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Completed

NCT Number: NCT03604471

Lipid-lowering Therapy Individualization

This clinical study will explore individual factors influencing statin pharmacokinetics in a cohort of 150 patients treated with atorvastatin.

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Key information

Conditions

Hypercholesterolemia Dyslipidemias Hyperlipidemias Lipid Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Cliniques universitaires Saint-Luc

Brussels, 1200, Belgium

About this study

Atorvastatin is widely prescribed for the treatment of hypercholesterolemia to prevent the risk of cardiovascular diseases, a leading death cause in industrialized countries. There exists considerable inter-individual variability in response to statins, reflected by differences in lipid-lowering effect or risk of presenting adverse drug reaction; mainly myotoxicity. A plethora of different factors (demographic, genetic, physiopathologic, environmental...) have been tested to explain this variability but it lacks of pharmacokinetic (PK) data and/or replications of observations are rare and results remain inconclusive, probably because of non-adapted designs and no-clear driven-hypothesis but also due to a lack of scientific rationale and deep mechanistic understanding. This clinical study will explore individual factors influencing statin PK in a cohort of 150 patients treated with atorvastatin. The collection of meticulous clinical PK data and a rigorous statistical analysis will allow quantifying the effect of each identified parameter on statin PK and eventually, defining a population-based PK model taking into account the combined effect of all covariates in a quantitative approach. This innovative prospectively designed clinical study will ultimately allow predicting atorvastatin PK fluctuations and anticipating any inadequate dosing in clinical care.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Treatment with atorvastatin (any dose)

Exclusion criteria

  • Unable to provide informed consent

Treatment and study plan

atorvastatin

Drug

Blood sampling for atorvastatin quantification and pharmacogenetic analysis.

Primary outcomes

  1. Atorvastatin population pharmacokinetics

    Time frame: 18 months

    Concentrations of atorvastatin acid (pmol/ml) will be measured by HPLC-MS using sparse samples obtained over the entire study period. Data will be pooled and analyzed using population pharmacokinetic modeling. The reported pharmacokinetic parameters will depend on the type of model that best fits the data.

  2. Atorvastatin metabolites population pharmacokinetics

    Time frame: 18 months

    Concentrations of ortho-hydroxyatorvastatin (pmol/ml), para-hydroxyatorvastatin (pmol/ml) and atorvastatin lactone (pmol/ml) will be measured by HPLC-MS using sparse samples obtained over the entire study period. Data will be pooled and analyzed using population pharmacokinetic modeling. The reported pharmacokinetic parameters will depend on the type of model that best fits the data.

Secondary outcomes

  1. Cholesterol

    Time frame: 18 months

    Measurement of total cholesterol, LDL cholesterol and HDL cholesterol at each visit

  2. Creatine kinase

    Time frame: 18 months

    Measurement of creatine kinase at each visit

  3. Occurrence of adverse drug events

    Time frame: 18 months

    Reports of adverse drug events will be recorded at each visit using a standardized questionnaire that includes the following categories : muscle cramps (grade 1 to 5), muscle pain (graded 1 to 5), rhabdomyolysis, gastro-intestinal side effects (Nauseas, diarrhea or vomitus), other side effects.

  4. Pharmacogene genotype

    Time frame: 18 months

    Patients will be genotyped for single nucleotide polymorphisms of interest in the following genes : ABCB1, ABCC1, ABCC2, ABCC4, ABCC5, ABCG2, CYP3A4, CYP3A5, NR1I2, POR, PPARalpha, SLCO1B1, SLCO2B1, SLCO3A1.

  5. Triglycerides

    Time frame: 18 months

    Measurement of triglyceride levels at each visit

Sponsors and collaborators

Lead sponsor

Université Catholique de Louvain

Other

Collaborators

  • Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Registry information

Important dates

Study start
2017
Primary completion
2019
Study completion
2019
First posted
Jul 27, 2018
Registry last updated
Sep 3, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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