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

Atherosclerosis Clinical Trial

— LaRCA  

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02133807
• Other study ID #: 01200953720
• Status: Completed
• Phase: Phase 3
• First received: May 6, 2014
• Last updated: May 9, 2014
• Start date: September 2009
• Est. completion date: June 2012

Study information

• Verified date: May 2014
• Source: Russian Cardiology Research and Production Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: June 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis
• Carotid Artery Diseases
• Coronary Artery Disease
• Coronary Disease

Intervention

Procedure:
• Specific Lp(a) apheresis
Specific Lp(a) apheresis procedures were carried out weekly with "Lp(a) Lipopak" columns (POCARD Ltd., Moscow, Russia) according to the standard protocol

Locations

Country	Name	City	State
Russian Federation	Russian Cardiology Research and Production Center	Moscow

Sponsors (3)

Lead Sponsor	Collaborator
Russian Cardiology Research and Production Center	Clinical Diagnostic Center MEDSI, Moscow State Government

Country where clinical trial is conducted

Russian Federation, 

References & Publications (1)

Safarova MS, Ezhov MV, Afanasieva OI, Matchin YG, Atanesyan RV, Adamova IY, Utkina EA, Konovalov GA, Pokrovsky SN. Effect of specific lipoprotein(a) apheresis on coronary atherosclerosis regression assessed by quantitative coronary angiography. Atheroscle — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Total Cholesterol (TC) Serum Level	Mean changes in TC level over the 18-month study period	From Baseline to Week 4, 36, 72	No
Other	Lipoprotein(a) (Lp(a)) serum levels	Mean changes in Lp(a) level over the 18-month study period	From Baseline to Week 4, 36, 72	No
Other	Low-density lipoprotein cholesterol (LDL-C) serum Level	Mean changes in LDL-C level over the 18-month study period	From Baseline to Week 4, 36, 72	No
Other	Change in corrected LDL-C (LDL-C corr) Serum level	Since all included patients had high Lp(a) levels, to avoid overestimation of LDL-C fraction estimated LDL-C levels were corrected for cholesterol derived from Lp(a).; Corrected LDL-C (LDL-C corr) was calculated using Dahlen's modification of the Friedewald formula: LDL-C corr = TC - (HDL-C) - (TG / 2.2) - (0.3 x Lp(a) / 38.7).; For values in mmol/L, Lp(a) in mg/dL	From Baseline to Week 4, 36, 72	No
Other	Change in triglycerides (TG) serum Level	Mean changes in TG level over the 18-month study period	From Baseline to Week 4, 36, 72	No
Other	Change in high-density lipoprotein cholesterol (HDL-C) serum level	Mean changes in HDL-C level over the 18-month study period	From Baseline to Week 4, 36, 72	No
Other	Change in hemoglobin level		From Baseline to Week 4, 36, 72	Yes
Other	Change in creatinine level		From Baseline to Week 4, 36, 72	Yes
Other	Change in creatine kinase (CK) level		From Baseline to Week 4, 36, 72	Yes
Other	Change in alanine transaminase (ALT) level		From Baseline to Week 4, 36, 72	Yes
Other	Change in aspartate transaminase (AST) level		From Baseline to Week 4, 36, 72	Yes
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No