Recruiting

Evolocumab

Sponsor:

Leonardo Clavijo

Code:

NCT04306471

Conditions

Critical Limb Ischemia

Eligibility Criteria

Sex: All

Age: 40 - 70+

Healthy Volunteers: Not accepted

Interventions

Evolocumab 140mg/mL Injector 1milliliter (mL) Pen x 3 for a monthly dose of 420 mg for 12 months.

Placebo 1 milliliter (mL) Injector Pen x 3 monthly for 12 months

Study Details

Brief summary:

Critical limb ischemia (CLI), is the most severe form of peripheral arterial disease (PAD), and clinically is characterized by pain at rest or non-healing ulcers of the lower extremities. Also, is associated with increased risk of cardiovascular death, myocardial infarction (MI), stroke and amputation.

Feringa et al. demonstrated in a study of 1,374 patients with PAD that all cause and cardiac related mortality rates were lower in patients at higher statin dose and lower levels of low-density lipoprotein cholesterol (LDL).

Patients with CLI statin therapy and lower LDL levels improve amputation-free survival and patency after revascularization procedures.

In the FOURIER trial, LDL cholesterol reduction with the PCSK9 inhibitor evolocumab in patients with symptomatic PAD with or without prior myocardial infarction or stroke was associated with improved major adverse cardiac events (MACE) and major adverse limb events (MALE) at 2-years.

The effect of evolocumab in patients with CLI , after a recent arterial revascularization and active wounds is not known, also it is not known whether the cholesterol lowering effect of evolocumab in this group of patients is equivalent to that of non-CLI PAD patients and what the effect is on arterial perfusion, wound healing and other biological markers of vascular physiology.

This study aims to investigate the effect of evolocumab in patients with CLI on maximally tolerated lipid lowering therapy with a statin for one year after an index CLI event, requiring revascularization.

Conditions

Critical Limb Ischemia

Study ID

NCT04306471

Start date

Feb 24, 2020

Status verified date

Mar, 2020

Completion date

Feb 4, 2022

Anticipated

Primary completion date

Feb 4, 2021

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 40 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Signed informed consent.
  • Age ≥40 to ≤85 years of age at the time of consent.
  • Diagnosis CLI, Rutherford class IV to VI at the time of diagnosis, toe pressure ≤30 mmHg in non-diabetics or ≤40 mmHg in diabetics, angiography, duplex ultrasound or history of lower extremity surgical or endovascular revascularization for CLI.
  • Stable on maximal tolerated dose of a statin, defined as the highest dose of statin (preferably atorvastatin or rosuvastatin) tolerated by the patient without side effects for at least one month.

Exclusion Criteria:

  • Less than 1 month from last revascularization procedure including surgery or endovascular procedures.
  • Subjects with active infection.
  • Diabetes therapy with canagliflozin
  • Subjects who in the opinion of the Principal Investigator will likely require additional. amputation or revascularization procedures during the duration of the study.
  • 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.
  • Untreated thyroid disease.
  • Severe chronic renal disease with estimated glomerular filtration rate (eGFR) <20 mL/min.
  • Liver disease with aspartate 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.

Study Design

Enrollment

32 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment arm

16 Patients with Critical Limb Ischemia on maximum statin therapy will receive in addition the study intervention involving a monthly subcutaneous injection of evolocumab 420 mg for 12 months

placebo comparator: Control arm

16 Patients with Critical Limb Ischemia on maximum statin therapy will receive in addition a Placebo subcutaneous injection for 12 months.

Interventions

Evolocumab 140mg/mL Injector 1milliliter (mL) Pen x 3 for a monthly dose of 420 mg for 12 months.

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 to be provided by Amgen.

Placebo 1 milliliter (mL) Injector Pen x 3 monthly for 12 months

The study subjects randomized to the control study arm will receive monthly subcutaneous injections of placebo 1 mL x 3 in the abdomen, thigh or upper arm. The study placebo prefilled injector pens are to be provided by Amgen.

Primary outcome measure

  • Evolocumab effect on LDL cholesterol changes in patients with Critical Limb Ischemia [ Time Frame: 3 months ]

Central Contacts and Locations

Central contacts

Jorge Caro, MPH

323-382-7646Jorge.Caro@med.usc.edu

Melissa Ramos, RN

323-442-7983Melissa.Ramos@med.usc.edu

Locations

University of Southern California

Recruiting

Los Angeles, California, United States, 90033

Contacts

Jorge Caro, MPH

323-382-7646Jorge.Caro@med.usc.edu

Melissa Ramos, RN

323-442-7983Melissa.Ramos@med.usc.edu

More Information

Sponsor

Leonardo Clavijo

Last update posted

Mar 13, 2020

Last verified

Mar, 2020

Keywords

  • CLI, Gangrene, Ischemia, Amputation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Leonardo Clavijo on 2020-03-13.