Trial Outcomes & Findings for Pharmacodynamic Effects of Low-dose Rivaroxaban With Antiplatelet Therapies (NCT NCT03718429)

Last Updated: 2022-06-27

Results Overview

Comparison of platelet-mediated global thrombogenicity measured by light transmittance aggregometry following collagen-related peptide+adenosine diphosphate+ tissue factor (CATF) stimuli between aspirin plus clopidogrel vs. aspirin plus clopidogrel plus rivaroxaban. This was reported as maximal aggregation %. The combination of agonists included in the CATF cocktail leads to activation of multiple platelet pathways including thrombin generation and is therefore a marker of thrombus formation mediated by platelets.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

86 participants

Primary outcome timeframe

20 days

Results posted on

2022-06-27

Participant Flow

Between January 14, 2019 and August 30, 2020 a total of 86 patients were consented for the study.

1 patient withdrew the consent before initiation of the study and 3 patients were not eligible to start the study due to the presence of an exclusion criteria.

Participant milestones

Participant milestones
Measure	Aspirin The cohort of patients on aspirin (81 mg daily) was treated with adjunctive vascular dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy was suspended for 7-10 days.	Aspirin Plus Clopidogrel The cohort of patients on aspirin (81 mg daily) plus clopidogrel (75 mg dailiy) was treated with adjunctive vascular dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy was suspended for 7-10 days.	Aspirin Plus Ticagrelor The cohort of patients on aspirin (81 mg daily) plus ticagrelor (90 mg bid) was treated with adjunctive vascular dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy was suspended for 7-10 days.	Rivaroxaban 20 mg The cohort of patients on rivaroxaban remained on rivaroxaban 20 mg daily.
Baseline Treatment STARTED	20	21	21	20
Baseline Treatment COMPLETED	20	21	21	20
Baseline Treatment NOT COMPLETED	0	0	0	0
Adjunctive Rivaroxaban 2.5 mg STARTED	20	21	21	0
Adjunctive Rivaroxaban 2.5 mg COMPLETED	20	20	20	0
Adjunctive Rivaroxaban 2.5 mg NOT COMPLETED	0	1	1	0
Stopping Aspirin STARTED	20	20	20	0
Stopping Aspirin COMPLETED	20	20	20	0
Stopping Aspirin NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Aspirin The cohort of patients on aspirin (81 mg daily) was treated with adjunctive vascular dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy was suspended for 7-10 days.	Aspirin Plus Clopidogrel The cohort of patients on aspirin (81 mg daily) plus clopidogrel (75 mg dailiy) was treated with adjunctive vascular dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy was suspended for 7-10 days.	Aspirin Plus Ticagrelor The cohort of patients on aspirin (81 mg daily) plus ticagrelor (90 mg bid) was treated with adjunctive vascular dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy was suspended for 7-10 days.	Rivaroxaban 20 mg The cohort of patients on rivaroxaban remained on rivaroxaban 20 mg daily.
Adjunctive Rivaroxaban 2.5 mg Withdrawal by Subject	0	1	1	0

Baseline Characteristics

Pharmacodynamic Effects of Low-dose Rivaroxaban With Antiplatelet Therapies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aspirin n=20 Participants The cohort of patients on aspirin was treated with adjunctive vascular dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy was suspended for 7-10 days.	Aspirin Plus Clopidogrel n=20 Participants The cohort of patients on aspirin plus clopidogrel was treated with adjunctive vascular dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy was suspended for 7-10 days.	Aspirin Plus Ticagrelor n=20 Participants The cohort of patients on aspirin plus ticagrelor was treated with adjunctive vascular dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy was suspended for 7-10 days.	Rivaroxaban 20 mg n=20 Participants The cohort of patients on rivaroxaban remained on rivaroxaban 20 mg daily.	Total n=80 Participants Total of all reporting groups
Age, Continuous	63 years STANDARD_DEVIATION 9 • n=5 Participants	64 years STANDARD_DEVIATION 9 • n=7 Participants	59 years STANDARD_DEVIATION 9 • n=5 Participants	67 years STANDARD_DEVIATION 10 • n=4 Participants	63 years STANDARD_DEVIATION 9 • n=21 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants	28 Participants n=21 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	14 Participants n=7 Participants	16 Participants n=5 Participants	11 Participants n=4 Participants	52 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	4 Participants n=4 Participants	36 Participants n=21 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	16 Participants n=4 Participants	42 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
peripheral arterial disease	4 Participants n=5 Participants	12 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	17 Participants n=21 Participants

