Trial Outcomes & Findings for Pharmacodynamic Effects of Dabigatran in Patients on Dual Antiplatelet Therapy (NCT NCT01852162)

NCT ID: NCT01852162

Last Updated: 2015-03-17

Results Overview

TRAP-induced platelet aggregation measured by light transmittance aggregometry (LTA) was similar between groups

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 35 participants
• Primary outcome timeframe: 1 week
• Results posted on: 2015-03-17

Participant Flow

This was a prospective, randomized, double-blind, placebo-controlled PD study conducted in patients with CAD on maintenance DAPT with aspirin and clopidogrel. Patients were screened at the Division of Cardiology of the University Of Florida College Of Medicine - Jacksonville from February 2012 to December 2013.

Participant milestones

Measure	Dabigatran Patients randomized to the dabigatran arm received dabigatran 150mg twice/daily for 7 (±3) days.	Placebo Patients randomized to the placebo arm received matching placebo tablets twice/daily for 7 (±3) days.
Overall Study STARTED	18	17
Overall Study COMPLETED	14	16
Overall Study NOT COMPLETED	4	1

Reasons for withdrawal

Measure	Dabigatran Patients randomized to the dabigatran arm received dabigatran 150mg twice/daily for 7 (±3) days.	Placebo Patients randomized to the placebo arm received matching placebo tablets twice/daily for 7 (±3) days.
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	3	1

Baseline Characteristics

Pharmacodynamic Effects of Dabigatran in Patients on Dual Antiplatelet Therapy

Baseline characteristics by cohort

Measure	Dabigatran n=14 Participants Dabigatran 150mg tablets	Placebo n=16 Participants Placebo tablets	Total n=30 Participants Total of all reporting groups
Age, Continuous	65 years STANDARD_DEVIATION 8 • n=5 Participants	59 years STANDARD_DEVIATION 9 • n=7 Participants	63 years STANDARD_DEVIATION 9 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	13 Participants n=7 Participants	24 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	11 Participants n=7 Participants	21 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
Region of Enrollment United States	14 participants n=5 Participants	16 participants n=7 Participants	30 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 week

Population: TRAP-induced platelet aggregation

TRAP-induced platelet aggregation measured by light transmittance aggregometry (LTA) was similar between groups

Outcome measures

Measure	Dabigatran n=14 Participants Dabigatran 150mg	Placebo n=16 Participants Placebo tablets
TRAP-induced Platelet Aggregation	74 percentage of aggregation Standard Deviation 8	77 percentage of aggregation Standard Deviation 6

SECONDARY outcome

Timeframe: 1-week

Population: Platelet aggregation measured by LTA

Multiple measures of platelet reactivity evaluating purinergic and non-purinergic signaling pathways were assessed by light transmittance aggregometry (LTA).

Outcome measures

Measure	Dabigatran n=14 Participants Dabigatran 150mg	Placebo n=16 Participants Placebo tablets
Platelet Reactivity Measured by LTA ADP-induced platelet aggregation	49.5 percentage of aggregation Standard Deviation 16.6	44.6 percentage of aggregation Standard Deviation 15.0
Platelet Reactivity Measured by LTA Arachidonic acid-induced platelet aggregation	6.9 percentage of aggregation Standard Deviation 18.2	6.0 percentage of aggregation Standard Deviation 1.5
Platelet Reactivity Measured by LTA Collagen-induced platelet aggregation	42.6 percentage of aggregation Standard Deviation 22.8	34.9 percentage of aggregation Standard Deviation 22.0

SECONDARY outcome

Timeframe: 1-week

Population: Platelet aggregation measured by multiple electrode aggregometry.

Multiple measures of platelet reactivity evaluating purinergic and non-purinergic signaling pathways were assessed by multiple electrode aggregometry.

Outcome measures

Measure	Dabigatran n=14 Participants Dabigatran 150mg	Placebo n=16 Participants Placebo tablets
Platelet Reactivity Measured by Multiple Electrode Aggregometry. TRAP-induced platelet aggregation	1176.4 arbitrary aggregation units Standard Deviation 274	1210.6 arbitrary aggregation units Standard Deviation 275
Platelet Reactivity Measured by Multiple Electrode Aggregometry. ADP-induced platelet aggregation	482.2 arbitrary aggregation units Standard Deviation 199	454.0 arbitrary aggregation units Standard Deviation 227
Platelet Reactivity Measured by Multiple Electrode Aggregometry. Arachidonic acid-induced platelet aggregation	238.9 arbitrary aggregation units Standard Deviation 88	230.1 arbitrary aggregation units Standard Deviation 115
Platelet Reactivity Measured by Multiple Electrode Aggregometry. Collagen-induced platelet aggregation	559.4 arbitrary aggregation units Standard Deviation 180	532.5 arbitrary aggregation units Standard Deviation 182

SECONDARY outcome

Timeframe: 1-week

Population: Clot kinetic assessed by citrated-kaolin thromboelastography

Parameters related to thrombin activity and velocity of thrombus generation (reaction time: R; time to maximum rate of thrombus generation: TMRTG) were evaluated by thromboelastography.

Outcome measures

Measure	Dabigatran n=14 Participants Dabigatran 150mg	Placebo n=16 Participants Placebo tablets
Clot Kinetic: Thrombin Activity R	12.25 minutes Standard Deviation 2.6	6.76 minutes Standard Deviation 1.1
Clot Kinetic: Thrombin Activity TMRTG	14.32 minutes Standard Deviation 3	8.4 minutes Standard Deviation 1.6

SECONDARY outcome

Timeframe: 1-week

Population: Clot kinetic assessed by citrated-kaolin thromboelastography

Clot strength (maximal amplitude:MA) was assessed by thromboelastography.

Outcome measures

Measure	Dabigatran n=14 Participants Dabigatran 150mg	Placebo n=16 Participants Placebo tablets
Clot Kinetic: Clot Stength	63.7 mm Standard Deviation 4.4	62.9 mm Standard Deviation 6.7

Adverse Events

Dabigatran

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dabigatran n=18 participants at risk Dabigatran 150mg tablets	Placebo n=17 participants at risk Placebo tablets
Cardiac disorders myocardial infarction	5.6% 1/18 • Number of events 1 • 7 days	0.00% 0/17 • 7 days

Other adverse events

Adverse event data not reported

Additional Information

Dominick Angiolillo, MD, PhD

University of Florida

Phone: 904-244-3933

Email: dominick.angiolillo@jax.ufl.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place