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

• Conditions: Lipoprotein Types--Lp System Lp(A) Hyperlipoproteinemia

• Registration Number: NCT02791802
• Lead Sponsor: Technische Universität Dresden

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-05-26
• Study First Submitted QC: 2016-06-06
• Study First Posted: 2016-06-07
• Study Start: 2016-08
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-29
• Last Update Posted: 2022-05-02
• Primary Completion: 2022-12
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1000

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary end-point is an at least 10 % reduction of the proportion of events	2 years of follow-up	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.

Secondary Outcome Measures

Name	Time	Method
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 endpoint of cardiovascular death, major coronary events and all cerebrovascular events.
An at least 10 % reduction of the proportion of events regarding the composite Secondary endpoints of the Trial	2 years of follow-up	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.

Trial Locations

Locations (12)

Nephrologisches Zentrum Göttingen; 🇩🇪 Göttingen, Germany

University Hospital Carl Gustav Carus; 🇩🇪 Dresden, Saxony, Germany

Herz- und Diabeteszentrum NRW Universitätsklinik der Ruhr-Universität Bochum Klinik für Kardiologie; 🇩🇪 Bad Oeynhausen, Germany

Nephrocare Rostock GmbH Medizinisches Versorgungszentrum Südstadt; 🇩🇪 Rostock, Germany

Dialyse am Kortumpark; 🇩🇪 Bochum, Germany

PHV Dialysezentrum; 🇩🇪 Meißen, Germany

Klinikum der Universität München Campus Innenstadt; 🇩🇪 Muenchen, Germany

Dialysezentrum Potsdam; 🇩🇪 Potsdam, Germany

Klinikum der Universität München Campus Großhadern; 🇩🇪 Muenchen, Germany

Nierenzentrum Reinbek; 🇩🇪 Reinbek, Germany

Nephrologisches Zentrum; 🇩🇪 Villingen-Schwenningen, Germany

Heinrich Braun Klinikum; 🇩🇪 Zwickau, Germany