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Switch to Ticagrelor in Critical Limb Ischemia Anti-platelet Study (STT-CLIPS)

Primary Purpose

Critical Limb Ischemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ticagrelor
Sponsored by
University of Southern California
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional screening trial for Critical Limb Ischemia focused on measuring Critical Limb Ischemia, ticagrelor, Brilinta

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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

Exclusion Criteria:

  • Chronic use of nonsteroidal anti-inflammatory drugs, thrombocytopenia (platelet count <100 × 103/μl), hemoglobin <10 g/dL, use of an oral anticoagulant (warfarin) or low molecular weight heparin within 14 days, GPIIb/IIIa inhibitors, or fibrinolytic drugs within 30 days. Pregnancy, <18 or >80 years of age, current smoking (>1 pack per day), concomitant therapy with strong cytochrome P450 3A inhibitors or inducers within 14 days, concomitant antithrombotic therapy other than aspirin within 14 days, hypercoaguable states. History of medication non-compliance, drug or alcohol abuse within 2 years. Acute coronary syndrome or coronary drug-eluting stenting within 1 year. Peripheral vascular revascularization procedures (surgical or endovascular) and/or amputation within one month. Contraindications for ticagrelor including: hypersensitivity to ticagrelor or any of the excipients, Active pathological bleeding, History of intracranial hemorrhage and Severe hepatic impairment.

Sites / Locations

  • University of Southern California

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental

Arm Description

All subjects will receive Ticagrelor.

Outcomes

Primary Outcome Measures

To Determine Platelet Inhibition Before and After Switching for Two Weeks From Clopidogrel to Ticagrelor in Patients With CLI.
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

Secondary Outcome Measures

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.
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% .
Establish the Number of Participants With Appropriate Platelet Inhibition on Clopidogrel Who Demonstrated Appropriate Platelet Inhibition After Switching to Ticagrelor for Two Weeks.
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
Evaluate the Correlation Between PRU and VASP-PRI in CLI Patients During Clopidogrel Versus Ticagrelor Antiplatelet 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

Full Information

First Posted
March 17, 2014
Last Updated
June 17, 2019
Sponsor
University of Southern California
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1. Study Identification

Unique Protocol Identification Number
NCT02091921
Brief Title
Switch to Ticagrelor in Critical Limb Ischemia Anti-platelet Study
Acronym
STT-CLIPS
Official Title
Switch to Ticagrelor in Critical Limb Ischemia Anti-platelet Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
February 16, 2014 (Actual)
Primary Completion Date
November 30, 2016 (Actual)
Study Completion Date
November 30, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Southern California

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Critical Limb Ischemia (CLI) is defined as limb pain that occurs at rest, or impending limb loss that is caused by severe compromise of blood flow to the affected extremity. CLI is a major cause of death and disability (secondary to myocardial infarction, stroke and amputation). The mortality in patients with CLI approaches 13-25% and 50% at one and five years respectively. High on-treatment platelet reactivity (HPR) in patients treated with aspirin and clopidogrel is associated with increased risk of recurrent cardiovascular events after percutaneous coronary interventions and coronary syndromes. Preliminary studies suggest that the prevalence of HPR in patients with critical limb ischemia treated with aspirin and clopidogrel is as high a 78.5%. In patients with coronary artery disease ticagrelor overcomes non-responsiveness to clopidogrel. However, the antiplatelet effect of ticagrelor in patients with critical limb ischemia is unknown.
Detailed Description
Study Aim: This pilot study aims to investigate platelet function after switching from clopidogrel to ticagrelor in patients with critical limb ischemia. Fifty patients with diagnosis of CLI (Rutherford class IV-VI) treated with clopidogrel 75 mg and aspirin 81 mg daily will be tested for inhibition of platelet aggregation using the VerifyNow P2Y12 and VASP assays before and 6±1 hours after their daily clopidogrel dose. All patients will then be switched from clopidogrel to ticagrelor 90 mg twice daily for two weeks and the VerifyNow and Vasodilator-Stimulated Phosphoprotein (VASP) platelet reactivity assays repeated, samples will be collected before and 6±1 hours after the last ticagrelor dose. For exploratory analysis, patients will be divided in two groups based on the P2Y12 reaction units (PRU): Group 1. High on treatment platelet reactivity on clopidogrel (HPR), defined as P2Y12 reaction units (PRU) ≥208 and Group 2. Appropriate platelet inhibition on clopidogrel (API), defined as P2Y12 reaction units (PRU) <208. If subjects are withdrawn from the study prior to completion due to the high co-morbidity rate of this population, additional subjects will be enrolled to reach a total of 50 completed subjects for data analysis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Critical Limb Ischemia
Keywords
Critical Limb Ischemia, ticagrelor, Brilinta

7. Study Design

Primary Purpose
Screening
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Experimental
Arm Type
Experimental
Arm Description
All subjects will receive Ticagrelor.
Intervention Type
Drug
Intervention Name(s)
Ticagrelor
Other Intervention Name(s)
Brilinta
Intervention Description
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.
Primary Outcome Measure Information:
Title
To Determine Platelet Inhibition Before and After Switching for Two Weeks From Clopidogrel to Ticagrelor in Patients With CLI.
Description
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
Time Frame
Two weeks
Secondary Outcome Measure Information:
Title
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.
Description
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% .
Time Frame
Two weeks
Title
Establish the Number of Participants With Appropriate Platelet Inhibition on Clopidogrel Who Demonstrated Appropriate Platelet Inhibition After Switching to Ticagrelor for Two Weeks.
Description
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
Time Frame
Two weeks
Title
Evaluate the Correlation Between PRU and VASP-PRI in CLI Patients During Clopidogrel Versus Ticagrelor Antiplatelet Therapy.
Description
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
Time Frame
Two weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Patients with diagnosis of CLI (Rutherford class IV, V and VI) on continuous dual antiplatelet therapy with aspirin 81 mg and clopidogrel 75 mg daily for at least 14+2 days . Exclusion Criteria: Chronic use of nonsteroidal anti-inflammatory drugs, thrombocytopenia (platelet count <100 × 103/μl), hemoglobin <10 g/dL, use of an oral anticoagulant (warfarin) or low molecular weight heparin within 14 days, GPIIb/IIIa inhibitors, or fibrinolytic drugs within 30 days. Pregnancy, <18 or >80 years of age, current smoking (>1 pack per day), concomitant therapy with strong cytochrome P450 3A inhibitors or inducers within 14 days, concomitant antithrombotic therapy other than aspirin within 14 days, hypercoaguable states. History of medication non-compliance, drug or alcohol abuse within 2 years. Acute coronary syndrome or coronary drug-eluting stenting within 1 year. Peripheral vascular revascularization procedures (surgical or endovascular) and/or amputation within one month. Contraindications for ticagrelor including: hypersensitivity to ticagrelor or any of the excipients, Active pathological bleeding, History of intracranial hemorrhage and Severe hepatic impairment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leonardo Clavijo, MD, PhD
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Switch to Ticagrelor in Critical Limb Ischemia Anti-platelet Study

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