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

Lipoprotein Types--Lp System Lp(A) Hyperlipoproteinemia Clinical Trial

— MultiSELECt  

Official title:

A European Multicenter Study on the Effect of Lipoprotein(a) Elimination by Lipoprotein Apheresis on Cardiovascular Outcomes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02791802
• Other study ID #: TUD-LPA16-001
• Status: Recruiting
• Start date: August 2016
• Est. completion date: December 2022

Study information

• Verified date: April 2022
• Source: Technische Universität Dresden
• Contact: Anne Kaul
• Phone: +49 351 458
• Email: info[@]multiselect-trial.eu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperlipidemias
• Hyperlipoproteinemias
• Lipoprotein Types--Lp System Lp(A) Hyperlipoproteinemia

Locations

Country	Name	City	State
Germany	Herz- und Diabeteszentrum NRW Universitätsklinik der Ruhr-Universität Bochum Klinik für Kardiologie	Bad Oeynhausen
Germany	Dialyse am Kortumpark	Bochum
Germany	University Hospital Carl Gustav Carus	Dresden	Saxony
Germany	Nephrologisches Zentrum Göttingen	Göttingen
Germany	PHV Dialysezentrum	Meißen
Germany	Klinikum der Universität München Campus Großhadern	Muenchen
Germany	Klinikum der Universität München Campus Innenstadt	Muenchen
Germany	Dialysezentrum Potsdam	Potsdam
Germany	Nierenzentrum Reinbek	Reinbek
Germany	Nephrocare Rostock GmbH Medizinisches Versorgungszentrum Südstadt	Rostock
Germany	Nephrologisches Zentrum	Villingen-Schwenningen
Germany	Heinrich Braun Klinikum	Zwickau

Sponsors (2)

Lead Sponsor	Collaborator
Technische Universität Dresden	Kaneka Pharma Europe N.V.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Reduction of individual endpoints	Reduction of individual endpoints at the final visit, reported as % reduction of the number of cumulated and individual events; death from any cause,; CHD death,; CV death,; MI,; documented unstable angina that requires admission into a hospi-tal,; all coronary revascularization occurring at least 30 days after a prior MACE event: either PCI or; CABG; all revascularization (including both coronary and non-coronary) occurring at least 30 days after a prior MACE event,; in-stent restenosis rate,; stroke,; transient ischemic attack,; Percentage of subjects achieving a mean reduction of Lp(a) of 60% or more; Mean reduction of Lp(a); Percentage of subjects achieving mean LDL-C reduction of 60 % or more; Number of apheresis related side effects; Quality of life	2 years of follow-up
Primary	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	An at least 10 % reduction of the proportion of events	An at least 10 % reduction of the proportion of events regarding the composite endpoint of cardiovascular death, major coronary event, cerebrovascular accidents and stroke.	2 years of follow-up
Secondary	An at least 10 % reduction of the proportion of events	An at least 10 % reduction of the proportion of events regarding the composite endpoint of cardiovascular death, major coronary events and all cerebrovascular events.	2 years of follow-up
Secondary	An at least 10 % reduction of the proportion of events regarding the composite Secondary endpoints of the Trial	An at least 10 % reduction of the proportion of events regarding the composite endpoint of CV death, non-fatal MI, documented unstable angina that requires admission into a hospital, all revascularization (including both coronary and non-coronary) occurring at least 30 days after the MACE event, the rate of in-stent restenosis and non-fatal stroke.	2 years of follow-up

External Links

•   Study Homepage