EUCLID to compare ticagrelor with clopidogrel for PAD - AstraZeneca & DCRI

Overview

Status: Active, not recruiting
Keywords: peripheral arterial disease (PAD) , claudication , leg discomfort , painful, aching, cramping, uncomfortable or tired feeling in the legs , bypass leg surgery , Stroke , ticagrelor (Brilinta®) , clopidogrel (Plavix®) , heart problems , 50 years or older
IRB Number: 00061624
Specialty: Vascular Surgery, Geriatrics
Sub Specialties:

Brief Summary

Purpose:

This study will test the hypothesis that ticagrelor monotherapy when compared to clopidogrel monotherapy, will reduce the incidence of the major cardiovascular outcomes in patients with established PAD.

Background:

Recently, data from PLATO, a Phase III study comparing ticagrelor to clopidogrel in ACS patients treated with ASA demonstrated superiority of ticagrelor over clopidogrel in the prevention of fatal and non-fatal cardiovascular (CV) events leading to FDA approval of ticagrelor in patients with ACS.

Population and Study Design:

This is a global multicenter, randomized, double blind clinical trial. Approximately 900 sites will be participating in 25 countries to enroll approximately 13,500 patients. In the U.S, approximately 350 sites will participate.

Subjects with established PAD (as defined by inclusion/exclusion criteria described below) will be given ticagrelor or clopidogrel monotherapy and will be followed for events for 18 – 36 months.

Primary Objective:

The primary objective of the study is to compare the effect of long-term treatment with ticagrelor vs. clopidogrel on the event rate of:

1. CV death

2. Myocardial Infarction

3. Ischemic Stroke.

 

The secondary objectives (presented in hierarchical order) of the study are:

1. Composite of CV death, MI, Ischemic Stroke and Acute Limb Ischemia (ALI)
requiring hospitalization
2. CV death
3. MI
4. All-cause mortality
5. Composite of CV death, MI, and all-cause stroke (ischaemic or haemorrhagic)
6. Acute Limb Ischemia (ALI) requiring hospitalization
7. All Lower Extremity Revascularization
8. All revascularization procedures

 

Duration of Treatment

• Patients will either receive 90 mg ticagrelor orally bd and clopidogrel placebo in the morning, or clopidogrel od (morning) and ticagrelor placebo bd.

• The patients will be followed for an anticipated minimum of 25 months and up to approximately 40 months.  However, the actual duration of the study will be based on accrual of the predetermined number of events (1364) for the primary endpoint, and therefore the study may be shorter or longer than 40 months.

• • The anticipated median duration is 32 months.

 

Detailed Description

Population and Study Design: This is a global multicenter, randomized, double blind clinical trial. Approximately 900 sites will be participating in 25 countries to enroll approximately 11,500 patients. In the U.S, approximately 350 sites will participate. Subjects with established PAD (as defined by inclusion/exclusion criteria described below) will be given ticagrelor or clopidogrel monotherapy and will be followed for events for 18 – 36 months.

Principal Investigator: Larry Kraiss
Department: Vascular Surgery Development
Co Investigator:

Contact Information

Name:Maria Maloney
Phone: 801-585-3663
Email: maria.maloney@hsc.utah.edu

Inclusion Criteria

4.1 Inclusion criteria

To ensure enrolment of patients representative of the PAD disease spectrum, patients will be included based upon objectively verified arterial burden and symptomatic disease. For inclusion in the study patients should fulfil the following criteria at Visit 1.

1. Male and female patients ≥ 50 years of age

2. Symptomatic lower extremity PAD defined by:

Symptoms at the time of screening including classic claudication, other exertional leg discomfort associated with physical limitations from PAD, ischaemic rest pain, ischaemic ulcers, or gangrene

AND

Ankle brachial index (ABI) measurement of ≤ 0.80 at Visit 1. The ABI must be ≤ 0.85 at Visit 2. If ABI is ≥ 1.40 then the toe brachial index (TBI) must be ≤ 0.60 at Visit 1 and the TBI must be ≤ 0.65 at Visit 2.

OR

Prior lower extremity revascularization for symptomatic and haemodynamically significant PAD greater than 30 days prior to randomisation, irrespective of present leg symptoms and the ABI or TBI at the time of study screening

3. Written informed consent prior to any study specific procedures.

Exclusion Criteria

4.2 Exclusion criteria

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

1. Poor metabolizer status for CYP2C19, defined as possessing genotype consisting of 2 loss of function alleles.

2. Hypersensitivity to clopidogrel or ticagrelor

3. Patients requiring dual anti-platelet therapy at study entry

4. Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin or long-term treatment with fondaparinux

5. Planned (and judged necessary) use of ticlopidine, prasugrel, aspirin or dipyridamole

6. Planned (and judged necessary) use of omeprazole or esomeprazole. Note – the use of other proton pump inhibitors is permitted.

7. Any condition which in the opinion of the Investigator would make it unsafe or unsuitable for the patient to participate in this study (eg, active malignancy other than squamous cell or basal cell skin cancer, use of strong or moderate CYP2C19 inhibitors, long-term concomitant treatment with non-steroidal anti-inflammatory drugs [NSAIDs])

8. Life expectancy < 6 months based on investigator’s judgement

9. Planned revascularisation (surgical or endovascular) in any vascular territory within the next 3 months

10. Planned major amputation due to PAD within the next 3 months or major amputation due to PAD within the last 30 days

11. Patients who have suffered a stroke during the past 3 months

12. Dementia likely to jeopardise understanding of information pertinent to study conduct or compliance to study procedures

13. Severe hypertension that may put the patient at risk

14. Patients considered to be at risk of bradycardic events (e.g., known sick sinus syndrome or second or third degree atrioventricular [AV)] block) unless already treated with a permanent pacemaker

15. Known severe liver disease (eg, ascites and/or clinical signs of coagulopathy)

16. Renal failure requiring dialysis

17. A clinically important  bleeding diathesis, haemostatic or coagulation disorder, or systemic bleeding, whether resolved or ongoing

18. History of previous intracranial bleed at any time, gastrointestinal bleed within the past 6 months, or major surgery within 30 days (if the surgical wound is judged to be associated with an increased risk of bleeding)

19.  Clinically important thrombocytopenia or neutropenia

20. Females of child-bearing potential (ie, those who are not chemically or surgically sterilised or who are not post-menopause) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator OR females who have a positive pregnancy test at Visit 1.

21. Concern for inability of the patient to comply with study procedures and/or follow-up (eg, alcohol or drug abuse)

22. Previous randomisation in the present study

23. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study centre)