Effect of Evolocumab in Patients With Critical Limb Ischemia (Evol-CLI)

NCT04306471 | Unknown Phase 4 DMC FDA Drug

• 2 other identifiers: 20187090HS-18-01010
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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

Keywords

CLI, Gangrene, Ischemia, Amputation

Outcome Measures

Primary Outcomes (1)

• Evolocumab effect on LDL cholesterol changes in patients with Critical Limb Ischemia

  To evaluate LDL cholesterol values in mg/dL in patients with Critical Limb Ischemia at baseline and after receiving three month therapy of Evolocumab compared to placebo. The LDL cholesterol value changes will be measured as least-squares mean percentage

  3 months

Secondary Outcomes (7)

• Evolocumab effect on Lower extremity arterial perfusion changes on ankle-brachial indices (ABI).

  12 months

• Evolocumab effect on Lower extremity arterial perfusion pressure changes on toe-brachial indices (TBI).

  12 months

• Evolocumab effect on Lower extremity microvascular perfusion changes.

  12 months

• Evolocumab effect on foot perfusion changes.

  6 months

• Evolocumab effect on Femoral arterial distensibility changes.

  12 months

Other Outcomes (3)

• Evolocumab effect on wound healing changes.

  6 months

• Evolocumab effect on serum levels of vascular endothelial growth factors changes.

  12 months

• Evolocumab effect on circulating endothelial progenitor cells changes

  12 months

Study Arms (2)

Treatment arm

EXPERIMENTAL

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

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

Control arm

PLACEBO COMPARATOR

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

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

Interventions

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

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.

Also known as: Repatha

Treatment arm

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

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.

Also known as: Control

Control arm

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Leonardo Clavijo: lead
• Amgen: collaborator

Study Sites (1)

University of Southern California

Los Angeles, California, 90033, United States

RECRUITING

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia; Gangrene; Ischemia

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Leonardo Clavijo, MD, PhD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jorge Caro, MPH

CONTACT

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

Melissa Ramos, RN

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Study subjects will be randomized, to receive either evolocumab or placebo. Each participant will have equal chance of receiving evolocumab or placebo. The study participant, the care provider and the investigator will not know to which study arm the participant was assigned.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associated Professor Cardiology, USC. Director Vascular Medicine and Peripheral Interventions Program Director, Interventional Cardiology Fellowship

Model Details: This is a double-blinded, prospective, randomized, pilot, study

Study Record Dates

• First Submitted: February 21, 2020
• First Posted: March 13, 2020
• Study Start: February 24, 2020
• Primary Completion: February 4, 2021
• Study Completion: February 4, 2022
• Last Updated: March 13, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)