Peripheral Arterial DiseasePhase 4Evol-PADNCT04306081
Effect of Evolocumab in Functional Status and LDL Oxidation of Patients With Peripheral Arterial Disease
A Phase 4 study testing Evolocumab 140 mg/mL Subcutaneous Injection 1 milliliter (mL) pre-filled injector Pen x 3 for a monthly dose of 420 mg for 6 months. in people with Peripheral Arterial Disease, run by Leonardo Clavijo at 1 site in United States.
Trial summary
Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerotic cardiovascular disease (ASCVD) and is associated with increase cardiovascular risk. PAD impairs quality of life due to symptoms of claudication, pain at rest or risk of limb loss. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Peripheral Arterial Disease
- What is being tested?
- Evolocumab 140 mg/mL Subcutaneous Injection 1 milliliter (mL) pre-filled injector Pen x 3 for a monthly dose of 420 mg for 6 months.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Dec 2017to 30 Mar 2021
- Phase
- Phase 4
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent.
- Age ≥40 to ≤85 years of age at the time of consent.
- Diagnosis of ASCVD with peripheral arterial disease, Rutherford class I-VI at the time of diagnosis, confirmed by ABI≤0.9 at rest or ABI≤0.8 after exercise, angiography, duplex ultrasound or history of lower extremity surgical or endovascular revascularization.
- At least 1 months from last intervention, including surgery or endovascular procedures.
- Stable on maximal tolerated doses of a lipid-lowering regimen for at least 4 weeks.
- Most recent fasting LDL-C ≥55 mg/dL or non-HDL-C ≥80 mg/dL.
Who cannot join
- Subjects with active, non-healed wounds.
- Subjects with anticipated need of cardiac or surgical revascularization procedures.
- Subjects with chronic inflammatory conditions or requiring chronic systemic corticosteroids.
- New York Heart Association (NYHA) class III or IV heart failure, or known left ventricular ejection fraction <30%.
- Uncontrolled arrhythmia.
- Uncontrolled hypertension with systolic BP>180 mmHg or diastolic >100 mmHg.
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- Untreated thyroid disease.
- Severe chronic renal disease with estimated glomerular filtration rate (eGFR) <20 mL/min.
- Liver disease with aspartame aminotransferase (AST) or alanine aminotransferase (ALT) ≥3 times the upper limit of normal.
- Status post-organ transplant.
- Pregnant and breastfeeding women
- Fertile age female not on appropriate birth control.
- Clinically significant disease that, in the opinion of the Principal Investigator, is likely to require surgery or immunotherapy that may interfere with the completion of the study.
- Active cancer or life expectancy of less than two years.
- Chronic anticoagulation or hypercoagulability disorder.
- Atrial fibrillation with a CHADS-VASc Score ≥2 or any clinical condition which, in the opinion of the Principal Investigator increases the risk of cerebrovascular events.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
University of Southern California
Los Angeles, California, 90033
Jorge Caro, MPH, 323-382-7646, Jorge.Caro@med.usc.edu
Melissa Ramos, RN, 323-442-7983, Melissa.Ramos@med.usc.edu
About this study
Official title: Effect of Evolocumab in Functional Status and LDL Oxidation of Patients With Peripheral Arterial Disease (Evol-PAD)
Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerotic cardiovascular disease (ASCVD) and is associated with increase cardiovascular risk. PAD impairs quality of life due to symptoms of claudication, pain at rest or risk of limb loss.
All major societies recognize the importance of LDL reduction in patients with PAD.
Read more
Statin therapy improves cardiovascular end-points in patients with PAD and have been shown to improve symptoms of lower extremity intermittent claudication (pain free walking time), 6-minute walking time, ankle-brachial index (ABI), and endothelial function, while decreasing markers of atherosclerosis.
This study aims to demonstrate that in patients with PAD on stable maximal tolerated lipid lowering regimen with a statin, further reduction of LDL with the pro protein converts subtilisin/kexin type 9 (PCSK-9) inhibitor Evolocumab, improves functional status (pain free walking time in particular, but also maximal walking time), lower extremity arterial perfusion and endothelial function (brachial endothelial reactivity).
Read the detailed description
This is a double-blinded, prospective, randomized, study in eighty-six subjects with clinical ASCVD with PAD on background treatment with maximal tolerated dose of a statin. Subjects will be assessed based on their medical history and physical examination. Eligible subjects must meet all inclusion criteria and none of the exclusion criteria (listed below). There will be a treatment group and a placebo group, each with equal number of participants (n=43 patients in each group). After consent and enrollment, subjects will have a venous blood sample drawn to perform serum circulating biomarkers of oxidative stress as oxidized low density lipoprotein (oxLDL), oxidized glutathione : reduced glutathione (GSH:GSSG) and soluble CD36 (sCD36). We will then perform: functional walking measurements, pain free walking time (PFWT), and (maximal walking time (MWT), lower extremity arterial perfusion assessment (rest ABI/TBI, post-exercise ABI and bilateral TcPO2), and brachial endothelial function testing (after hyperemia). Subjects will receive monthly subcutaneous injections of Evolocumab 420 mg or placebo injection. The study participants will be seen at three months and six months for follow up and a final assessment at 26 +/-2 weeks, all tests will be repeated for comparison from baseline and/or placebo.
