
Experimental: Ticagrelor 90 mg oral tablet	Drug: ticagrelor Single loading dose of 180mg of ticagrelor at time of bivalirudin administration. Beginning 12 hrs following study drug administration, all pts in the ticagrelor arm will receive ticagrelor 90 mg (maintenance dose) approximately every 12 hrs until Follow-up telephone contact. Other Name: Brilinta
Active Comparator: Clopidogrel 300 mg oral tablet	Drug: clopidogrel Single loading oral dose of 600 mg of clopidogrel will be given at time of bivalirudin administration. Beginning 4 hrs following study drug administration, all pts in the clopidorgrel arm will receive ticagrelor 180 mg for the loading dose, followed by 90 mg maintenance dose approximately every 12 hours until the Follow-up telephone contact. Other Name: Plavix

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted in the USA. While 17 sites were activated, 9 sites enrolled patients, and only 7 sites successfully randomised patients. There were 34 patients screened, 21 screen failures and 13 randomised patients from 03 September 2014 and 20 April 2015. The study was terminated due to recruitment challenges and low enrolment concerns.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Ticagrelor	A single oral dose of 180 mg (90 mg tablet x2) of ticagrelor was administered at the time of the initial bivalirudin bolus administration.
Clopidogrel	A single oral dose of 600 mg (300 mg tablet x2) of clopidogrel was administered at the time of the initial bivalirudin bolus administration.

Participant Flow: Overall Study

	Ticagrelor	Clopidogrel
STARTED	7	6
COMPLETED	7	6
NOT COMPLETED	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Ticagrelor	A single oral dose of 180 mg (90 mg tablet x2) of ticagrelor was administered at the time of the initial bivalirudin bolus administration.
Clopidogrel	A single oral dose of 600 mg (300 mg tablet x2) of clopidogrel was administered at the time of the initial bivalirudin bolus administration.

Baseline Measures

	Ticagrelor	Clopidogrel	Total
Number of Participants [units: Participants]	7	6	13
Age Continuous [units: Years] Mean ± Standard Deviation	63.9 ± 2.7	61.2 ± 14.7	62.6 ± 9.8
Gender, Male/Female [units: Participants]
Female	3	2	5
Male	4	4	8

Outcome Measures

1. Primary Outcome Measure: P2Y12 Reaction Units (PRU) using VerifyNow™ at 0.5 hours after loading dose [ Time Frame: 0.5 hours post loading dose ]

Measure Type	Primary
Measure Name	P2Y12 Reaction Units (PRU) using VerifyNow™ at 0.5 hours after loading dose
Measure Description	PRU at 0.5 hours after a single oral loading dose of either ticagrelor 180 mg or clopidogrel 600 mg given at the time of the bivalirudin bolus
Time Frame	0.5 hours post loading dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
10 patients were included in the pharmacodynamic (PD) analysis: 6 patients in the ticagrelor group and 4 patients in the clopidogrel group. 3 out 13 randomized pateints are excluded (1 patient without any PRU data, 2 pateints with protocol deviations)

Reporting Groups

	Description
Ticagrelor	A single oral dose of 180 mg (90 mg tablet x2) of ticagrelor was administered at the time of the initial bivalirudin bolus administration.
Clopidogrel	A single oral dose of 600 mg (300 mg tablet x2) of clopidogrel was administered at the time of the initial bivalirudin bolus administration.

Measured Values

	Ticagrelor	Clopidogrel
Number of Participants Analyzed [units:participants]	6	4
P2Y12 Reaction Units (PRU) using VerifyNow™ at 0.5 hours after loading dose [units: PRUs] Mean (Standard Deviation)	289.2 (44.6)	292.8 (38.7)

No statistical analysis provided for P2Y12 Reaction Units (PRU) using VerifyNow™ at 0.5 hours after loading dose

2. Primary Outcome Measure: P2Y12 Reaction Units (PRU) using VerifyNow™ at 1 hour after loading dose [ Time Frame: 1 hour post loading dose ]

Measure Type	Primary
Measure Name	P2Y12 Reaction Units (PRU) using VerifyNow™ at 1 hour after loading dose
Measure Description	PRU at 1 hour after a single oral loading dose of either ticagrelor 180 mg or clopidogrel 600 mg given at the time of the bivalirudin bolus
Time Frame	1 hour post loading dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
10 patients were included in the PD analysis: 6 patients in the ticagrelor group and 4 patients in the clopidogrel group. Out of the 10 patients in the PD analysis, 1 patient in Ticagrelor group does not have PRU value at 1 hour post loading dose.

Reporting Groups

	Description
Ticagrelor	A single oral dose of 180 mg (90 mg tablet x2) of ticagrelor was administered at the time of the initial bivalirudin bolus administration.
Clopidogrel	A single oral dose of 600 mg (300 mg tablet x2) of clopidogrel was administered at the time of the initial bivalirudin bolus administration.

Measured Values

	Ticagrelor	Clopidogrel
Number of Participants Analyzed [units:participants]	5	4
P2Y12 Reaction Units (PRU) using VerifyNow™ at 1 hour after loading dose [units: PRUs] Mean (Standard Deviation)	174.4 (88.9)	249.8 (68.7)

No statistical analysis provided for P2Y12 Reaction Units (PRU) using VerifyNow™ at 1 hour after loading dose

Serious Adverse Events

Time Frame	Serious adverse events (SAEs) from informed consent to follow-up contact (4-7 days after treatment) and non-serious adverse events (AEs) of interest from time of randomisation to follow-up. All SAEs and non-serious AEs of interest will be recorded.
Additional Description	This study just collects the following non-serious AEs of interest: bleeding events, dyspnoea, renal impairment/increased creatinine, brady arrhythmic event, increased liver function tests, gout/uric acid increases, pneumonia, gynecomastia, abnormal uterine bleeding, all malignancies excluding non-melanoma skin cancers.

Reporting Groups

	Description
Ticagrelor	A single oral dose of 180 mg (90 mg tablet x2) of ticagrelor was administered at the time of the initial bivalirudin bolus administration.
Clopidogrel	A single oral dose of 600 mg (300 mg tablet x2) of clopidogrel was administered at the time of the initial bivalirudin bolus administration.

Serious Adverse Events

	Ticagrelor	Clopidogrel
Total, serious adverse events
# participants affected / at risk	0/7 (0.00%)	0/6 (0.00%)

Other Adverse Events

Time Frame	Serious adverse events (SAEs) from informed consent to follow-up contact (4-7 days after treatment) and non-serious adverse events (AEs) of interest from time of randomisation to follow-up. All SAEs and non-serious AEs of interest will be recorded.
Additional Description	This study just collects the following non-serious AEs of interest: bleeding events, dyspnoea, renal impairment/increased creatinine, brady arrhythmic event, increased liver function tests, gout/uric acid increases, pneumonia, gynecomastia, abnormal uterine bleeding, all malignancies excluding non-melanoma skin cancers.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Ticagrelor	A single oral dose of 180 mg (90 mg tablet x2) of ticagrelor was administered at the time of the initial bivalirudin bolus administration.
Clopidogrel	A single oral dose of 600 mg (300 mg tablet x2) of clopidogrel was administered at the time of the initial bivalirudin bolus administration.