Evolocumab Versus LDL Apheresis in Patients With Hypercholesterolemia

Comparative Pilot Study of the Effectiveness of Evolocumab Versus LDL Apheresis in Patients With Hypercholesterolemia

An open-label, prospective phase III study to compare the efficacy and safety of administering evolocumab versus treatment with LDLapheresis in patients with familial hypercholesterolemia and high cardiovascular risk.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Procedure: LDL apheresis; Drug: evolocumab; Drug: evolocumab and LDL apheresis

Detailed Description

STUDY DESIGN An open-label, prospective phase III study to compare the efficacy and safety of administering evolocumab versus treatment with LDLapheresis in patients with familial hypercholesterolemia and high cardiovascular risk.

STUDY POPULATION The chosen population is constituted by patients belonging to the LDL-apheresis program of the General University Hospital Gregorio Marañón with the diagnosis of familial hypercholesterolemia and a history of cardiovascular disease.

Number of patients expected to participate in the study according to the base of patients treated with LDL-apheresis: 10.

STUDY DESIGN:

Non-controlled intervention study to evaluate the different therapies in the treatment of hypercholesterolemia, in which each patient will be self-controlled. The variables will be analyzed during different phases

1. LDL-apheresis phase: Retrospectively during the previous year, pre- and postapheresis variables will be collected from the following lipid parameters: total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, atherogenicity index, Lipoprotein A, apo-A, apo- B; inflammatory parameters: PCR, ferritin, fibrinogen, leukocytes and polymorphonuclear and immunological parameters: immunoglobulins and complement.
2. Evolocumab phase: LDL-apheresis will be suspended for three months and Evolocumab administered: 140 mg / 15 days subcutaneously. The same parameters indicated in the previous section will be measured every two weeks.
3. Combined phase: During the following three months evolocumab will continue to be administered biweekly and the LDL-apheresis procedure will be spaced from biweekly to monthly, the same analytical parameters being measured again every two weeks.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients with age> 18 years
• hypercholesterolemia with LDL-cholesterol> 100 mg / dl in treatment with the maximum dose tolerated by statins and a history of severe cardiovascular disease
• patients who are included in the LDL-apheresis / biweekly program

Exclusion Criteria:

• contraindications to receive evolocumab according to technical data.
• hospital admission of any cause in the last three months prior to the inclusion of the study
• cardiovascular event in the three months prior to the inclusion of the study
• Inability to sign informed consent
• pregnant women and non-menopausal women who do not use at least one adequate contraceptive method

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: LDL apheresis; LDL apheresis during at least one year	Procedure: LDL apheresis; LDL apheresis biweekly
ACTIVE_COMPARATOR: Evolocumab; 140 mg evolocumab biweekly	Drug: evolocumab; evolocumab 140 mg/biweekly
ACTIVE_COMPARATOR: LDL apheresis and evolocumab; LDL-apheresis monthly evolocumab 140 mg biweekly	Drug: evolocumab and LDL apheresis; evolocumab 140 mg/biweekly LDL-apheresis monthly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
decrease in LDL-cholesterol (mg/dl)	decrease in LDL-cholesterol levels in all three phases: LDL-apheresis, evolocumab and combined	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease apo-B (mg/dl) levels	decrease in Apolipoprotein B levels in all three phases	9 months
Decrease lipoprotein A (mg/dl) levels	decrease in lipoprotein A levels in all three phases	9 months
Decrease in triglycerides (mg/dl) levels	Decrease in triglycerides levels in all three phases	9 months
any adverse effects	any serious adverse effects	9 months
Modification of C reactive protein	Effect of evolocumab and LDL-apheresis on C reactive protein levels (mg/l)	9 months
Modification of immunoglobulin G levels (mg/dl)	Effect of of evolocumab and LDL-apheresis on immunoglobulin (mg/dl)	9 months
Modification of immunoglobulin A levels (mg/dl)	Effect of evolocumab and LDLapheresis on immunoglobulin A (mg/dl)	9 months
Modification of complement levels (mg/dl)	Effect of evolocumab and LDL apheresis on serum complement (mg/dl)	9 months
Modification of serum fibrinogen (mg/dl)	Effect of evolocumab and LDL-apheresis on serum fibrinogen (mg/dl)	9 months

Collaborators and Investigators

• Sponsor: Hospital General Universitario Gregorio Marañon
• Investigators: Principal Investigator: Marian Goicoechea, MD, PhD, Hospital General Universitario Gregorio Marañón

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2017
• Primary Completion (ACTUAL): January 28, 2018
• Study Completion (ACTUAL): January 28, 2018

Study Registration Dates

• First Submitted: January 28, 2018
• First Submitted That Met QC Criteria: February 9, 2018
• First Posted (ACTUAL): February 12, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2018
• Last Update Submitted That Met QC Criteria: February 9, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: cardiovascular risk; evolocumab; LDL-apheresis
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Immunologic Factors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Antibodies, Monoclonal; Evolocumab
• Other Study ID Numbers: EVOLAFER01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No