Clinical trial NCT02791802: Effect of Lipoprotein(a) Elimination by Lipoprotein Apheresis on Cardiovascular Outcomes
Official title: A European Multicenter Study on the Effect of Lipoprotein(a) Elimination by Lipoprotein Apheresis on Cardiovascular Outcomes
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Lipoprotein Types--Lp System Lp(A) Hyperlipoproteinemia
Keywords: Lipoprotein(a)
lipoprotein/lipid apheresis
CV disease
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
Collaborators: name: Kaneka Pharma Europe N.V.
First posted: 2016-06-07
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


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

Primary outcomes:
measure: The primary end-point is an at least 10 % reduction of the proportion of events
timeFrame: 2 years of follow-up
Secondary outcomes:
measure: An at least 10 % reduction of the proportion of events
timeFrame: 2 years of follow-up
measure: An at least 10 % reduction of the proportion of events
timeFrame: 2 years of follow-up
measure: An at least 10 % reduction of the proportion of events regarding the composite Secondary endpoints of the Trial
timeFrame: 2 years of follow-up
Other outcomes:
measure: Reduction of individual endpoints
timeFrame: 2 years of follow-up
Locations:
city: Dresden
country: Germany
facility: University Hospital Carl Gustav Carus
state: Saxony
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW Universitätsklinik der Ruhr-Universität Bochum Klinik für Kardiologie
city: Bochum
country: Germany
facility: Dialyse am Kortumpark
city: Göttingen
country: Germany
facility: Nephrologisches Zentrum Göttingen
city: Meißen
country: Germany
facility: PHV Dialysezentrum
city: Muenchen
country: Germany
facility: Klinikum der Universität München Campus Innenstadt
city: Muenchen
country: Germany
facility: Klinikum der Universität München Campus Großhadern
city: Potsdam
country: Germany
facility: Dialysezentrum Potsdam
city: Reinbek
country: Germany
facility: Nierenzentrum Reinbek
city: Rostock
country: Germany
facility: Nephrocare Rostock GmbH Medizinisches Versorgungszentrum Südstadt
city: Villingen-Schwenningen
country: Germany
facility: Nephrologisches Zentrum
city: Zwickau
country: Germany
facility: Heinrich Braun Klinikum
Study officials:
affiliation: Technische Universität Dresden
name: Bernd Hohenstein, MD
role: PRINCIPAL_INVESTIGATOR
References: