Back to resultsSpecific Lp(a) Apheresis for Regression of Coronary and Carotid Atherosclerosis (LaRCA)
Primary Purpose
Atherosclerosis, Coronary Disease, Carotid Artery Diseases
Status
Completed
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
Specific Lp(a) apheresis
Sponsored by
About this trial
This is an interventional treatment trial for Atherosclerosis focused on measuring Lipoprotein(a);, Lp(a) immunoadsorption;, Apheresis;, Coronary atherosclerosis;, Carotid Atherosclerosis;, Intima-media thickness;, Regression;, Quantitative Coronary Angiography;, Intravascular Ultrasound;, Virtual Histology;, Plaque;, Atorvastatin;
Eligibility Criteria
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
Sites / Locations
- Russian Cardiology Research and Production Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Specific Lp(a) apheresis & Atorvastatin
Atorvastatin
Arm Description
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.
Standard medical therapy in accordance with the recommendations for secondary prevention of CHD
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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
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.
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
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
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
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
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
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
Full Information
NCT ID
NCT02133807
First Posted
May 6, 2014
Last Updated
May 9, 2014
Sponsor
Russian Cardiology Research and Production Center
Collaborators
Clinical Diagnostic Center MEDSI, Moscow State Government
1. Study Identification
Unique Protocol Identification Number
NCT02133807
Brief Title
Specific Lp(a) Apheresis for Regression of Coronary and Carotid Atherosclerosis
Acronym
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.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
June 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Russian Cardiology Research and Production Center
Collaborators
Clinical Diagnostic Center MEDSI, Moscow State Government
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atherosclerosis, Coronary Disease, Carotid Artery Diseases
Keywords
Lipoprotein(a);, Lp(a) immunoadsorption;, Apheresis;, Coronary atherosclerosis;, Carotid Atherosclerosis;, Intima-media thickness;, Regression;, Quantitative Coronary Angiography;, Intravascular Ultrasound;, Virtual Histology;, Plaque;, Atorvastatin;
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Non-Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Specific Lp(a) apheresis & Atorvastatin
Arm Type
Experimental
Arm Description
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.
Arm Title
Atorvastatin
Arm Type
No Intervention
Arm Description
Standard medical therapy in accordance with the recommendations for secondary prevention of CHD
Intervention Type
Procedure
Intervention Name(s)
Specific Lp(a) apheresis
Other Intervention Name(s)
"Lp(a) Lipopak" immunoadsorption columns
Intervention Description
Specific Lp(a) apheresis procedures were carried out weekly with "Lp(a) Lipopak" columns (POCARD Ltd., Moscow, Russia) according to the standard protocol
Primary Outcome Measure Information:
Title
Change in Percent Diameter Stenosis
Description
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.
Time Frame
From Baseline to End of Study (Week 72)
Secondary Outcome Measure Information:
Title
Change in mean carotid intima-media thickness (IMT)
Description
Change from baseline in mean carotid IMT, as measured by duplex ultrasonography of common carotid arteries after 9 and 18 months.
Time Frame
From Baseline to Week 36 (9 months) and to Week 72 (18 months)
Title
Numbers of Coronary segments Showing Regression
Description
Clinically relevant regression or progression was defined as a change from baseline to follow up of ≥10% for percent diameter stenosis
Time Frame
From baseline to End of study (Week 72)
Title
Number of Carotid Segments showing Regression
Description
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.
