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
Overview
- Phase
- Phase 4
- Intervention
- Ticagrelor
- Conditions
- Peripheral Artery Disease
- Sponsor
- AstraZeneca
- Primary Endpoint
- Assessment of ticagrelor when compared to clopidogrel on adenosine-induced myocardial blood flow (MBF) by cardiac 13N ammonia Positron EmissionTomography (PET) at Visit 2
- Status
- Withdrawn
- Last Updated
- 11 years ago
Overview
Brief Summary
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).
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.
Investigators
Eligibility Criteria
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.
- •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.
Arms & Interventions
Ticagrelor
oral ticagrelor 90 mg (yellow) tablet
Intervention: Ticagrelor
Clopidogrel
oral clopidogrel 75 mg (pink) tablet
Intervention: clopidogrel
Outcomes
Primary Outcomes
Assessment of ticagrelor when compared to clopidogrel on adenosine-induced myocardial blood flow (MBF) by cardiac 13N ammonia Positron EmissionTomography (PET) at Visit 2
Time Frame: Visit 2 (Day 1): 1 day treament visit
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.
Secondary Outcomes
- Assessment of ticagrelor when compared to clopidogrel on adenosine-induced myocardial blood flow (MBF) by cardiac 13N ammonia Positron EmissionTomography (PET) at Vist 3(Visit 3 (Day 7): occurs 7 days after Visit 2)