Personalised Hyperlipidaemia Therapies Guided by Pharmacogenomics

National University of Singapore700 enrolled

Overview

This trial aims to evaluate the impact of clinical pharmacists' pharmacogenomics-guided choice and statin titration for managing hyperlipidaemia. The central hypotheses of this trial are (1) clinical pharmacists' pharmacogenomics-guided choice and titration of statins will lead to a more significant reduction in LDL-c; (2) lower incidence of myopathies with the use of statins for hyperlipidaemia management over 12 months compared to usual care by doctors alone. Active follow-up and titration should occur over the first six months. However, the participants will be followed up to 12 months to confirm the sustained LDL level attainment.

The primary aims are: * The changes in Low-Density Lipoprotein cholesterol (LDL-c), total cholesterol, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-c) levels, and * The incidence of myopathies over 12 months. The secondary aims include: * Characterisation of the pharmacogenomic relationship between serum levels of statins (and their metabolites) with the changes in LDL-c levels and incidence of myopathies over six months * Economic outcomes include but are not limited to the cost-effectiveness of pharmacogenomic testing in attaining LDL-c targets * Change in health-related quality of life over 12 months is measured using the EuroQoL 5-Dimension 5-Level questionnaire

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

700

Conditions

Cardiovascular Diseases

Eligibility

Sex: ALLMin age: 21 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participants between 21 and 75 years old * Participants who are planning to start on statin\* medication or whose LDL-c goals have not been met, per Appendix B. * Participants who are able to communicate in English, Chinese or Malay. Participants who are planning to start or will be started on the following doses are eligible: atorvastatin 10-80 mg/day, rosuvastatin 10-40 mg/day, or simvastatin 10-40 mg/day within the last two to four weeks before enrolment Exclusion Criteria: * Participants who are statin-intolerant or in whom statins are contraindicated * Participants on a statin dosing schedule of every other day (EOD) * Participants administered on potent Cytochrome P450 3A4 (CYP3A4) or Cytochrome P450 2C9 (CYP2C9) or OATP inhibitors or inducers. * Participants on evolocumab and alirocumab prior to enrolment * Participants with documented diagnosis of psychiatric conditions * Participants requiring palliative care, end-of-life care, or those with a life expectancy of less than one year * Pregnant and lactating women * Participants with complaints of myalgia or muscle weakness at baseline, before the commencement of statin * Participants who are unable to swallow a whole statin tablet

Outcomes

Primary Outcomes

Changes in LDL-C, HDL-C, Total cholesterol, and Triglycerides

Changes in LDL-C, HDL-C, Total cholesterol, and Triglycerides over 12 months

Time frame: 12 months

Change in creatine kinase

Changes in creatine kinase from baseline to six months only if myopathy complaints were present.

Time frame: 6 months

Incidence of myopathy complaints

Incidence of myopathy complaints at 1-month, 3-month, and 6-month

Time frame: 6 months

Secondary Outcomes

(Clinician or Prescriber) Adherence to recommendations

The proportion of patients whose statin dose was prescribed in adherence to SLCO1B1 and/or ABCG2 phenotype recommendations, the proportion of patients with lipid-lowering drug changes following phenotype results, retrospective exploratory analyses of emerging gene predictors of lipid-control and myopathy

Time frame: 6 months

Cost effectiveness analysis

Cost effectiveness analysis will be measured as total direct medical cost per disability-adjusted life year

Time frame: 12 months

Direct medical costs

Total direct medical costs measured in USD will be computed from consultation costs, laboratory costs, and visits to other healthcare professionals.

Time frame: 12 months

Healthcare utilisation

Healthcare utilisation will be measured as the number of visits over 12 months

Time frame: 12 months

Changes in health-related quality of life

Changes in health-related quality of life will be measured using the utility score derived from EQ-5D-5L over 12 months. An improvement in scores imply a better quality of life.

Time frame: 12 months

Changes to beliefs about medications

Drug-Associated Risk Tool (DART)-Beliefs about Medicines Questionnaire (BMQ) scores will be computed. It is expected for responses to become more favourable over time

Time frame: 12 months

Personalised Hyperlipidaemia Therapies Guided by Pharmacogenomics

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts