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

May 9, 2014 updated by: Professor Sergei Pokrovsky, PhD, DSc, Russian Cardiology Research and Production Center

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Russian Federation
      • Moscow, Russian Federation, 121552
        • Russian Cardiology Research and Production Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Specific Lp(a) apheresis & Atorvastatin
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
Specific Lp(a) apheresis procedures were carried out weekly with "Lp(a) Lipopak" columns (POCARD Ltd., Moscow, Russia) according to the standard protocol
Other Names:
  • "Lp(a) Lipopak" immunoadsorption columns
No Intervention: Atorvastatin
Standard medical therapy in accordance with the recommendations for secondary prevention of CHD

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Percent Diameter Stenosis
Time Frame: 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.
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)
Time Frame: 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.
From Baseline to Week 36 (9 months) and to Week 72 (18 months)
Numbers of Coronary segments Showing Regression
Time Frame: 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
From baseline to End of study (Week 72)
Number of Carotid Segments showing Regression
Time Frame: 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.
From Baseline to End of study (Week 72)
Change in total atheroma volume (TAV) from baseline to 18 months post-therapy
Time Frame: From Baseline to Week 72
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
Time Frame: 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
From Baseline to Week 72
Change in relative amount of plaque components
Time Frame: 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
From baseline to Week 72
Numbers of Coronary Plaques Showing Regression
Time Frame: 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
From baseline to End of study (Week 72)
Acute change in Lp(a) level
Time Frame: 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
Once a week over 72 week period of active treatment
Change in quality of life (QOL)
Time Frame: 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
from baseline to week 72

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Cholesterol (TC) Serum Level
Time Frame: From Baseline to Week 4, 36, 72
Mean changes in TC level over the 18-month study period
From Baseline to Week 4, 36, 72
Lipoprotein(a) (Lp(a)) serum levels
Time Frame: From Baseline to Week 4, 36, 72
Mean changes in Lp(a) level over the 18-month study period
From Baseline to Week 4, 36, 72
Low-density lipoprotein cholesterol (LDL-C) serum Level
Time Frame: From Baseline to Week 4, 36, 72
Mean changes in LDL-C level over the 18-month study period
From Baseline to Week 4, 36, 72
Change in corrected LDL-C (LDL-C corr) Serum level
Time Frame: From Baseline to Week 4, 36, 72

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
Change in triglycerides (TG) serum Level
Time Frame: From Baseline to Week 4, 36, 72
Mean changes in TG level over the 18-month study period
From Baseline to Week 4, 36, 72
Change in high-density lipoprotein cholesterol (HDL-C) serum level
Time Frame: From Baseline to Week 4, 36, 72
Mean changes in HDL-C level over the 18-month study period
From Baseline to Week 4, 36, 72
Change in hemoglobin level
Time Frame: From Baseline to Week 4, 36, 72
From Baseline to Week 4, 36, 72
Change in creatinine level
Time Frame: From Baseline to Week 4, 36, 72
From Baseline to Week 4, 36, 72
Change in creatine kinase (CK) level
Time Frame: From Baseline to Week 4, 36, 72
From Baseline to Week 4, 36, 72
Change in alanine transaminase (ALT) level
Time Frame: From Baseline to Week 4, 36, 72
From Baseline to Week 4, 36, 72
Change in aspartate transaminase (AST) level
Time Frame: From Baseline to Week 4, 36, 72
From Baseline to Week 4, 36, 72

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Russian Cardiology Research and Production Center

Collaborators

Clinical Diagnostic Center MEDSI
Moscow State Government

Investigators

  • Principal Investigator: Sergei Pokrovsky, PhD, DSc, Russian Cardiology Research and Production Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Actual)

March 1, 2012

Study Completion (Actual)

June 1, 2012

Study Registration Dates

First Submitted

May 6, 2014

First Submitted That Met QC Criteria

May 6, 2014

First Posted (Estimate)

May 8, 2014

Study Record Updates

Last Update Posted (Estimate)

May 12, 2014

Last Update Submitted That Met QC Criteria

May 9, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01200953720

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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