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

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ClinicalTrials.gov Identifier: NCT02091921
Recruitment Status : Completed
First Posted : March 19, 2014
Results First Posted : June 19, 2019
Last Update Posted : June 19, 2019
Sponsor:
Information provided by (Responsible Party):
Leonardo Clavijo, University of Southern California

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.

Condition or disease Intervention/treatment Phase
Critical Limb Ischemia Drug: Ticagrelor Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Switch to Ticagrelor in Critical Limb Ischemia Anti-platelet Study
Actual Study Start Date : February 16, 2014
Actual Primary Completion Date : November 30, 2016
Actual Study Completion Date : November 30, 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Ticagrelor

Arm Intervention/treatment
Experimental: Experimental
All subjects will receive Ticagrelor.
Drug: 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.
Other Name: Brilinta




Primary Outcome Measures :
  1. To Determine Platelet Inhibition Before and After Switching for Two Weeks From Clopidogrel to Ticagrelor in Patients With CLI. [ Time Frame: 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


Secondary Outcome Measures :
  1. 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. [ Time Frame: 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% .

  2. Establish the Number of Participants With Appropriate Platelet Inhibition on Clopidogrel Who Demonstrated Appropriate Platelet Inhibition After Switching to Ticagrelor for Two Weeks. [ Time Frame: 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

  3. Evaluate the Correlation Between PRU and VASP-PRI in CLI Patients During Clopidogrel Versus Ticagrelor Antiplatelet Therapy. [ Time Frame: Two weeks ]
    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



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02091921


Locations
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United States, California
University of Southern California
Los Angeles, California, United States, 90033
Sponsors and Collaborators
University of Southern California
Investigators
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Principal Investigator: Leonardo Clavijo, MD, PhD University of Southern California

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Responsible Party: Leonardo Clavijo, Principal Investigator, Director, University of Southern California
ClinicalTrials.gov Identifier: NCT02091921     History of Changes
Other Study ID Numbers: D5130L00068//ISSBRIL0198
HS-13-00562 ( Other Identifier: IRB )
First Posted: March 19, 2014    Key Record Dates
Results First Posted: June 19, 2019
Last Update Posted: June 19, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Leonardo Clavijo, University of Southern California:
Critical Limb Ischemia, ticagrelor, Brilinta

Additional relevant MeSH terms:
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Ischemia
Pathologic Processes
Ticagrelor
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs