Trial Outcomes & Findings for Switch to Ticagrelor in Critical Limb Ischemia Anti-platelet Study (NCT NCT02091921)

NCT ID: NCT02091921

Last Updated: 2019-06-19

Results Overview

Patients platelet inhibition was analyzed based on the P2Y12 reaction units (PRU) as high on treatment platelet reactivity (HPR), defined as P2Y12 reaction units (PRU) ≥208 and appropriate platelet inhibition on (API), defined as P2Y12 reaction units (PRU) \<208

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 53 participants
• Primary outcome timeframe: Two weeks
• Results posted on: 2019-06-19

Participant Flow

Patients with diagnosis of CLI (Rutherford class IV, V and VI) on continuous dual antiplatelet therapy with clopidogrel 75 mg and aspirin 81 mg daily for at least 14+2 days

A total of 53 patients consented and enrolled the study. 3 patients were excluded from the study and did not complete the study; one developed a skin reaction after the first IP dose; the other two due to events unrelated to the study (Pneumonia and Rheumatoid arthritis pericarditis). 50 Patients completed the study.

Participant milestones

Measure	Experimental All subjects will receive Ticagrelor. Ticagrelor: All patients will be switched from clopidogrel to ticagrelor 90 mg twice daily for two weeks and the VerifyNow and VASP platelet reactivity assays repeated, samples will be collected before and 6±1 hours after the last ticagrelor dose.
Overall Study STARTED	53
Overall Study COMPLETED	50
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Experimental All subjects will receive Ticagrelor. Ticagrelor: All patients will be switched from clopidogrel to ticagrelor 90 mg twice daily for two weeks and the VerifyNow and VASP platelet reactivity assays repeated, samples will be collected before and 6±1 hours after the last ticagrelor dose.
Overall Study Adverse Event	3

Baseline Characteristics

Switch to Ticagrelor in Critical Limb Ischemia Anti-platelet Study

Baseline characteristics by cohort

Measure	Experimental n=50 blood samples All subjects will receive Ticagrelor. Ticagrelor: All patients will be switched from clopidogrel to ticagrelor 90 mg twice daily for two weeks and the VerifyNow and VASP platelet reactivity assays repeated, samples will be collected before and 6±1 hours after the last ticagrelor dose.
Age, Continuous	65.3 years STANDARD_DEVIATION 10.6 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants
Region of Enrollment United States	50 Participants n=5 Participants

PRIMARY outcome

Timeframe: Two weeks

Patients platelet inhibition was analyzed based on the P2Y12 reaction units (PRU) as high on treatment platelet reactivity (HPR), defined as P2Y12 reaction units (PRU) ≥208 and appropriate platelet inhibition on (API), defined as P2Y12 reaction units (PRU) <208

Outcome measures

Measure	Ticagrelor n=50 Participants All patients were switched from clopidogrel to ticagrelor 90 mg twice daily for two weeks
To Determine Platelet Inhibition Before and After Switching for Two Weeks From Clopidogrel to Ticagrelor in Patients With CLI. Clopidogrel Baseline	173 P2Y12 reaction units (PRU) Interval 149.0 to 196.0
To Determine Platelet Inhibition Before and After Switching for Two Weeks From Clopidogrel to Ticagrelor in Patients With CLI. Clopidogrel 6+-1 hour after the baseline dose	140 P2Y12 reaction units (PRU) Interval 116.0 to 163.0
To Determine Platelet Inhibition Before and After Switching for Two Weeks From Clopidogrel to Ticagrelor in Patients With CLI. Ticagrelor Baseline	71 P2Y12 reaction units (PRU) Interval 47.0 to 94.0
To Determine Platelet Inhibition Before and After Switching for Two Weeks From Clopidogrel to Ticagrelor in Patients With CLI. Ticagrelor 6+-1 hour after baseline	63 P2Y12 reaction units (PRU) Interval 39.0 to 86.0

SECONDARY outcome

Timeframe: Two weeks

Population: Participants who demonstrated on the High Platelet Reactivity (HPR) on clopidogrel and had Appropriate Platelet Inhibition (API) on ticagrelor

This measure was obtained by the number of participants who demonstrated high on treatment platelet reactivity (PRU > / = 208) on Clopidogrel, and the number of participants who also resulted in the Appropriate Platelet Inhibition (PRU < 208) after switching to Ticagrelor for two weeks of uninterrupted therapy x 100% .

