PREemptive Pharmacogenomic Testing for Preventing Adverse Drug REactions
NCT ID: NCT03093818
Last Updated: 2024-04-19
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
NA
6950 participants
INTERVENTIONAL
2017-03-20
2021-05-01
Brief Summary
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Detailed Description
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Patients are eligible for participation when they receive a first prescription for one or more of 39 drugs for which a Dutch Pharmacogenomic Working Group guideline is available (acenocoumarol, amitriptyline, aripiprazole, atomoxetine, atorvastatin, azathioprine ,capecitabine, citalopram, clomipramine, clopidogrel, codeine, doxepin, efavirenz, escitalopram, flecainide, flucloxacillin, fluorouracil, haloperidol, imipramine, irinotecan, mercaptopurine, metoprolol, nortryptiline, paroxetine, phenprocoumon, phenytoin, pimozide, propafenon, sertraline, simvastatin, tacrolimus, tamoxifen, tegafur, thioguanine, tramadol, venlafaxine, voriconazole, warfarin or zuclopenthixol). All patients will be followed for a minimum of three months and a maximum of 18 months. In total, 8,100 patients will be recruited; 4,050 will receive pharmacogenomic testing, and 4,050 will receive standard of care. Each implementation site will concentrate on, but is not limited to, recruiting patients within a specific therapeutic area. Therapeutic areas include primary care, general medicine, cardiology, oncology, psychiatry, neurology, and transplantation. It is hypothesized that implementing pharmacogenomics guided drug and dose selection will decrease incidence of clinically relevant adverse drug reactions by 30% (from 4% to 2.8% among those with actionable drug-gene interactions).
Conditions
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Study Design
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RANDOMIZED
CROSSOVER
PREVENTION
SINGLE
Drug-genotype association of the ADE as per the Dutch Pharmacogenomics Working Group guideline will be assessed by a blinded review committee
Study Groups
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Pharmacogenomic testing arm
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.
Pharmacogenomic testing
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).
Standard of care arm
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.
No interventions assigned to this group
Interventions
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Pharmacogenomic testing
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).
Eligibility Criteria
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Inclusion Criteria
* 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
Exclusion Criteria
* Subject is pregnant or lactating
* Subject has a life expectancy estimated to be less than three months by treating clinical team
* Duration of the drug of inclusion total treatment length is planned to be less than seven consecutive days. A drug whose route of administration changes during the first seven days (e.g. intravenous to oral flucloxacillin) but whose total treatment duration is seven days or longer, is still eligible.
* 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)
18 Years
ALL
No
Sponsors
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University of Liverpool
OTHER
Medical University of Vienna
OTHER
Centro di Riferimento Oncologico - Aviano
OTHER
Andaluz Health Service
OTHER_GOV
University of Patras
OTHER
University of Ljubljana
OTHER
Karolinska Institutet
OTHER
The Golden Helix Foundation
UNKNOWN
Royal Dutch Pharmacists Association (KNMP)
UNKNOWN
Bio.Logis Genetic Information Management
UNKNOWN
University Paul Sabatier of Toulouse
OTHER
Uppsala University
OTHER
Robert Bosch Gesellschaft für Medizinische Forschung mbH (RBMF)
OTHER
Federal Institute for Drugs and Medical Devices
UNKNOWN
St. Antonius Hospital
OTHER
J.J.Swen
OTHER
Responsible Party
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J.J.Swen
Associate Professor of Pharmacogenetics, Section Chair Laboratory, Department of Clinical Pharmacy and Toxicology
Principal Investigators
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Jesse J. Swen, PharmD PhD
Role: PRINCIPAL_INVESTIGATOR
Leiden University Medical Center
Munir Pirmohamed, MB ChB(Hons) PhD
Role: PRINCIPAL_INVESTIGATOR
University of Liverpool
Gere Sunder-Plassmann, MD
Role: PRINCIPAL_INVESTIGATOR
Medical University of Vienna
Giuseppe Toffoli, MD
Role: PRINCIPAL_INVESTIGATOR
Centro di Riferimento Oncologico
Cristina Lucía Dávila Fajardo, PharmD PhD
Role: PRINCIPAL_INVESTIGATOR
Andaluz Health Service
George P. Patrinos, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Patras
Vita Dolzan, MD PhD
Role: PRINCIPAL_INVESTIGATOR
University of Ljubljana
Locations
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Medical University of Vienna
Vienna, , Austria
University of Patras
Pátrai, , Greece
Centro di Riferimento Oncologico
Aviano, , Italy
Leiden University Medical Center
Leiden, , Netherlands
University of Ljubljana
Ljubljana, , Slovenia
Servicio Andaluz de Salud
Granada, , Spain
University of Liverpool
Liverpool, , United Kingdom
Countries
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References
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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.
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.
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.
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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Ubiquitous Pharmacogenomics (U-PGx) Consortium Official Website
Other Identifiers
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668353 (U-PGx)
Identifier Type: -
Identifier Source: org_study_id
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