To describe the characteristics of patients with either low PCSK9 inhibitor therapy efficacy or adverse effects.
ID
Source
Brief title
Condition
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are differences in clinical parameters (e.g., patient
anthropometrics between patients and controls, mutations in the PCSK9 gene
possibly interfering with PCSK9 inhibitor therapy, variants in other lipid
metabolism or PCSK9 related genes, gene expression, (semi)quantification of
proteins (PCSK9 protein, other proteins involved in lipid metabolism,
proteomics), (semi-)quantification of metabolites (e.g. lipids/fatty acids).
Secondary outcome
nvt
Background summary
High plasma levels of Low Density Lipoprotein-cholesterol (LDL-C) result in
increased cardiovascular risk. Monoclonal antibodies against proprotein
convertase subtilisin/kexin type 9 (PCSK9) have been shown to result in LDL-C
lowering and CVD risk reduction. This relatively new class of drugs has not
been widely studied in daily clinic, and anecdotal evidence has suggested that
a small proportion of patients do either not respond to this medication or
suffer from side effects.
Study objective
To describe the characteristics of patients with either low PCSK9 inhibitor
therapy efficacy or adverse effects.
Study design
Multi-center case-control study, in which blood samples will be collected at
two different time-points. One sample when patient is on therapy, one sample
when patient is off therapy.
Study burden and risks
Blood will be collected from participants by venous blood sampling on two
occasions (86 ml total). Patients in whom therapy fails will be subjected to a
washout period of 6 weeks of PCSK9 inhibitor therapy before restarting PCSK9
inhibitor therapy as a re-challenge. This washout period and a re-challenge are
normal clinical practice and are not part of this study. Only the collection of
blood samples is part of this study. The period without PCSK9-inhibitor therapy
is not deemed a clinical risk, as these patients were shown not to respond to
the PCSK9 antibody therapy prior to enrolment.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Patients
- On therapy or discontinued therapy with alirocumab 75mg 1x/2weeks or 150mg
1x/2weeks, or with evolocumab 140mg 1x/2weeks.
- Failure of PCSK9 inhibitor therapy, due to adverse effects leading to
discontinuation of the drug
OR
- Failure of PCSK9 inhibitor therapy, due to less than 30 percent reduction in
LDL-C observed by the referring physician
- >18 years of age, Controls:
- On therapy with alirocumab or with evolocumab
- On therapy with alirocumab or with evolocumab
- No adverse effects leading to discontinuation of the drug
- LDL-C reduction above 30 percent., - >18 years of age.
Exclusion criteria
None
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL66234.018.18 |