Specific Lp(a) Apheresis for Regression of Coronary and Carotid Atherosclerosis

Study Overview
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Brief Summary
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To evaluate whether specific lipoprotein(a) apheresis on the top of optimal medical therapy could affect atherosclerotic disease burden in coronary and carotid arteries of coronary heart disease patients with elevated Lp(a) levels.

Detailed Description
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Following the hypothesis that if Lp(a) excess has a pathogenic role in atherogenesis, then specific elimination of circulating Lp(a) should affect plaque growth and stability, we evaluated the efficacy of Lp(a) apheresis on changes in coronary plaque volume and composition and carotid intima-media thickness in patients with CHD on the background of optimal medical treatment.

Official Title
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A 72-week, Prospective, Parallel-group, Partially Blinded, Controlled Phase IIIb Study Evaluating the Impact of Specific Lp(a) Apheresis on Atherosclerotic Disease Burden in Coronary Heart Disease Patients With High Lipoprotein(a) Level.

Conditions
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Atherosclerosis, Coronary Disease, Carotid Artery Diseases

Intervention / Treatment
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* Procedure: Specific Lp(a) apheresis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable coronary heart disease (CHD) requiring a clinically indicated coronary angiography. Lp(a) ≥50 mg/dL LDL-C <2.6 mmol/L (100 mg/dL) Signed written informed consent form to participate in the study Exclusion Criteria: history of acute coronary syndrome or surgical intervention within prior 3 months to inclusion chronic infectious and inflammatory diseases familial hypercholesterolemia TG ≥4.5 mmol/L (400 mg/dL) Active liver disease (ALT or AST >3 upper limit of normal (ULN), or total bilirubin >1.5 ULN); CK ≥3 ULN; Thyroid dysfunction; Renal dysfunction (creatinine clearance (Cockcroft-Gault Equation) ≤30 ml/min); Uncontrolled diabetes (HbA1c ≥7.0%); Coagulopathies; Lipid-lowering drugs, except statins for the last month Known statin or immunoadsorption intolerance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Specific Lp(a) apheresis & Atorvastatin<br>Specific Lp(a) apheresis was performed with Lp(a) Lipopak immunosorbent columns (POCARD Ltd., Moscow, Russia) with sheep polyclonal monospecific antibodies against human Lp(a)/apo(a) weekly during 18 months. On the background - standard medical therapy in accordance with the recommendations for secondary prevention of CHD. | Procedure: Specific Lp(a) apheresis<br>* Specific Lp(a) apheresis procedures were carried out weekly with Lp(a) Lipopak columns (POCARD Ltd., Moscow, Russia) according to the standard protocol<br>* Other names: Lp(a) Lipopak immunoadsorption columns;|
| No Intervention: Atorvastatin<br>Standard medical therapy in accordance with the recommendations for secondary prevention of CHD | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Percent Diameter Stenosis | The absolute change from baseline to 18 months in mean percent diameter stenosis, determined by quantitative coronary angiography (QCA) as the narrowest lesion in each segment and calculated as: ((reference diameter-minimal lumen diameter (MLD))/reference diameter)x100. | From Baseline to End of Study (Week 72) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean carotid intima-media thickness (IMT) | Change from baseline in mean carotid IMT, as measured by duplex ultrasonography of common carotid arteries after 9 and 18 months. | From Baseline to Week 36 (9 months) and to Week 72 (18 months) | 
| Numbers of Coronary segments Showing Regression | Clinically relevant regression or progression was defined as a change from baseline to follow up of ≥10% for percent diameter stenosis | From baseline to End of study (Week 72) | 
| Number of Carotid Segments showing Regression | Carotid IMT progression criterion for the 18 months of treatment was considered as growth rate of 0.02 mm (0.015 mm/yr). No changes or reduction in carotid IMT ≥ 0,02 mm served as criterion of stabilization and regression of carotid atherosclerosis, respectively. | From Baseline to End of study (Week 72) | 
| Change in total atheroma volume (TAV) from baseline to 18 months post-therapy | TAV at baseline - TAV at Week 72 assessed by intravascular ultrasound (IVUS) imaging of a targeted coronary artery | From Baseline to Week 72 | 
| Change in absolute volumes of plaque components | Mean change in absolute volumes of plaque components: fibrotic, fibrofatty, necrotic core or dense calcium, assessed by radiofrequency intravascular ultrasonographic (IVUS) imaging at baseline and 18 months post-therapy | From Baseline to Week 72 | 
| Change in relative amount of plaque components | Mean change in relative amounts of plaque components: fibrotic, fibrofatty, necrotic core or dense calcium, assessed by radiofrequency intravascular ultrasonographic (IVUS) imaging at baseline and 18 months post-therapy | From baseline to Week 72 | 
| Numbers of Coronary Plaques Showing Regression | Regression was defined as decrease in TAV for all anatomically comparable cross sectional areas of targeted coronary artery from baseline of ≥ 0,1 mm cubed | From baseline to End of study (Week 72) | 
| Acute change in Lp(a) level | Difference in Lp(a) concentration before and after specific Lp(a) apheresis procedure calculated as the mean of all measurements | Once a week over 72 week period of active treatment | 
| Change in quality of life (QOL) | To evaluate the impact of the specific Lp(a) removal therapy on the quality of life using Seattle Angina Questionnaire (SAQ) and Exercise stress test as compared with standard guideline-driven medical therapy of CHD patients | from baseline to week 72 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lipoprotein(a);, Lp(a) immunoadsorption;, Apheresis;, Coronary atherosclerosis;, Carotid Atherosclerosis;, Intima-media thickness;, Regression;, Quantitative Coronary Angiography;, Intravascular Ultrasound;, Virtual Histology;, Plaque;, Atorvastatin;