Personalised Therapeutics @LUMC (PT@LUMC)

Personalised Therapeutics @ Leiden University Medical Center

In PT@LUMC 2000 patients will be randomized between a PGx-guided dosing group and a standard of care group. The patients will be followed for one year in which they will be asked to report adverse drug reactions at one, three, six and twelve months.

Study Overview

• Status: Active, not recruiting
• Conditions: Adverse Drug Reaction
• Intervention / Treatment: Genetic: Genetic test for 14 pharmacogenes

Detailed Description

Rationale: Pharmacogenomics (PGx) is the study of genetic variability affecting an individual's response to a drug. PGx is a critical component of personalized medicine. Currently, PGx is applied for individual drugs and/or individual genetic variants. Recently a pre-emptive panel-based approach was proposed including 48 PGx variants covering 13 genes for which the Dutch Pharmacogenetic Working Group (DPWG) has issued evidence based drug dosing guidelines. The PGx panel contains all genetic variants that are considered actionable by the DPWG i.e. requiring a dose adjustment or switch to another drug. Interestingly, more than 95% of the Dutch population carries one or more actionable genotype(s) for one of the genes covered by this panel and 10% carries 4 or more. Based upon national prescription data we estimate that 5.6% of all first prescriptions would require an individualization of the dose or drug. However, in current clinical practice the potential of PGx testing is not fully exploited and the impact for LUMC is unknown. Therefore a prospective study on pre-emptive PGx testing will be performed in the LUMC. In this study 2.000 patients will be randomized to PGx-guided dosing or standard of care.

In addition, we plan to conduct sub-studies with the obtained data. The first study aims to explore novel associations of genetic variants with variability in drug response. The second aims to explore the impact of concomitant medication and other non-genetic factors on pharmacogenetic associations in a pragmatic setting.

Primary objective: To implement pre-emptive panel based PGx testing in the LUMC and determine patient benefit of PGx guided drug prescription and dispensing.

Study design: A prospective, open, randomized study in 2,000 patients with a duration of 2 years.

Study population: Patients over 18 years old undergoing medication verification in the LUMC.

Study procedure: Patients are randomized to PGx-guided dosing or standard of care. The PGx-guided group receives pre-emptive PGx testing for a panel of 14 genes (including 227 PGx variants) followed by personalized drug and dose recommendations for newly prescribed drugs. Recommendations are based on the guidelines of the Dutch Pharmacogenetics Working Group. Patients in the control group will receive usual drug prescriptions, without PGx-guided drug or dose selection.

Main study parameters/endpoints: The primary outcome is the occurrence of drug-genotype associated adverse drug reactions (ADR) in the first 12 months following the genetic test. The outcome is dichotomized at ≥ grade 3 CTC-AE.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness. Participation in this study carries a small extra burden:

1) 10 ml additional blood will be collected during a venipuncture that is planned as part of regular treatment. 2) to complete an online questionnaires at one, three, six and twelve months. No extra visits to the clinic are necessary. Benefits to patients in the study arm include a potentially reduced risk of ADRs. All patients will receive their pharmacogenetic profile which can be used to individualize drug treatment based on the DPWG guidelines. Overall, minimal risks are expected for included patients due to the fact that all of the drugs included within this study have previously been licensed for routine use and thus have been evaluated as having a positive benefit/risk ratio. The DPWG guidelines are based on systematic review of the literature, have been published in peer-reviewed journals and are commonly accepted.

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

Study Locations

• Netherlands
  • Zuid Holland
    • Leiden, Zuid Holland, Netherlands, 2333ZA
      • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

All patients of 18 years of age or older that participate in medication verification in the LUMC are eligible to participate.

Description

Inclusion Criteria:

• Provision of informed consent (IC) prior to any study specific procedures.
• Be aged ≥18
• A venapunction as part of routine treatment
• Receive a medication verification interview
• Be able and willing to be followed-up for at least one year

Exclusion Criteria:

• Pregnancy or lactating
• Previous participation in the PREPARE trial (NCT03093818, NL60069.058.16)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PGx-guided dosing; This group will be genotyped for 14 pharmacogenes at the start of the study.	Genetic: Genetic test for 14 pharmacogenes; Genotyping with the Global Diversity Array-8 v1.0 BeadChip with enhanced PGx
Standard of care; This group will be genotyped for 14 pharmacogenes at the end of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADRs grade >3 total	The primary outcome will be the occurrence of clinically relevant (classified as NCI-CTCAE grade 3, 4, or 5) patient reported ADRs within one year of follow-up.	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADRs grade >3	The occurrence of clinically relevant (classified as NCI-CTCAE grade 3, 4, or 5) patient reported ADRs, attributable to a PGx drug, at one, three, six and twelve months of follow-up.	One, three, six and twelve months
Acceptance to recommendations	Acceptance of the recommendations measured by comparing the number of dose adjustments and medication switches in the study and control arm.	One year
Cost-effectiveness	The cost-effectiveness of a pre-emptive PGx panel test will be analysed by relating healthcare costs (including genetic testing, drugs and ADR-related care) to quality-adjusted life years (estimated using the EQ-5D-5L).	One year
ADRs grade >2 total	The occurrence of clinically relevant (classified as NCI-CTCAE grade 2, 3, 4, or 5) patient reported ADRs, attributable to a PGx drug, within one year of follow-up.	One year
ADRs grade >2	The occurrence of clinically relevant (classified as NCI-CTCAE grade 2, 3, 4, or 5) patient reported ADRs, attributable to a PGx drug, at one, three, six and twelve months of follow-up.	One, three, six and twelve months
Frequency of PGx drug prescriptions	The frequency of PGx drug prescriptions (per PGx gene) (corrected for dose changes due to PGx outcome) within one year of follow-up.	One year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of drugs per patient.		One year
The number of ADRs per patient ≥ grade 3.		One year
The number of ADRs per patient ≥ grade 2.		One year
The number of dose adjustment based on PGx guidelines.		One year
The total number of actionable PGx genes per patients.		One year
The total number of PGx drugs per patient.		One year
The treatment effectivity via routine drug levels (only those that are collected routinely) as a proxy for exposure.	Depending on the drug a different level (higher or lower) provides information regarding the treatment	One year
Patient-reported drug adherence.	Drug adherence will be questioned during the study, the different moments will be compared and the overall drug adherence in the study will be addressed. A lower answer indicates less drug adherence and a higher score better drug adherence.	One year

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: bio.logis digital health GmbH

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: August 18, 2022
• First Submitted That Met QC Criteria: August 18, 2022
• First Posted (Actual): August 19, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Pharmacogenetics
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions
• Other Study ID Numbers: NL78161.058.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No