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

Phase 3

Completed

• Conditions: Atherosclerosis; Coronary Disease; Carotid Artery Diseases
• Interventions: Procedure: Specific Lp(a) apheresis

• Registration Number: NCT02133807
• Lead Sponsor: Russian Cardiology Research and Production Center

Brief Summary

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

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.

Study Timeline

• Study Start: 2009-09
• Primary Completion: 2012-03
• Study Completion: 2012-06
• Status Verified: 2014-05
• Study First Submitted: 2014-05-06
• Study First Submitted QC: 2014-05-06
• Study First Posted: 2014-05-08
• Last Update Submitted: 2014-05-09
• Last Update Posted: 2014-05-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Specific Lp(a) apheresis & Atorvastatin	Specific Lp(a) apheresis	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.

Primary Outcome Measures

Name	Time	Method
Change in Percent Diameter Stenosis	From Baseline to End of Study (Week 72)	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.

Secondary Outcome Measures

Name	Time	Method
Change in mean carotid intima-media thickness (IMT)	From Baseline to Week 36 (9 months) and to Week 72 (18 months)	Change from baseline in mean carotid IMT, as measured by duplex ultrasonography of common carotid arteries after 9 and 18 months.
Change in relative amount of plaque components	From baseline to Week 72	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
Numbers of Coronary segments Showing Regression	From baseline to End of study (Week 72)	Clinically relevant regression or progression was defined as a change from baseline to follow up of ≥10% for percent diameter stenosis
Acute change in Lp(a) level	Once a week over 72 week period of active treatment	Difference in Lp(a) concentration before and after specific Lp(a) apheresis procedure calculated as the mean of all measurements
Number of Carotid Segments showing Regression	From Baseline to End of study (Week 72)	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.
Change in total atheroma volume (TAV) from baseline to 18 months post-therapy	From Baseline to Week 72	TAV at baseline - TAV at Week 72 assessed by intravascular ultrasound (IVUS) imaging of a targeted coronary artery
Change in absolute volumes of plaque components	From Baseline to Week 72	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
Numbers of Coronary Plaques Showing Regression	From baseline to End of study (Week 72)	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
Change in quality of life (QOL)	from baseline to week 72	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

Trial Locations

Locations (1)

Russian Cardiology Research and Production Center; 🇷🇺 Moscow, Russian Federation