NCT03093818

Brief Summary

PREPARE is an international, prospective, multi-center, open, randomized, cross-over implementation study assessing the impact of pre-emptive pharmacogenomic testing, of a panel of actionable pharmacogenomic variants, on adverse event incidence. Additional outcomes include, healthcare expenditure, process indicators for implementation and provider adoption of pharmacogenomics.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6,950

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Mar 2017

Longer than P75 for not_applicable

Geographic Reach
7 countries

7 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 6, 2017

Completed
14 days until next milestone

Study Start

First participant enrolled

March 20, 2017

Completed
8 days until next milestone

First Posted

Study publicly available on registry

March 28, 2017

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2020

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2021

Completed
Last Updated

April 19, 2024

Status Verified

April 1, 2024

Enrollment Period

3.5 years

First QC Date

March 6, 2017

Last Update Submit

April 17, 2024

Conditions

Adverse Drug Reaction

Outcome Measures

Primary Outcomes (1)

  • Occurrence of a clinically relevant adverse drug reaction which is caused by the drug of inclusion. For oncology patients only hematological toxicities (grade 4-5) and non-hematological toxicities (grade 3-5) will be considered clinically relevant.

    Defined as an adverse drug reaction which is causally related to the drug of inclusion (definite, probable or possible), clinically relevant (CTCAE Grade 2,3,4 or 5) and associated with a drug-genotype interaction (as per the Dutch Pharmacogenomics Working Group guidelines)

    12 weeks

Secondary Outcomes (7)

  • Physician and pharmacist adherence to Dutch Pharmacogenomics Working Group guidelines

    18 months

  • Healthcare expenditure related to adverse events

    18 months

  • Incidence of drug discontinuation due to an adverse event

    18 months

  • Incidence of discontinuation due to lack of efficacy

    18 months

  • Quality of life

    18 months

  • +2 more secondary outcomes

Study Arms (2)

Pharmacogenomic testing arm

EXPERIMENTAL

4,050 patients will provide a DNA sample. A pharmacogenomic test is performed. Results of this test are incorporated in the (electronic) medical record and combined with a clinical decision support system. Physicians and pharmacists may choose to use these results to guide drug and dose selection as per the Dutch Pharmacogenomics Working Group guidelines. Patients will receive a "Safety-Code card" containing their personal pharmacogenomics results, which can be used by other physicians or pharmacists during subsequent prescriptions.

Other: Pharmacogenomic testing

Standard of care arm

NO INTERVENTION

4,050 patients will provide a DNA sample. However, no pharmacogenomic test is performed until the study is completed. Physicians and pharmacists will prescribe and dispense drugs routinely, without using pharmacogenomic test results to guide drug and dose selection. Patients will receive a mock "Safety-Code card", which does not contain personal pharmacogenomics results.

Interventions

Pharmacogenomic testingOTHER

The pharmacogenomic panel to be used incorporates 48 genetic variants for the following 13 "pharamacogenes": CYP2B6 (cytochrome P450), CYP2C19, CYP2C9, CYP2D6,CYP3A4, DPYD (dihydropyrimidine dehydrogenase), FVL (factor five Leiden), HLA-B (human leukocyte antigen), NUDT15 (Nudix hydrolase), SLCO1B1 (solute carrier organic anion transporter), TPMT (thiopurine methyltransferase), UGT1A1 (UDP-glucuronosyltransferase), and VKORC1 (vitamin K epoxide reductase complex).

Pharmacogenomic testing arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Subject must be ≥ 18 years old
  • Subject must receive a first prescription (meaning no known prescription for this drug in the preceding 12 months) for one or more of 42 drugs, for which a Dutch Pharmacogenomic Working Group guideline is available, which is prescribed to them in routine care
  • Subject is able and willing to take part and be followed-up for at least 12 weeks
  • Subject is able to donate blood or saliva
  • Subject has signed informed consent
  • The study limit of enrolment (200 per arm, per 18-month block) for that drug has not been reached

You may not qualify if:

  • Subject is pregnant or lactating
  • Subject has a life expectancy estimated to be less than three months by treating clinical team
  • For inpatients: hospital admission is expected to be less than 72 hours
  • Subject is unable to consent to the study
  • Subject is unwilling to take part
  • Subject has no fixed address
  • Subject has no current general practitioner
  • Subject is, in the opinion of the Investigator, not suitable to participate in the study
  • Subject has existing impaired hepatic or renal function for which a lower dose or alternate drug selection are already part of current routine care. This would not apply to any drugs specifically given to manage liver/renal impairment/transplantation.
  • Subject has an estimated glomerular filtration rate (MDRD) of less than 15 ml/min per 1,73m2 in a subject with a functioning graft
  • Subject has advanced liver failure (stage Child-Pugh C)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Medical University of Vienna

Vienna, Austria

Location

University of Patras

Pátrai, Greece

Location

Centro di Riferimento Oncologico

Aviano, Italy

Location

Leiden University Medical Center

Leiden, Netherlands

Location

University of Ljubljana

Ljubljana, Slovenia

Location

Servicio Andaluz de Salud

Granada, Spain

Location

University of Liverpool

Liverpool, United Kingdom

Location

Related Publications (4)

  • Habtemariam HD, Guchelaar HJ, Manson LEN, Swen JJ, Kant AC, Bohringer S. Reporting Adverse Drug Events: A Comparison of an Online Patient Tool Versus Telephone-Based Monitoring in Community Pharmacy Patients in the Netherlands. Drug Saf. 2025 Nov;48(11):1205-1214. doi: 10.1007/s40264-025-01571-4. Epub 2025 Jun 14.