PRIMARY outcome

Timeframe: 20 days

Population: For the purpose of this analysis, assessments were conducted in patients with an antithrombotic treatment regimen that paralleled that of the VOYAGER PAD trial, which included patients on triple therapy (DAPT with aspirin 81mg/qd and clopidogrel 75 mg/qd plus rivaroxaban 2.5 mg/bid) and DPI (aspirin 81 mg/qd plus rivaroxaban 2.5 mg/bid). Comparative PD assessments were also made with patients on standard DAPT (aspirin and clopidogrel). Only patients with complete data were analyzed.

Outcome measures

Outcome measures
Measure	Aspirin Plus Clopidogrel n=20 Participants Cohort of patients on aspirin plus clopidogrel	Aspirin Plus Clopidogrel Plus Rivaroxaban n=20 Participants Cohort of patients on aspirin, clopidogrel and rivaroxaban	Clopidogrel Plus Rivaroxaban n=20 Participants Cohort of patients on clopidogrel plus rivaroxaban	Aspirin n=20 Participants Cohort of patients on aspirin only	Aspirin Plus Rivaroxaban n=20 Participants Cohort of patients on aspirin plus rivaroxaban	Rivaroxaban n=20 Participants Cohort of patients on rivaroxaban alone	Aspirin Plus Ticagrelor n=20 Participants Cohort of patients on aspirin plus ticagrelor	Aspirin Plus Ticagrelor Plus Rivaroxaban n=20 Participants Cohort of patients on aspirin plus ticagrelor plus rivaroxaban	Ticagrelor Plus Rivaroxaban n=20 Participants Cohort of patients on ticagrelor plus rivaroxaban	Rivaroxaban 20 mg n=20 Participants Cohort of patients on rivaroxaban 20 mg
Platelet-Mediated Global Thrombogenicity	66 percentage of aggregation Standard Deviation 18	59 percentage of aggregation Standard Deviation 19	69 percentage of aggregation Standard Deviation 18	71 percentage of aggregation Standard Deviation 12	63 percentage of aggregation Standard Deviation 21	74 percentage of aggregation Standard Deviation 10	37 percentage of aggregation Standard Deviation 24	32 percentage of aggregation Standard Deviation 25	35 percentage of aggregation Standard Deviation 24	75 percentage of aggregation Standard Deviation 14

PRIMARY outcome

Timeframe: 20 days

P2Y12 reaction units (PRU) by VerifyNow of dual antiplatelet therapy vs. dual antiplatelet therapy plus rivaroxaban. VerifyNow is a turbidimetric based optical detection system which measures platelet aggregation induced by ADP as an increase in light transmittance.

Outcome measures

Outcome measures
Measure	Aspirin Plus Clopidogrel n=20 Participants Cohort of patients on aspirin plus clopidogrel	Aspirin Plus Clopidogrel Plus Rivaroxaban n=20 Participants Cohort of patients on aspirin, clopidogrel and rivaroxaban	Clopidogrel Plus Rivaroxaban n=20 Participants Cohort of patients on clopidogrel plus rivaroxaban	Aspirin n=20 Participants Cohort of patients on aspirin only	Aspirin Plus Rivaroxaban n=20 Participants Cohort of patients on aspirin plus rivaroxaban	Rivaroxaban n=20 Participants Cohort of patients on rivaroxaban alone	Aspirin Plus Ticagrelor n=20 Participants Cohort of patients on aspirin plus ticagrelor	Aspirin Plus Ticagrelor Plus Rivaroxaban n=20 Participants Cohort of patients on aspirin plus ticagrelor plus rivaroxaban	Ticagrelor Plus Rivaroxaban n=20 Participants Cohort of patients on ticagrelor plus rivaroxaban	Rivaroxaban 20 mg n=20 Participants Cohort of patients on rivaroxaban 20 mg
Platelet Aggregation Measured by VerifyNow PRU	156 PRU Standard Deviation 75	139 PRU Standard Deviation 72	156 PRU Standard Deviation 73	223 PRU Standard Deviation 30	217 PRU Standard Deviation 36	229 PRU Standard Deviation 34	32 PRU Standard Deviation 53	29 PRU Standard Deviation 57	36 PRU Standard Deviation 61	241 PRU Standard Deviation 38

PRIMARY outcome

Timeframe: 20 days

Comparison of thrombin generation, reported as peak thrombin level measured by a thrombin generation assay, between aspirin plus clopidogrel vs. aspirin plus clopidogrel plus rivaroxaban. This is reflective of the amount of thrombin that is generated following stimuli with tissue factor. The theombin generation assay will be carried out using Technothrombin® fluorogenic assay kit.

