Clinical trial NCT02133807: Specific Lp(a) Apheresis for Regression of Coronary and Carotid Atherosclerosis
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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;
Lead sponsor: Russian Cardiology Research and Production Center
Sponsor class: OTHER
Collaborators: name: Clinical Diagnostic Center MEDSI
name: Moscow State Government
First posted: 2014-05-08
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Percent Diameter Stenosis
timeFrame: From Baseline to End of Study (Week 72)
Secondary outcomes:
measure: Change in mean carotid intima-media thickness (IMT)
timeFrame: From Baseline to Week 36 (9 months) and to Week 72 (18 months)
measure: Numbers of Coronary segments Showing Regression
timeFrame: From baseline to End of study (Week 72)
measure: Number of Carotid Segments showing Regression
timeFrame: From Baseline to End of study (Week 72)
measure: Change in total atheroma volume (TAV) from baseline to 18 months post-therapy
timeFrame: From Baseline to Week 72
measure: Change in absolute volumes of plaque components
timeFrame: From Baseline to Week 72
measure: Change in relative amount of plaque components
timeFrame: From baseline to Week 72
measure: Numbers of Coronary Plaques Showing Regression
timeFrame: From baseline to End of study (Week 72)
measure: Acute change in Lp(a) level
timeFrame: Once a week over 72 week period of active treatment
measure: Change in quality of life (QOL)
timeFrame: from baseline to week 72
Other outcomes:
measure: Total Cholesterol (TC) Serum Level
timeFrame: From Baseline to Week 4, 36, 72
measure: Lipoprotein(a) (Lp(a)) serum levels
timeFrame: From Baseline to Week 4, 36, 72
measure: Low-density lipoprotein cholesterol (LDL-C) serum Level
timeFrame: From Baseline to Week 4, 36, 72
measure: Change in corrected LDL-C (LDL-C corr) Serum level
timeFrame: From Baseline to Week 4, 36, 72
measure: Change in triglycerides (TG) serum Level
timeFrame: From Baseline to Week 4, 36, 72
measure: Change in high-density lipoprotein cholesterol (HDL-C) serum level
timeFrame: From Baseline to Week 4, 36, 72
measure: Change in hemoglobin level
timeFrame: From Baseline to Week 4, 36, 72
measure: Change in creatinine level
timeFrame: From Baseline to Week 4, 36, 72
measure: Change in creatine kinase (CK) level
timeFrame: From Baseline to Week 4, 36, 72
measure: Change in alanine transaminase (ALT) level
timeFrame: From Baseline to Week 4, 36, 72
measure: Change in aspartate transaminase (AST) level
timeFrame: From Baseline to Week 4, 36, 72
Locations:
city: Moscow
country: Russian Federation
facility: Russian Cardiology Research and Production Center
Study officials:
affiliation: Russian Cardiology Research and Production Center
name: Sergei Pokrovsky, PhD, DSc
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: Pokrovsky SN, Afanasieva OI, Ezhov MV. Lipoprotein(a) apheresis. Curr Opin Lipidol. 2016 Aug;27(4):351-8. doi: 10.1097/MOL.0000000000000319.
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.