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

This study has been completed.
Sponsor:
Collaborators:
Clinical Diagnostic Center MEDSI
Moscow State Government
Information provided by (Responsible Party):
Professor Sergei Pokrovsky, PhD, DSc, Russian Cardiology Research and Production Center
ClinicalTrials.gov Identifier:
NCT02133807
First received: May 6, 2014
Last updated: May 9, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Atherosclerosis
Coronary Disease
Carotid Artery Diseases
Procedure: Specific Lp(a) apheresis
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Russian Cardiology Research and Production Center:

Primary Outcome Measures:
  • Change in Percent Diameter Stenosis [ Time Frame: From Baseline to End of Study (Week 72) ] [ Designated as safety issue: No ]
    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) [ Time Frame: From Baseline to Week 36 (9 months) and to Week 72 (18 months) ] [ Designated as safety issue: No ]
    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 [ Time Frame: From baseline to End of study (Week 72) ] [ Designated as safety issue: No ]
    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 [ Time Frame: From Baseline to End of study (Week 72) ] [ Designated as safety issue: No ]
    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 [ Time Frame: From Baseline to Week 72 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From Baseline to Week 72 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From baseline to Week 72 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From baseline to End of study (Week 72) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Once a week over 72 week period of active treatment ] [ Designated as safety issue: No ]
    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) [ Time Frame: from baseline to week 72 ] [ Designated as safety issue: No ]
    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


Other Outcome Measures:
  • Total Cholesterol (TC) Serum Level [ Time Frame: From Baseline to Week 4, 36, 72 ] [ Designated as safety issue: No ]
    Mean changes in TC level over the 18-month study period

  • Lipoprotein(a) (Lp(a)) serum levels [ Time Frame: From Baseline to Week 4, 36, 72 ] [ Designated as safety issue: No ]
    Mean changes in Lp(a) level over the 18-month study period

  • Low-density lipoprotein cholesterol (LDL-C) serum Level [ Time Frame: From Baseline to Week 4, 36, 72 ] [ Designated as safety issue: No ]
    Mean changes in LDL-C level over the 18-month study period

  • Change in corrected LDL-C (LDL-C corr) Serum level [ Time Frame: From Baseline to Week 4, 36, 72 ] [ Designated as safety issue: No ]

    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


  • Change in triglycerides (TG) serum Level [ Time Frame: From Baseline to Week 4, 36, 72 ] [ Designated as safety issue: No ]
    Mean changes in TG level over the 18-month study period

  • Change in high-density lipoprotein cholesterol (HDL-C) serum level [ Time Frame: From Baseline to Week 4, 36, 72 ] [ Designated as safety issue: No ]
    Mean changes in HDL-C level over the 18-month study period

  • Change in hemoglobin level [ Time Frame: From Baseline to Week 4, 36, 72 ] [ Designated as safety issue: Yes ]
  • Change in creatinine level [ Time Frame: From Baseline to Week 4, 36, 72 ] [ Designated as safety issue: Yes ]
  • Change in creatine kinase (CK) level [ Time Frame: From Baseline to Week 4, 36, 72 ] [ Designated as safety issue: Yes ]
  • Change in alanine transaminase (ALT) level [ Time Frame: From Baseline to Week 4, 36, 72 ] [ Designated as safety issue: Yes ]
  • Change in aspartate transaminase (AST) level [ Time Frame: From Baseline to Week 4, 36, 72 ] [ Designated as safety issue: Yes ]

Enrollment: 32
Study Start Date: September 2009
Study Completion Date: June 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: "Lp(a) Lipopak" immunoadsorption columns
No Intervention: Atorvastatin
Standard medical therapy in accordance with the recommendations for secondary prevention of CHD

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02133807

Locations
Russian Federation
Russian Cardiology Research and Production Center
Moscow, Russian Federation, 121552
Sponsors and Collaborators
Russian Cardiology Research and Production Center
Clinical Diagnostic Center MEDSI
Moscow State Government
Investigators
Principal Investigator: Sergei Pokrovsky, PhD, DSc Russian Cardiology Research and Production Center
  More Information

No publications provided

Responsible Party: Professor Sergei Pokrovsky, PhD, DSc, Chair of the Laboratory of Atherosclerosis, Russian Cardiology Research and Production Center
ClinicalTrials.gov Identifier: NCT02133807     History of Changes
Other Study ID Numbers: 01200953720
Study First Received: May 6, 2014
Last Updated: May 9, 2014
Health Authority: Russia: Ministry of Health of the Russian Federation

Keywords provided by Russian Cardiology Research and Production Center:
Lipoprotein(a);
Lp(a) immunoadsorption;
Apheresis;
Coronary atherosclerosis;
Carotid Atherosclerosis;
Intima-media thickness;
Regression;
Quantitative Coronary Angiography;
Intravascular Ultrasound;
Virtual Histology;
Plaque;
Atorvastatin;

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Coronary Disease
Coronary Artery Disease
Carotid Artery Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Myocardial Ischemia
Heart Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014