    PMID: 40517185DERIVED

  • Roncato R, Bignucolo A, Peruzzi E, Montico M, De Mattia E, Foltran L, Guardascione M, D'Andrea M, Favaretto A, Puglisi F, Swen JJ, Guchelaar HJ, Toffoli G, Cecchin E. Clinical Benefits and Utility of Pretherapeutic DPYD and UGT1A1 Testing in Gastrointestinal Cancer: A Secondary Analysis of the PREPARE Randomized Clinical Trial. JAMA Netw Open. 2024 Dec 2;7(12):e2449441. doi: 10.1001/jamanetworkopen.2024.49441.

    PMID: 39641926DERIVED

  • Swen JJ, van der Wouden CH, Manson LE, Abdullah-Koolmees H, Blagec K, Blagus T, Bohringer S, Cambon-Thomsen A, Cecchin E, Cheung KC, Deneer VH, Dupui M, Ingelman-Sundberg M, Jonsson S, Joefield-Roka C, Just KS, Karlsson MO, Konta L, Koopmann R, Kriek M, Lehr T, Mitropoulou C, Rial-Sebbag E, Rollinson V, Roncato R, Samwald M, Schaeffeler E, Skokou M, Schwab M, Steinberger D, Stingl JC, Tremmel R, Turner RM, van Rhenen MH, Davila Fajardo CL, Dolzan V, Patrinos GP, Pirmohamed M, Sunder-Plassmann G, Toffoli G, Guchelaar HJ; Ubiquitous Pharmacogenomics Consortium. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study. Lancet. 2023 Feb 4;401(10374):347-356. doi: 10.1016/S0140-6736(22)01841-4.

    PMID: 36739136DERIVED

  • Psarias G, Iliopoulou E, Liopetas I, Tsironi A, Spanos D, Tsikrika A, Kalafatis K, Tarousi D, Varitis G, Koromina M, Siamoglou S, Patrinos GP. Development of Rapid Pharmacogenomic Testing Assay in a Mobile Molecular Biology Laboratory (2MoBiL). OMICS. 2020 Nov;24(11):660-666. doi: 10.1089/omi.2020.0168. Epub 2020 Oct 16.

    PMID: 33064577DERIVED

Related Links

MeSH Terms

Conditions

Drug-Related Side Effects and Adverse Reactions

Interventions

Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Genetic TestingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisInvestigative TechniquesGenetic TechniquesGenetic ServicesHealth ServicesHealth Care Facilities Workforce and ServicesDiagnostic ServicesPreventive Health Services

Study Officials

  • Jesse J. Swen, PharmD PhD

    Leiden University Medical Center

    PRINCIPAL INVESTIGATOR

  • Munir Pirmohamed, MB ChB(Hons) PhD

    University of Liverpool

    PRINCIPAL INVESTIGATOR

  • Gere Sunder-Plassmann, MD

    Medical University of Vienna

    PRINCIPAL INVESTIGATOR

  • Giuseppe Toffoli, MD

    Centro di Riferimento Oncologico

    PRINCIPAL INVESTIGATOR

  • Cristina Lucía Dávila Fajardo, PharmD PhD

    Andaluz Health Service

    PRINCIPAL INVESTIGATOR

  • George P. Patrinos, PhD

    University of Patras

    PRINCIPAL INVESTIGATOR

  • Vita Dolzan, MD PhD

    University of Ljubljana

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
A 10% random sample will be re-assessed for causality and severity of recorded ADE will by a second independent, blinded (unaware of patient allocation) assessor. Drug-genotype association of the ADE as per the Dutch Pharmacogenomics Working Group guideline will be assessed by a blinded review committee
Purpose
PREVENTION
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Associate Professor of Pharmacogenetics, Section Chair Laboratory, Department of Clinical Pharmacy and Toxicology

Study Record Dates

First Submitted

March 6, 2017

First Posted

March 28, 2017

Study Start

March 20, 2017

Primary Completion

September 30, 2020

Study Completion

May 1, 2021

Last Updated

April 19, 2024

Record last verified: 2024-04

Data Sharing

IPD Sharing
Will share

The data management plan has been written to comply to FAIR principles. Findable: We will indicate the existence of the data in our scientific publications and at our website (www.upgx.eu). Accessible: The datasets will not be made openly accessible, but will become available upon request after publications of the main paper by the U-PGx consortium. Interoperable: We will make use of standardized scores and standardized methodologies for example the star allele nomenclature and rs-numbering for genetic variants. Reusable: We do not intend to licence our data. A data dictionary is available for the entire eCRF.

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
Time Frame
The datasets will not be made openly accessible, but will become available upon request after publications of the main paper by the U-PGx consortium.
Access Criteria
Requests to re-use the data sets by third parties will be addressed to U-PGx Executive Board including the coordinator, i.e. Leiden University Medical Center, the Netherlands.
More information

Locations

GB(1)GR(1)ES(1)NL(1)SL(1)AU(1)IT(1)