Outcome measures

Measure	Ticagrelor n=18 Participants All patients were switched from clopidogrel to ticagrelor 90 mg twice daily for two weeks
Establish the Number of Participants in the High On-treatment Platelet Reactivity (HPR) on Clopidogrel Group Who Demonstrated Appropriate Platelet Inhibition (API) After Switching to Ticagrelor for Two Weeks.	17 Participants

SECONDARY outcome

Timeframe: Two weeks

Population: Participants who demonstrated API on Clopidogrel and remained with API after switching to Ticagrelor

The measure was obtained from the number of participants in the Appropriate Platelet Inhibition (PRU < 208) on Clopidogrel and who remained with Appropriate Platelet Inhibition after switching to Ticagrelor for two weeks of uninterrupted therapy x 100

Outcome measures

Measure	Ticagrelor n=32 Participants All patients were switched from clopidogrel to ticagrelor 90 mg twice daily for two weeks
Establish the Number of Participants With Appropriate Platelet Inhibition on Clopidogrel Who Demonstrated Appropriate Platelet Inhibition After Switching to Ticagrelor for Two Weeks.	32 Participants

SECONDARY outcome

Timeframe: Two weeks

Population: All participants were on Clopidogrel 75mg daily for at least two weeks and then switched to Ticagrelor 90mg twice daily for two weeks of uninterrupted therapy

Correlation between the P2Y12 Reaction Units (PRU) and the Vasodilator-Stimulated Phosphoprotein Assay-Platelet Reactivity Index (VASP-PRI) used to test the inhibition of platelet aggregation after two weeks of uninterrupted therapy with Clopidogrel versus Ticagrelor in CLI participants

Outcome measures

Measure	Ticagrelor n=200 Correlation Coefficient All patients were switched from clopidogrel to ticagrelor 90 mg twice daily for two weeks
Evaluate the Correlation Between PRU and VASP-PRI in CLI Patients During Clopidogrel Versus Ticagrelor Antiplatelet Therapy. Clopidogrel	0.73 Correlation Coefficient
Evaluate the Correlation Between PRU and VASP-PRI in CLI Patients During Clopidogrel Versus Ticagrelor Antiplatelet Therapy. Ticagrelor	0.47 Correlation Coefficient
Evaluate the Correlation Between PRU and VASP-PRI in CLI Patients During Clopidogrel Versus Ticagrelor Antiplatelet Therapy. Overall Group	0.6 Correlation Coefficient

Adverse Events

Experimental

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Experimental n=53 participants at risk All participants will switch from clopidogrel to ticagrelor for two weeks
Respiratory, thoracic and mediastinal disorders Hospitalization for Pneumonia	1.9% 1/53 • Number of events 1 • Two weeks The adverse event and/or serious adverse event, used to collect adverse event information, adheres to the clinicaltrials.gov definition
Immune system disorders Rheumatoid arthritis pericarditis	1.9% 1/53 • Number of events 1 • Two weeks The adverse event and/or serious adverse event, used to collect adverse event information, adheres to the clinicaltrials.gov definition

Other adverse events

Measure	Experimental n=53 participants at risk All participants will switch from clopidogrel to ticagrelor for two weeks
Skin and subcutaneous tissue disorders Skin reaction	1.9% 1/53 • Number of events 1 • Two weeks The adverse event and/or serious adverse event, used to collect adverse event information, adheres to the clinicaltrials.gov definition

Additional Information

Leonardo Clavijo, MD

University of Southern California

Phone: 3234426130

Email: lclavijo@usc.edu

Results disclosure agreements

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