Evolocumab Versus LDL Apheresis in Patients With Hypercholesterolemia

Study Overview
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Brief Summary
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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.

Detailed Description
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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 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. 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. 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.

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

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: evolocumab
* Drug: evolocumab and LDL apheresis
* Procedure: LDL apheresis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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 Phase LDL apheresis: evolocumab phase Combined phase
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: LDL apheresis<br>LDL apheresis during at least one year | Procedure: LDL apheresis<br>* LDL apheresis biweekly<br>|
| Active Comparator: Evolocumab<br>140 mg evolocumab biweekly | Drug: evolocumab<br>* evolocumab 140 mg/biweekly<br>|
| Active Comparator: LDL apheresis and evolocumab<br>LDL-apheresis monthly evolocumab 140 mg biweekly | Drug: evolocumab and LDL apheresis<br>* evolocumab 140 mg/biweekly LDL-apheresis monthly<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiovascular risk, evolocumab, LDL-apheresis