Time Frame
From Baseline to End of study (Week 72)
Title
Change in total atheroma volume (TAV) from baseline to 18 months post-therapy
Description
TAV at baseline - TAV at Week 72 assessed by intravascular ultrasound (IVUS) imaging of a targeted coronary artery
Time Frame
From Baseline to Week 72
Title
Change in absolute volumes of plaque components
Description
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
Time Frame
From Baseline to Week 72
Title
Change in relative amount of plaque components
Description
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
Time Frame
From baseline to Week 72
Title
Numbers of Coronary Plaques Showing Regression
Description
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
Time Frame
From baseline to End of study (Week 72)
Title
Acute change in Lp(a) level
Description
Difference in Lp(a) concentration before and after specific Lp(a) apheresis procedure calculated as the mean of all measurements
Time Frame
Once a week over 72 week period of active treatment
Title
Change in quality of life (QOL)
Description
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
Time Frame
from baseline to week 72
Other Pre-specified Outcome Measures:
Title
Total Cholesterol (TC) Serum Level
Description
Mean changes in TC level over the 18-month study period
Time Frame
From Baseline to Week 4, 36, 72
Title
Lipoprotein(a) (Lp(a)) serum levels
Description
Mean changes in Lp(a) level over the 18-month study period
Time Frame
From Baseline to Week 4, 36, 72
Title
Low-density lipoprotein cholesterol (LDL-C) serum Level
Description
Mean changes in LDL-C level over the 18-month study period
Time Frame
From Baseline to Week 4, 36, 72
Title
Change in corrected LDL-C (LDL-C corr) Serum level
Description
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
Time Frame
From Baseline to Week 4, 36, 72
Title
Change in triglycerides (TG) serum Level
Description
Mean changes in TG level over the 18-month study period
Time Frame
From Baseline to Week 4, 36, 72
Title
Change in high-density lipoprotein cholesterol (HDL-C) serum level
Description
Mean changes in HDL-C level over the 18-month study period
Time Frame
From Baseline to Week 4, 36, 72
Title
Change in hemoglobin level
Time Frame
From Baseline to Week 4, 36, 72
Title
Change in creatinine level
Time Frame
From Baseline to Week 4, 36, 72
Title
Change in creatine kinase (CK) level
Time Frame
From Baseline to Week 4, 36, 72
Title
Change in alanine transaminase (ALT) level
Time Frame
From Baseline to Week 4, 36, 72
Title
Change in aspartate transaminase (AST) level
Time Frame
From Baseline to Week 4, 36, 72
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sergei Pokrovsky, PhD, DSc
Organizational Affiliation
Russian Cardiology Research and Production Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Russian Cardiology Research and Production Center
City
Moscow
ZIP/Postal Code
121552
Country
Russian Federation
12. IPD Sharing Statement
Citations:
PubMed Identifier
23357149
Citation
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. Atheroscler Suppl. 2013 Jan;14(1):93-9. doi: 10.1016/j.atherosclerosissup.2012.10.015.
Results Reference
result
PubMed Identifier
29096833
Citation
Pokrovsky SN, Afanasieva OI, Safarova MS, Balakhonova TV, Matchin YG, Adamova IYU, Konovalov GA, Ezhov MV. Specific Lp(a) apheresis: A tool to prove lipoprotein(a) atherogenicity. Atheroscler Suppl. 2017 Nov;30:166-173. doi: 10.1016/j.atherosclerosissup.2017.05.004. Epub 2017 May 31.
Results Reference
derived
PubMed Identifier
27213629
Citation
Pokrovsky SN, Afanasieva OI, Ezhov MV. Lipoprotein(a) apheresis. Curr Opin Lipidol. 2016 Aug;27(4):351-8. doi: 10.1097/MOL.0000000000000319.
Results Reference
derived
PubMed Identifier
25936321
Citation
Ezhov MV, Safarova MS, Afanasieva OI, Pogorelova OA, Tripoten MI, Adamova IY, Konovalov GA, Balakhonova TV, Pokrovsky SN. Specific Lipoprotein(a) apheresis attenuates progression of carotid intima-media thickness in coronary heart disease patients with high lipoprotein(a) levels. Atheroscler Suppl. 2015 May;18:163-9. doi: 10.1016/j.atherosclerosissup.2015.02.025.
Results Reference
derived
Learn more about this trial
Specific Lp(a) Apheresis for Regression of Coronary and Carotid Atherosclerosis
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