Peripheral Arterial DiseasePhase 2NCT01890135
Zibotentan, an Endothelin Receptor Antagonist, Patients With Intermittent Claudication
A Phase 2 study testing Zibotentan (ZD4054) in people with Peripheral Arterial Disease and Intermittent Claudication, run by University of Virginia at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Peripheral Arterial Disease, Intermittent Claudication
- What is being tested?
- Zibotentan (ZD4054)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to Jun 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University Of Virginia Health System
Charlottesville, Virginia, 22908
About this study
Official title: A Phase II Clinical Trail to Assess the Safety and Effects of ZD4054 (Zibotentan) on Exercise Induced Calf Muscle Perfusion in Patients With Intermittent Claudication (Rutherford II or III).
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.
Read the detailed description
Peripheral artery disease (PAD) is a major complication of atherosclerosis that affects >8 million people in the United States alone. Intermittent claudication (IC), defined as leg pain with walking that is relieved with rest, is the most frequent clinical manifestation of PAD.
In a proposal that was just funded by the National Institute of Health (NIH) National Center for Advancing TRanslational Sciences (NCATS) the investigators pose to test the "reuse" of zibotentan (ZD4054, an Asta-Zeneca compound), an orally active, endothelin receptor A (ETA) antagonist in patients with IC. The study will seek to confirm the safety and tolerability of 10mg of ZD4054 in patients with intermittent claudication (Rutherford II or III) and, in parallel, establish the capacity of ZD4054 to change calf muscle perfusion, as assessed by contrast-enhanced magnetic resonance imaging, functional treadmill performance, and quality of life indicators.
The study will be a 1:1 randomized, double-blind, placebo-controlled trial of 44 subjects with intermittent claudication with randomization stratified based on the entry calf muscle perfusion. The investigators will use magnetic resonance imaging to quantify changes in blood flow to the ischemic limb from baseline to week 12 between those randomized to drug vs. placebo. Based on the prior experience and the known tolerability of ZD4054, the experience of the investigative team with a mechanistically appropriate end-point measure that is part of other NIH funded projects, the investigators will proceed directly to this Phase II trial. The primary endpoint of the study will be the change in absolute perfusion in the index calf muscle from baseline to follow-up, after 12 weeks on the 10 mg dose or placebo. Additional outcome measures will be: a) ability of patients with PAD to tolerate 10 mg dose of ZD4054 vs. placebo; b) freedom from unexpected serious adverse events; c) change in peak walking time from baseline to 12 weeks between 10 mg of ZD4054 and placebo groups; d) change in ankle-brachial blood pressure index (ABI) from baseline to 12 weeks between 10 mg of ZD4054 and placebo groups, and; d) change in quality of life measure between 10 mg of ZD4054 and placebo groups.
- Being tested
- Zibotentan (ZD4054), placebo
- Keywords
- randomized, double blind, blood flow, muscle perfusion, safety
- Medical subject headings
- Peripheral Arterial Disease, Intermittent Claudication
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zibotentan (ZD4054)Drug
10 mg
placeboDrug
Also called matched placebo
randomized double blind
| Study group | Role | What they receive |
|---|---|---|
| endothelin receptor antogonist | Active comparator | 10 mg of zibotentan Receives: Drug: Zibotentan (ZD4054); Drug: placebo |
| placebo | Placebo comparator | matched placebo Receives: Drug: Zibotentan (ZD4054); Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in exercise-induced calf muscle perfusion by magnetic resonance imaging
Measured: Baseline and 12 weeks
Secondary outcomes (3)
Change in peak walking time
Peak walking time (PWT) will be measured using the Gardner treadmill protocol which is designed for patients with peripheral arterial disease.
Measured: Baseline and 12 weeks
Change in quality of life measures
Quality of life measures specific to peripheral arterial disease will be assessed by questionnaire.
Measured: Baseline and 12 weeks
Safety
Confirmation of lack of change in edema or heart failure by history and physical examination
Measured: Baseline and Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2013 (estimated)
- Study startJun 2013
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Brian Annex, MD, University of Virginia
- Investigators
- Brian H Annex, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01890135
- Sponsor's protocol ID
- 17030
- Status last verified
- Aug 2016
- First submitted
- 18 Jun 2013
- Last updated
- 2 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trail to Assess the Safety and Effects of ZD4054 (Zibotentan) on Exercise Induced Calf Muscle Perfusion in Patients With Intermittent Claudication (Rutherford II or III).
- ClinicalTrials.gov ID
- NCT01890135
- Acronym / sponsor ID
- 17030
- Keywords
- randomized, double blind, blood flow, muscle perfusion, safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Jun 2013
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 1 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Peripheral artery disease (PAD) is a major complication of atherosclerosis that affects >8 million people in the United States alone. Intermittent claudication (IC), defined as leg pain with walking that is relieved with rest, is the most frequent clinical manifestation of PAD.
In a proposal that was just funded by the National Institute of Health (NIH) National Center for Advancing TRanslational Sciences (NCATS) the investigators pose to test the "reuse" of zibotentan (ZD4054, an Asta-Zeneca compound), an orally active, endothelin receptor A (ETA) antagonist in patients with IC. The study will seek to confirm the safety and tolerability of 10mg of ZD4054 in patients with intermittent claudication (Rutherford II or III) and, in parallel, establish the capacity of ZD4054 to change calf muscle perfusion, as assessed by contrast-enhanced magnetic resonance imaging, functional treadmill performance, and quality of life indicators.
The study will be a 1:1 randomized, double-blind, placebo-controlled trial of 44 subjects with intermittent claudication with randomization stratified based on the entry calf muscle perfusion. The investigators will use magnetic resonance imaging to quantify changes in blood flow to the ischemic limb from baseline to week 12 between those randomized to drug vs. placebo. Based on the prior experience and the known tolerability of ZD4054, the experience of the investigative team with a mechanistically appropriate end-point measure that is part of other NIH funded projects, the investigators will proceed directly to this Phase II trial. The primary endpoint of the study will be the change in absolute perfusion in the index calf muscle from baseline to follow-up, after 12 weeks on the 10 mg dose or placebo. Additional outcome measures will be: a) ability of patients with PAD to tolerate 10 mg dose of ZD4054 vs. placebo; b) freedom from unexpected serious adverse events; c) change in peak walking time from baseline to 12 weeks between 10 mg of ZD4054 and placebo groups; d) change in ankle-brachial blood pressure index (ABI) from baseline to 12 weeks between 10 mg of ZD4054 and placebo groups, and; d) change in quality of life measure between 10 mg of ZD4054 and placebo groups.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| endothelin receptor antogonist | Active comparator | Drug: Zibotentan (ZD4054), Drug: placebo10 mg of zibotentan |
| placebo | Placebo comparator | Drug: Zibotentan (ZD4054), Drug: placebomatched placebo |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (6 listed)
- 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%.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zibotentan (ZD4054)10 mg | Drug | endothelin receptor antogonist, placebo |
| placeboAlso: matched placeborandomized double blind | Drug | endothelin receptor antogonist, placebo |
Primary outcome
Change in exercise-induced calf muscle perfusion by magnetic resonance imaging
Time frame: Baseline and 12 weeks
3 secondary outcomes
Change in peak walking time
Time frame: Baseline and 12 weeks
Change in quality of life measures
Time frame: Baseline and 12 weeks
Safety
Time frame: Baseline and Day 30
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian H Annex, MD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zibotentan (ZD4054) in people with Peripheral Arterial Disease and Intermittent Claudication, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in exercise-induced calf muscle perfusion by magnetic resonance imaging (time frame: Baseline and 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2016.