Personalised Therapeutics @LUMC

Adverse Drug Reaction Clinical Trial

— PT@LUMC  

Official title:

Personalised Therapeutics @ Leiden University Medical Center

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05508763
• Other study ID #: NL78161.058.21
• Status: Recruiting
• Start date: December 1, 2022
• Est. completion date: October 2024

Study information

• Verified date: May 2023
• Source: Leiden University Medical Center
• Contact: Jesse Swen, PharmD
• Phone: 0715263136
• Email: j.j.swen[@]lumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: October 2024
• Est. primary completion date: September 2024
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Adverse Drug Reaction
• Drug-Related Side Effects and Adverse Reactions

Intervention

Genetic:
• Genetic test for 14 pharmacogenes
Genotyping with the Global Diversity Array-8 v1.0 BeadChip with enhanced PGx

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden	Zuid Holland

Sponsors (2)

Lead Sponsor	Collaborator
Leiden University Medical Center	bio.logis digital health GmbH

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The number of drugs per patient.		One year
Other	The number of ADRs per patient = grade 3.		One year
Other	The number of ADRs per patient = grade 2.		One year
Other	The number of dose adjustment based on PGx guidelines.		One year
Other	The total number of actionable PGx genes per patients.		One year
Other	The total number of PGx drugs per patient.		One year
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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