Effect of Lipoprotein(a) Elimination by Lipoprotein Apheresis on Cardiovascular Outcomes

NCT02791802 | Unknown DMC

• 1 other identifier: TUD-LPA16-001
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 12

Brief Summary

This multicenter multinational prospective two-arm matched-pair observational study aims to establish a prospective comparison of active lipoprotein apheresis treatment approved and conducted according to German guidelines for the indication of elevated Lp(a) versus a maximum tolerated lipid-lowering therapy as standard care. Due to the prospective character and the inclusion of a control arm, this will be the first clinical study that can confirm the relevance of the established approach to use lipoprotein apheresis in those subjects and its effects to reduce the individual cardiovascular risk. The optimized management of subjects in the control group (not receiving lipoprotein apheresis) will also help to clarify the controversial issue, to which extent intensive medical care per se can influence the occurence of subsequent cardiovascular events. Primary objective of the trial is to evaluate the clinical benefit of Lp(a) reduction using lipoprotein apheresis on myocardial infarction, PCI, CABG, fatal and non- fatal stroke, transient ischemic attack, interventional or surgical revascularization of peripheral arteries and death from cardiovascular disease. The primary objective of this study evaluates the clinical benefit of weekly lipoprotein apheresis in subjects with progressive cardiovascular disease, as accepted by the German Federal Joint Committee as indication for subjects with elevated Lp(a). Comparator will be matched subjects under maximum tolerated lipid lowering therapy without access to lipoprotein apheresis treatment. The clinical benefit will be defined as the reduction of the composite endpoint of major adverse cardiovascular events (MACE), defined as either myocardial infarction, PCI, CABG, fatal and non-fatal stroke, transient ischemic attack or death from cardiovascular disease over a period of at least 2 years after completion of visit 1b and until at least 60 events of the primary end-point occurred in group B. If the number of at least 60 documented primary endpoint events within 2 years of the completion of enrolment did not occur, the study will continue until this number of primary endpoint events has accumulated.

Conditions

Lipoprotein Types--Lp System Lp(A) Hyperlipoproteinemia

Keywords

Lipoprotein(a); lipoprotein/lipid apheresis; CV disease

Outcome Measures

Primary Outcomes (1)

• The primary end-point is an at least 10 % reduction of the proportion of events

  The primary end-point is an at least 10 % reduction of the proportion of events regarding the composite end-point consisting either of myocardial infarction, PCI, CABG, fatal and non-fatal stroke, transient ischemic attack, interventional or surgical revascularization of peripheral arteries or death from cardiovascular disease (or any combination of these) at the final visit.

  2 years of follow-up

Secondary Outcomes (3)

• An at least 10 % reduction of the proportion of events

  2 years of follow-up

• An at least 10 % reduction of the proportion of events

  2 years of follow-up

• An at least 10 % reduction of the proportion of events regarding the composite Secondary endpoints of the Trial

  2 years of follow-up

Other Outcomes (1)

• Reduction of individual endpoints

  2 years of follow-up

Study Arms (2)

Group A: Lipoprotein apheresis subjects

Established cardiovascular disease with disease progression indicated by one major cardiovascular event. With or without subsequent cardiovascular events/interventions, despite adequately controlled cardiovascular risk factors occuring within the last 2 years prior to enrolment. Corrected Low-density lipoprotein cholesterol \< 100 mg/dL (2.6 mmol/l) during 3 months prior to study enrolment. Additional lipoprotein apheresis is established following enrolment using the following established systems: Dextran-sulfate adsorption (DSA) from plasma and whole blood, Heparin-induced LDL precipitation apheresis (HELP®), Polyacrylate adsorption from whole blood and simple DFPP (DALI® and Monet®), ApoB100-immunoadsorption (TheraSorbLDL®, Temperature-optimized double filtration plasmapheresis (DFPP).

Group B: Control group

Established cardiovascular disease with disease progression indicated by one major cardiovascular event. With or without subsequent cardiovascular events/interventions, despite adequately controlled cardiovascular risk factors occuring within the last 2 years prior to enrolment. Corrected Low-density lipoprotein cholesterol \< 100 mg/dL (2.6 mmol/l) during 3 months prior to study enrolment. The control group will not undergo a sham apheresis procedure. It is an open trial.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

All participants have to be 18 years or older and need to be intellectually capable to understand and follow the study protocol. All subjects have to present with progressive cardiovascular disease and need to fulfill the criteria fixed in the recommendations by the German Joint Federal Committee (in German: "Gemeinsamer Bundesausschuss"; see section 1.2). In addition, a TEC has to verify presence of the treatment indication and will be blinded with respect to subject's group assignment. Apheresis subjects (group A) will be included in chronological order, since this will most likely reflect the natural distribution of disease in the general population. Control subjects (group B) will then be matched to the lipoprotein apheresis subjects entering the study.

