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

Technische Universität Dresden

Status: Unknown

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

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT02791802

TUD-LPA16-001

Details and patient eligibility

About

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.

Enrollment: 1,000 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

1,000 participants in 2 patient groups

Group A: Lipoprotein apheresis subjects

Description:

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

Description:

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.