Personalised Hyperlipidaemia Therapies Guided by Pharmacogenomics

Not Applicable

Not yet recruiting

• Conditions: Cardiovascular Diseases
• Interventions: Other: Pharmacogenomics-directed Hyperlipidaemia Management

• Registration Number: NCT06217523
• Lead Sponsor: National University of Singapore

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2023-11-06
• Study First Submitted QC: 2024-01-19
• Study First Posted: 2024-01-22
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-26
• Last Update Posted: 2024-03-27
• Study Start: 2024-04
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 700

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention Group	Pharmacogenomics-directed Hyperlipidaemia Management	Pharmacist-guided care; dosing of statin medication based on genetic information

Primary Outcome Measures

Name	Time	Method
Incidence of myopathy complaints	6 months	Incidence of myopathy complaints at 1-month, 3-month, and 6-month
Changes in LDL-C, HDL-C, Total cholesterol, and Triglycerides	12 months	Changes in LDL-C, HDL-C, Total cholesterol, and Triglycerides over 12 months
Change in creatine kinase	6 months	Changes in creatine kinase from baseline to six months only if myopathy complaints were present.

Secondary Outcome Measures

Name	Time	Method
(Clinician or Prescriber) Adherence to recommendations	6 months	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
Healthcare utilisation	12 months	Healthcare utilisation will be measured as the number of visits over 12 months
Changes in health-related quality of life	12 months	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.
Direct medical costs	12 months	Total direct medical costs measured in USD will be computed from consultation costs, laboratory costs, and visits to other healthcare professionals.
Cost effectiveness analysis	12 months	Cost effectiveness analysis will be measured as total direct medical cost per disability-adjusted life year
Changes to beliefs about medications	12 months	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