You may qualify if:

• Age 18 - 70
• Male or female
• Written informed consent
• Lipoprotein(a) \> 60 mg/dL, or \> 120 nmol/L using an alternative laboratory method
• Corrected Low-density lipoprotein cholesterol \< 100 mg/dL (2.6 mmol/l) during 3 months prior to study enrolment.
• Established cardiovascular disease with disease progression indicated by one major cardiovascular event, which might be either
• myocardial infarction
• PCI
• CABG
• Stroke
• or revascularization of peripheral arteries using PTA, stenting or bypass surgery
• (with or without subsequent cardiovascular events/interventions) despite adequately controlled cardiovascular risk factors\* occuring within the last 2 years prior to enrolment
• (\*Hypertension, Diabetes, tobacco consumption, LDL Cholesterol)
• Platelet aggregation inhibitors or systemic anticoagulation according to cardiologic indication
• Positive recommendation by central Trial Expert Committee

You may not qualify if:

• Previous lipoprotein apheresis therapy
• Triglyceride concentrations ≥ 250 mg/dL (2.8 mmol/L)
• Known homozygous or compound heterozygous familial hypercholesterolemia
• Known type III hyperlipoproteinemia
• Pregnancy, breast feeding
• Active smoking, defined as any inhaled tobacco consumption with in the last 3 months
• Uncontrolled hypertension (\>160/90 mmHg)
• Active malignant disease
• Planned major surgical procedures
• Current participation in an interventional trial
• Contraindication for apheresis therapy (e. g. necessity of ACE inhibitor therapy)
• CKD stages IV and V
• Diabetes mellitus

Sponsors & Collaborators

• Technische Universität Dresden: lead
• Kaneka Pharma Europe N.V.: collaborator

Study Sites (12)

University Hospital Carl Gustav Carus

Dresden, Saxony, 01307, Germany

RECRUITING

Herz- und Diabeteszentrum NRW Universitätsklinik der Ruhr-Universität Bochum Klinik für Kardiologie

Bad Oeynhausen, 32545, Germany

RECRUITING

Dialyse am Kortumpark

Bochum, 44789, Germany

RECRUITING

Nephrologisches Zentrum Göttingen

Göttingen, 37075, Germany

RECRUITING

PHV Dialysezentrum

Meißen, 01662, Germany

RECRUITING

Klinikum der Universität München Campus Innenstadt

München, 80337, Germany

RECRUITING

Klinikum der Universität München Campus Großhadern

München, 81337, Germany

RECRUITING

Dialysezentrum Potsdam

Potsdam, 14471, Germany

RECRUITING

Nierenzentrum Reinbek

Reinbek, 21465, Germany

RECRUITING

Nephrocare Rostock GmbH Medizinisches Versorgungszentrum Südstadt

Rostock, 18059, Germany

RECRUITING

Nephrologisches Zentrum

Villingen-Schwenningen, 78052, Germany

RECRUITING

Heinrich Braun Klinikum

Zwickau, 08060, Germany

RECRUITING

Related Links

• Study Homepage

Biospecimen

Retention: SAMPLES WITH DNA

For biosampling one additional serum (9 ml), one EDTA vaccutainer (2.7 ml) and two PAXgene™ Blood RNA Tubes and 10 ml Urine samples will be provided for each subject.

MeSH Terms

Conditions

Lipoprotein Types--Lp System Lp(A) Hyperlipoproteinemia

Study Officials

• Bernd Hohenstein, MD

  Technische Universität Dresden

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne Kaul

CONTACT

+49 351 458; info@multiselect-trial.eu

Bernd Hohenstein, MD

CONTACT

+49 351 458; info@multiselect-trial.eu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med. Bernd Hohenstein

Study Record Dates

• First Submitted: May 26, 2016
• First Posted: June 7, 2016
• Study Start: August 1, 2016
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: May 2, 2022

Record last verified: 2022-04

Locations

DE (12)