- Conditions
- Peripheral Arterial Disease
- Being tested
- Evolocumab 140 mg/mL Subcutaneous Injection 1 milliliter (mL) pre-filled injector Pen x 3 for a monthly dose of 420 mg for 6 months., Placebo 1milliliter (mL) Subcutaneous Injection pre-filled injector Pen x 3 monthly for 6 months.
- Keywords
- PAD, Hyperlipidemia, Claudication
- Medical subject headings
- Peripheral Arterial Disease, Hyperlipidemias, Intermittent Claudication
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Evolocumab 140 mg/mL Subcutaneous Injection 1 milliliter (mL) pre-filled injector Pen x 3 for a monthly dose of 420 mg for 6 months.Drug
Also called Repatha
The study subjects randomized to the treatment study arm will receive monthly subcutaneous injections of evolocumab 420 mg in the abdomen, thigh or upper arm. The study drug (evolocumab) prefilled injector pens are provided by Amgen
Placebo 1milliliter (mL) Subcutaneous Injection pre-filled injector Pen x 3 monthly for 6 months.Other
Also called Control
The study subjects randomized to the treatment study arm will receive monthly subcutaneous injections of Placebo in the abdomen, thigh or upper arm. The Placebo prefilled injector pens are provided by Amgen
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | 43 Patients with lower extremities Peripheral Arterial Disease on maximum statin therapy will receive in addition a monthly dose of evolocumab 420 mg via subcutaneous injections for 6 months. Receives: Drug: Evolocumab 140 mg/mL Subcutaneous Injection 1 milliliter (mL) pre-filled injector Pen x 3 for a monthly dose of 420 mg for 6 months. |
| Control Arm | Placebo comparator | 43 Patients with lower extremities Peripheral Arterial Disease on maximum statin therapy will receive in addition a monthly dose of placebo via subcutaneous injections for 6 months. Receives: Other: Placebo 1milliliter (mL) Subcutaneous Injection pre-filled injector Pen x 3 monthly for 6 months. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evolocumab effect in pain free walking time (PFWT) in patients with PAD
To evaluate change in pain free walking time (PFWT) in patients with PAD at baseline and after six months of therapy with Evolocumab.
PFWT will be measured in minutes, using a graded treadmill Gardner protocol with a constant speed of 2 miles per hour, increasing by 2% grade every 2 minutes.
Measured: six months
Secondary outcomes (1)
Evolocumab effect in maximal walking time (MWT) in patients with PAD
To evaluate changes in maximal walking time (MWT) in patients with PAD at baseline and after six months of therapy with Evolocumab.
MWT will be measured in minutes, using a graded treadmill Gardner protocol with a constant speed of 2 miles per hour, increasing by 2% grade every 2 minutes.
Measured: six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2020
- Study start14 Dec 2017
- Primary completion30 Dec 2020 (estimated)
- Study completion30 Mar 2021 (estimated)
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.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a double-blinded, prospective, randomized, placebo-controlled study.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 86 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leonardo Clavijo
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor-investigator, Leonardo Clavijo, University of Southern California
- Investigators
- Leonardo Clavijo, MD, PhD, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04306081
- Sponsor's protocol ID
- 20167764
- Other IDs
- HS-16-00965
- Acronym
- Evol-PAD
- Status last verified
- Mar 2020
- First submitted
- 21 Feb 2020
- Last updated
- 12 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Evolocumab in Functional Status and LDL Oxidation of Patients With Peripheral Arterial Disease (Evol-PAD)
- ClinicalTrials.gov ID
- NCT04306081
- Acronym / sponsor ID
- Evol-PAD / 20167764
- Conditions
- Peripheral Arterial Disease
- Keywords
- PAD, Hyperlipidemia, Claudication
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 86 participants (estimated)
- Lead sponsor
- Leonardo ClavijoUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 14 Dec 2017 (actual)
- Primary completion
- 30 Dec 2020 (estimated)
- Study completion
- 30 Mar 2021 (estimated)
- First posted
- 12 Mar 2020 (actual)
- 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 arterial disease (PAD) is a manifestation of systemic atherosclerotic cardiovascular disease (ASCVD) and is associated with increase cardiovascular risk. PAD impairs quality of life due to symptoms of claudication, pain at rest or risk of limb loss.
All major societies recognize the importance of LDL reduction in patients with PAD.
Statin therapy improves cardiovascular end-points in patients with PAD and have been shown to improve symptoms of lower extremity intermittent claudication (pain free walking time), 6-minute walking time, ankle-brachial index (ABI), and endothelial function, while decreasing markers of atherosclerosis.
This study aims to demonstrate that in patients with PAD on stable maximal tolerated lipid lowering regimen with a statin, further reduction of LDL with the pro protein converts subtilisin/kexin type 9 (PCSK-9) inhibitor Evolocumab, improves functional status (pain free walking time in particular, but also maximal walking time), lower extremity arterial perfusion and endothelial function (brachial endothelial reactivity).
Detailed description
This is a double-blinded, prospective, randomized, study in eighty-six subjects with clinical ASCVD with PAD on background treatment with maximal tolerated dose of a statin. Subjects will be assessed based on their medical history and physical examination. Eligible subjects must meet all inclusion criteria and none of the exclusion criteria (listed below). There will be a treatment group and a placebo group, each with equal number of participants (n=43 patients in each group). After consent and enrollment, subjects will have a venous blood sample drawn to perform serum circulating biomarkers of oxidative stress as oxidized low density lipoprotein (oxLDL), oxidized glutathione : reduced glutathione (GSH:GSSG) and soluble CD36 (sCD36). We will then perform: functional walking measurements, pain free walking time (PFWT), and (maximal walking time (MWT), lower extremity arterial perfusion assessment (rest ABI/TBI, post-exercise ABI and bilateral TcPO2), and brachial endothelial function testing (after hyperemia). Subjects will receive monthly subcutaneous injections of Evolocumab 420 mg or placebo injection. The study participants will be seen at three months and six months for follow up and a final assessment at 26 +/-2 weeks, all tests will be repeated for comparison from baseline and/or placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- This is a double-blinded, prospective, randomized, placebo-controlled study.
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: Evolocumab 140 mg/mL Subcutaneous Injection 1 milliliter (mL) pre-filled injector Pen x 3 for a monthly dose of 420 mg for 6 months.43 Patients with lower extremities Peripheral Arterial Disease on maximum statin therapy will receive in addition a monthly dose of evolocumab 420 mg via subcutaneous injections for 6 months. |
| Control Arm | Placebo comparator | Other: Placebo 1milliliter (mL) Subcutaneous Injection pre-filled injector Pen x 3 monthly for 6 months.43 Patients with lower extremities Peripheral Arterial Disease on maximum statin therapy will receive in addition a monthly dose of placebo via subcutaneous injections for 6 months. |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Signed informed consent.
- Age ≥40 to ≤85 years of age at the time of consent.
- Diagnosis of ASCVD with peripheral arterial disease, Rutherford class I-VI at the time of diagnosis, confirmed by ABI≤0.9 at rest or ABI≤0.8 after exercise, angiography, duplex ultrasound or history of lower extremity surgical or endovascular revascularization.
- At least 1 months from last intervention, including surgery or endovascular procedures.
- Stable on maximal tolerated doses of a lipid-lowering regimen for at least 4 weeks.
Key exclusion criteria (16 listed)
- Subjects with active, non-healed wounds.
- Subjects with anticipated need of cardiac or surgical revascularization procedures.
- Subjects with chronic inflammatory conditions or requiring chronic systemic corticosteroids.
- New York Heart Association (NYHA) class III or IV heart failure, or known left ventricular ejection fraction <30%.
- Uncontrolled arrhythmia.
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 |
|---|---|---|
| Evolocumab 140 mg/mL Subcutaneous Injection 1 milliliter (mL) pre-filled injector Pen x 3 for a monthly dose of 420 mg for 6 months.Also: RepathaThe study subjects randomized to the treatment study arm will receive monthly subcutaneous injections of evolocumab 420 mg in the abdomen, thigh or upper arm. The study drug (evolocumab) prefilled injector pens are provided by Amgen | Drug | Treatment Arm |
| Placebo 1milliliter (mL) Subcutaneous Injection pre-filled injector Pen x 3 monthly for 6 months.Also: ControlThe study subjects randomized to the treatment study arm will receive monthly subcutaneous injections of Placebo in the abdomen, thigh or upper arm. The Placebo prefilled injector pens are provided by Amgen | Other | Control Arm |
Primary outcome
Evolocumab effect in pain free walking time (PFWT) in patients with PAD
Time frame: six months
To evaluate change in pain free walking time (PFWT) in patients with PAD at baseline and after six months of therapy with Evolocumab. PFWT will be measured in minutes, using a graded treadmill Gardner protocol with a constant speed of 2 miles per hour, increasing by 2% grade every 2 minutes.
1 secondary outcome
Evolocumab effect in maximal walking time (MWT) in patients with PAD
Time frame: six months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2020.
- Individual participant dataSharing planned: No
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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.
Leonardo Clavijo, MD, PhD principal investigator
University of Southern California
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Evolocumab 140 mg/mL Subcutaneous Injection 1 milliliter (mL) pre-filled injector Pen x 3 for a monthly dose of 420 mg for 6 months. in people with Peripheral Arterial Disease, run by Leonardo Clavijo 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 16 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: status not confirmed, as of the sponsor's last update on 12 Mar 2020. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jorge Caro, MPH (323-382-7646, Jorge.Caro@med.usc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evolocumab effect in pain free walking time (PFWT) in patients with PAD (time frame: six months). 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 12 Mar 2020.