Outcome measures

Outcome measures
Measure	Aspirin Plus Clopidogrel n=20 Participants Cohort of patients on aspirin plus clopidogrel	Aspirin Plus Clopidogrel Plus Rivaroxaban n=20 Participants Cohort of patients on aspirin, clopidogrel and rivaroxaban	Clopidogrel Plus Rivaroxaban n=19 Participants Cohort of patients on clopidogrel plus rivaroxaban	Aspirin n=20 Participants Cohort of patients on aspirin only	Aspirin Plus Rivaroxaban n=20 Participants Cohort of patients on aspirin plus rivaroxaban	Rivaroxaban n=19 Participants Cohort of patients on rivaroxaban alone	Aspirin Plus Ticagrelor n=20 Participants Cohort of patients on aspirin plus ticagrelor	Aspirin Plus Ticagrelor Plus Rivaroxaban n=19 Participants Cohort of patients on aspirin plus ticagrelor plus rivaroxaban	Ticagrelor Plus Rivaroxaban n=20 Participants Cohort of patients on ticagrelor plus rivaroxaban	Rivaroxaban 20 mg n=19 Participants Cohort of patients on rivaroxaban 20 mg
Thrombin Generation	235 µM Standard Deviation 57	135 µM Standard Deviation 79	121 µM Standard Deviation 56	248 µM Standard Deviation 77	130 µM Standard Deviation 54	160 µM Standard Deviation 59	263 µM Standard Deviation 66	162 µM Standard Deviation 83	155 µM Standard Deviation 58	103 µM Standard Deviation 85

Adverse Events

Aspirin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Aspirin Plus Clopidogrel

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Aspirin Plus Ticagrelor

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Rivaroxaban

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Aspirin n=20 participants at risk The cohort of patients on aspirin was treated with adjunctive vascular dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy was suspended for 7-10 days.	Aspirin Plus Clopidogrel n=21 participants at risk The cohort of patients on aspirin plus clopidogrel was treated with adjunctive vascular dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy was suspended for 7-10 days.	Aspirin Plus Ticagrelor n=21 participants at risk The cohort of patients on aspirin plus ticagrelor was treated with adjunctive vascular dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy was suspended for 7-10 days.	Rivaroxaban n=20 participants at risk The cohort of patients on rivaroxaban remained on rivaroxaban 20 mg daily.
Blood and lymphatic system disorders Bleeding	0.00% 0/20 • 20 days During study treatment, ischemic cardiac events (including death, myocardial infarction, stroke, or urgent revascularization) and serious adverse events (bleeding and other adverse events) were collected. Given the low number of adverse events (only 1 event occurred), events are reported per cohort. The single event reported occurred in the aspirin plus clopidogrel plus rivaroxaban treatment group.	4.8% 1/21 • 20 days During study treatment, ischemic cardiac events (including death, myocardial infarction, stroke, or urgent revascularization) and serious adverse events (bleeding and other adverse events) were collected. Given the low number of adverse events (only 1 event occurred), events are reported per cohort. The single event reported occurred in the aspirin plus clopidogrel plus rivaroxaban treatment group.	0.00% 0/21 • 20 days During study treatment, ischemic cardiac events (including death, myocardial infarction, stroke, or urgent revascularization) and serious adverse events (bleeding and other adverse events) were collected. Given the low number of adverse events (only 1 event occurred), events are reported per cohort. The single event reported occurred in the aspirin plus clopidogrel plus rivaroxaban treatment group.	0.00% 0/20 • 20 days During study treatment, ischemic cardiac events (including death, myocardial infarction, stroke, or urgent revascularization) and serious adverse events (bleeding and other adverse events) were collected. Given the low number of adverse events (only 1 event occurred), events are reported per cohort. The single event reported occurred in the aspirin plus clopidogrel plus rivaroxaban treatment group.

Additional Information

Dominick Angiolillo, MD,PhD

University of Florida

Phone: 904-244-3378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place