Adenosine-induced Myocardial Blood Flow in Peripheral Artery Disease Patients (PAD)

A Randomized, Open-Label, Parallel, Multi-Center, Phase IV Study to Assess the Effect of Ticagrelor vs Clopidogrel on Adenosine-Induced Myocardial Blood Flow in Peripheral Artery Disease (PAD)Patients

The purpose of the study is to assess the effect of blood flow to the heart when subjects are treated with ticagrelor (Brilinta) or clopidogrel (antiplatelet drugs that stop the blood from clumping together) in patients with Peripheral Artery Disease (PAD).

Study Overview

• Status: Withdrawn
• Conditions: Intermittent Claudication; Peripheral Artery Disease; Vascular Disease; Arterial Occlusion Disease; Ankle Brachial Index (0.9 or Less)
• Intervention / Treatment: Drug: Ticagrelor; Drug: clopidogrel

Detailed Description

The effects of ticagrelor and clopidogrel on adenosine-induced myocardial blood flow (MBF) will be evaluated by cardiac 13N- ammonia positron emission tomography (PET) at rest (baseline), acute dosing on Day 1, and at short term dosing on Day 7.

Subjects receiving ticagrelor will have additional pharmacokinetic (PK) blood samples collected at specific time points to measure ticagrelor concentration in the blood. Subjects' participation will be approximatetly 6 weeks.

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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, AND Ankle brachial index (ABI) measurement at Visit 1 needs to be < 0.90. 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 Ankle Brachial Index (ABI).
• Male and female ≥ 18 years of age and less than 60 yrs.
• Subjects must be taking clopidogrel (75mg/day) for at least 30 days prior to entry to study.

Exclusion Criteria:

• Participation in another clinical study with an investigational product during the last 30 days.
• History of ACS within the last 1 year.
• Hypersensitivity or contraindications to clopidogrel or ticagrelor.
• Need for chronic oral anticoagulant therapy or chronic low- molecular-weight heparin or long-term treatment with fondaparinux, warfarin, apixaban, rivoroxaban, and parenteral anticoagulants such as enoxeparin, and bivalirudin.
• Life expectancy < 6 months based on investigator's judgment.
• Planned lower extremity revascularization (surgical or endovascular) in any vascular territory within the next 3 months or with current ischemic ulcers or gangrene.
• Planned major amputation due to PAD within the next 3 months or major amputation due to PAD within the last 30 days.
• Subjects who have suffered a stroke during the past 3 months.
• Dementia likely to jeopardize understanding of information pertinent to study conduct or compliance to study procedures
• Severe hypertension that may put the subject at risk.
• Subjects considered to be at risk of bradycardic events (e.g., known sick sinus syndrome or second or third degree AV block unless already treated with a permanent pacemaker.
• Known severe liver disease (e.g., ascites and/or clinical signs of coagulopathy).
• Renal failure requiring dialysis
• A known bleeding diathesis, haemostatic or coagulation disorder, or systemic bleeding, whether resolved or ongoing
• 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).
• History of thrombocytopenia or neutropenia
• Females of child-bearing potential (i.e., those who are not chemically or surgically sterilized, post-menopausal who are not willing to use an accepted method of treatment OR who have a positive pregnancy test at screening.
• Concern for inability of the subject to comply with study procedures and/or follow-up (e.g., alcohol or drug abuse).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ticagrelor; oral ticagrelor 90 mg (yellow) tablet	Drug: Ticagrelor; Day 1: Loading dose of ticagrelor 180mg (two 90mg tablets) followed by 90mg dose at 12 hours after loading dose. Subject continues to take ticagrelor 90mg twice a day (morning and evening) for 7 days until next visit (Day 7).; Other Names: Brilinta
Active Comparator: Clopidogrel; oral clopidogrel 75 mg (pink) tablet	Drug: clopidogrel; Day 1: Clopidogrel 75mg oral tablet. Subjects will continue to take clopidogrel 75mg once a day for 7 days until next visit (Day 7/Visit 3). Note: no loading dose is given for the clopidogrel as those subjects are already on chronic dosing.; Other Names: Plavix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of ticagrelor when compared to clopidogrel on adenosine-induced myocardial blood flow (MBF) by cardiac 13N ammonia Positron EmissionTomography (PET) at Visit 2	Assess the acute treatment effects on the 13N-ammonia PET measure and evaulate if they can be correlated with plasma exposure of ticagrelor and or its active metabolite. Subjects will recieve 180mg ticagrelor loading dose or no loading dose for clopidogrel arm, since those subjects are already on chronic dosing. Subjects will undergo additional adenosine-PET at 2 hours following ticagrelor or 4 hours following clopidogrel administration to ascertain MBF.	Visit 2 (Day 1): 1 day treament visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of ticagrelor when compared to clopidogrel on adenosine-induced myocardial blood flow (MBF) by cardiac 13N ammonia Positron EmissionTomography (PET) at Vist 3	Assess the short-term treatment effects on the 13N-ammonia PET measure and evaulate if they can be correlated with plasma exposure of ticagrelor and or its active metabolite. The same sequence described at Visit 2 will be repeated during Visit 3.	Visit 3 (Day 7): occurs 7 days after Visit 2

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Gabriel Vorobiof, MD, UCLA David Geffen School of Medicine

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Anticipated): February 1, 2016
• Study Completion (Anticipated): February 1, 2016

Study Registration Dates

• First Submitted: April 22, 2014
• First Submitted That Met QC Criteria: April 22, 2014
• First Posted (Estimate): April 23, 2014

Study Record Updates

• Last Update Posted (Estimate): October 15, 2014
• Last Update Submitted That Met QC Criteria: October 14, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Peripheral Artery Disease; Myocardial Blood Flow; Cardiac Blood Flow
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Vascular Diseases; Vascular Diseases; Peripheral Arterial Disease; Intermittent Claudication; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel
• Other Study ID Numbers: D5135L00001