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

NCT ID: NCT02791802

Last Updated: 2022-05-02

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 1000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2022-12-31

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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).

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

1. Age 18 - 70

2. Male or female

3. Written informed consent

4. Lipoprotein(a) > 60 mg/dL, or > 120 nmol/L using an alternative laboratory method

5. Corrected Low-density lipoprotein cholesterol < 100 mg/dL (2.6 mmol/l) during 3 months prior to study enrolment.

6. 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)

7. Platelet aggregation inhibitors or systemic anticoagulation according to cardiologic indication

8. Positive recommendation by central Trial Expert Committee

Exclusion Criteria

1. Previous lipoprotein apheresis therapy

2. Triglyceride concentrations ≥ 250 mg/dL (2.8 mmol/L)

3. Known homozygous or compound heterozygous familial hypercholesterolemia

4. Known type III hyperlipoproteinemia

5. Pregnancy, breast feeding

6. Active smoking, defined as any inhaled tobacco consumption with in the last 3 months

7. Uncontrolled hypertension (>160/90 mmHg)

8. Active malignant disease

9. Planned major surgical procedures

10. Current participation in an interventional trial

11. Contraindication for apheresis therapy (e. g. necessity of ACE inhibitor therapy)

12. CKD stages IV and V

13. Diabetes mellitus

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kaneka Pharma Europe N.V.

INDUSTRY

Sponsor Role: collaborator

Technische Universität Dresden

OTHER

Sponsor Role: lead

Responsible Party

Prof. Bernd Hohenstein

Prof. Dr. med. Bernd Hohenstein

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bernd Hohenstein, MD

Role: PRINCIPAL_INVESTIGATOR

Technische Universität Dresden

Locations

University Hospital Carl Gustav Carus

Dresden, Saxony, Germany

Site Status: RECRUITING

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

Bad Oeynhausen, , Germany

Site Status: RECRUITING

Dialyse am Kortumpark

Bochum, , Germany

Site Status: RECRUITING

Nephrologisches Zentrum Göttingen

Göttingen, , Germany

Site Status: RECRUITING

PHV Dialysezentrum

Meißen, , Germany

Site Status: RECRUITING

Klinikum der Universität München Campus Innenstadt

München, , Germany

Site Status: RECRUITING

Klinikum der Universität München Campus Großhadern

München, , Germany

Site Status: RECRUITING

Dialysezentrum Potsdam

Potsdam, , Germany

Site Status: RECRUITING

Nierenzentrum Reinbek

Reinbek, , Germany

Site Status: RECRUITING

Nephrocare Rostock GmbH Medizinisches Versorgungszentrum Südstadt

Rostock, , Germany

Site Status: RECRUITING

Nephrologisches Zentrum

Villingen-Schwenningen, , Germany

Site Status: RECRUITING

Heinrich Braun Klinikum

Zwickau, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Anne Kaul

Role: CONTACT

info@multiselect-trial.eu

+49 351 458 ext. 3075

Bernd Hohenstein, MD

Role: CONTACT

info@multiselect-trial.eu

+49 351 458 ext. 3075

Facility Contacts

Ulrich Julius, MD

Role: primary

ulrich.julius@ukdd.de

+493514582176

Klaus Peter Mellwig, MD

Role: primary

Velthof Ansgar, MD

Role: primary

Volker Schettler, MD

Role: primary

Beate Schulze, MD

Role: primary

Anja Vogt, MD

Role: primary

Klaus Parhofer, MD

Role: primary

Jens Ringel, MD

Role: primary

Markus Reinbek, MD

Role: primary

Wolfgang Ramlow, MD

Role: primary

Bernd Hohenstein, MD

Role: primary

Role: backup

hohenstein@nephrologie-vs.de

Jens Gerth, MD

Role: primary

Related Links

http://www.multiselect-trial.eu

Study Homepage

Other Identifiers

TUD-LPA16-001

Identifier Type: -

Identifier Source: org_study_id