Zibotentan, an Endothelin Receptor Antagonist, Patients With Intermittent Claudication

• Status: Completed
• Trial end date: 2016-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Peripheral artery disease (PAD) is a major complication of atherosclerosis when blockages in the arteries to leg reduce blood flow and one of the resulting problems is termed intermittent claudication (IC). IC is leg pain with walking that is relieved with rest and IC is the most frequent clinical manifestation of PAD and it effects millions of Americans. The number of patients with, and the health care costs of, PAD will increase as the prevalence of PAD is associated with advancing age, diabetes, and smoking. Zibotentan (ZD4054) is an endothelin receptor A (ETA) blocker that undergone extensive human testing and has been shown to be safe in several patient population. There is ample evidence to suggest that an ETA blocker could improve blood flow to the legs in patients with PAD. In a study that will be funded by the National Institute of Health, the investigators will test the ability of this medication to allow better blood flow to the legs of patients with PAD. In patients with IC, the investigators will test the ability of ZD4054 to improve leg blood flow using a non-invasive imaging technique. In parallel the study will test for the ability of patients with leg pain to walk further and feel better.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Virginia
• Collaborator: National Institutes of Health (NIH)
• Treatments: Endothelin Receptor Antagonists

Criteria

Inclusion Criteria:

• Age >40 years. Patients less than 40 years of age could well have a form or "thromboangitis obliterans" often called Berger's Disease and the investigators wish to enroll only subjects with atherosclerotic vascular disease.

• Currently taking all standard medications that are part of the "good medical care" for patients with PAD including an anti-platlet agent, an angiotensin-converting enzyme inhibitors or receptor blockers, beta-blockers if indicated for ischemic heart disease, and cholesterol lowering therapy; unless documented contra-indications to these therapies exist. Those patients not on these therapies will be referred back with the suggestion that they be added and they can be re-approached for enrollment at a later date.

• Exercise induced thigh, calf, buttock pain and absence of Rutherford Class IV, V, or VI.3

• A resting ABI of <0.9 but >0.4 and the presence of both superficial femoral artery stenosis (70% or greater) disease and below the knee disease with a significant stenosis in at least one of the run-off vessels.

• Absence of critical inflow (iliac or common femoral) disease. The profunda femoral artery is the major source of collateral blood vessels. The investigators initial approach will be to try and enroll as homogenous of a patient population as possible to allow us to focus on the primary endpoint of the study (the change in muscle perfusion to the ischemic limb over time).

• Ability to undergo magnetic resonance imaging and provide informed written consent.

Exclusion Criteria:

• Serious known concomitant disease with life expectancy of less than one year

• Prior amputation or history of critical limb ischemia

• Creatinine clearance (CrCl) >45 to permit safe administration of the gadolinium contrast agent.

• Recent myocardial infarction, unstable angina, stroke or transient ischemic attack within 3 months.

• American Heart Association Class III or IV congestive heart failure or known left ventricular ejection fraction less than 40%.

• Known history of anemia