PREemptive Pharmacogenomic Testing for Preventing Adverse Drug REactions (PREPARE)
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|ClinicalTrials.gov Identifier: NCT03093818|
Recruitment Status : Recruiting
First Posted : March 28, 2017
Last Update Posted : September 13, 2018
|Condition or disease||Intervention/treatment||Phase|
|Adverse Drug Reaction||Other: Pharmacogenomic testing||Not Applicable|
Pre-emptive pharmacogenomic testing will be implemented in clinical sites across seven European countries (United Kingdom, The Netherlands, Austria, Greece, Slovenia, Italy and Spain). The 35-month study is split into two time-blocks. The participating countries are randomized to start with either implementing pharmacogenomics guided prescribing or with standard of care in the first block. In the pharmacogenomics guided prescribing arm, results of the pharmacogenomic test will be incorporated in the (electronic) medical record and may be used by physicians and pharmacists to guide drug and dose selection for 39 routinely prescribed drugs, as per the Dutch Pharmacogenomics Working Group guidelines. In the standard of care arm, patients will not receive pharmacogenomic testing. After this time-block, the countries switch to implementing the opposite strategy and will recruit new patients.
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 19 months. In total, 6,892 patients will be recruited; 3,446 will receive pharmacogenomic testing, and 3,446 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%).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||6892 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Single (Outcomes Assessor)|
A random 10% sample of causality and severity of recorded ADE will be assessed by a 2nd 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.
|Official Title:||PREemptive Pharmacogenomic Testing for Preventing Adverse Drug REactions|
|Actual Study Start Date :||March 20, 2017|
|Estimated Primary Completion Date :||May 2020|
|Estimated Study Completion Date :||May 2020|
Experimental: Pharmacogenomic testing arm
3,446 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
The pharmacogenomic panel to be used incorporates 44 genetic variants for the following 12 "pharamacogenes": CYP1A2 (cytochrome P450), CYP2B6, CYP2C19, CYP2C9, CYP2D6,CYP3A4, DPYD (dihydropyrimidine dehydrogenase), FVL (factor five Leiden), HLA-B (human leukocyte antigen), SLCO1B1 (solute carrier organic anion transporter), TPMT (thiopurine methyltransferase), UGT1A1 (UDP-glucuronosyltransferase), and VKORC1 (vitamin K epoxide reductase complex).
No Intervention: Standard of care arm
3,446 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.
- Experience of at least one clinically relevant adverse drug reaction which is caused by the drug of inclusion [ Time Frame: 12 weeks ]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). For oncology patients receiving 5-FU, capecitabine, tegafur or irinotecan, only hematological toxicities of NCI-CTCAE grade 4-5 and non-hematological toxicities of NCI-CTCAE grade 3-5 will be considered clinically relevant.
- Physician and pharmacist adherence to Dutch Pharmacogenomics Working Group guidelines [ Time Frame: 18 months ]Defined as adhering to the guidelines or not adhering to the guidelines
- Healthcare expenditure related to adverse events [ Time Frame: 18 months ]Any costs made as a result of an adverse event
- Incidence of drug discontinuation due to an adverse event [ Time Frame: 18 months ]Related to the drug of inclusion
- Incidence of discontinuation due to lack of efficacy [ Time Frame: 18 months ]Related to the drug of inclusion
- Quality of life [ Time Frame: 18 months ]Time trade-off question
- Incidence of dose adjustments [ Time Frame: 18 months ]Related to the drug of inclusion
- Attitudes towards and knowledge of pharmacogenomics [ Time Frame: 18 months ]Composite outcome: a list of seven questions regarding pharmacogenomics
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03093818
|Contact: Cathelijne H van der Wouden, PharmD||+31 (0)70 email@example.com|
|Medical University of Vienna||Recruiting|
|Contact: Gere Sunder-Plassmann, MD firstname.lastname@example.org|
|Principal Investigator: Gere Sunder-Plassmann, MD|
|University of Patras||Recruiting|
|Contact: George P. Patrinos, PhD email@example.com|
|Principal Investigator: George P. Patrinos, PhD|
|Centro di Riferimento Oncologico||Recruiting|
|Contact: Erika Cecchin, PharmD PhD firstname.lastname@example.org|
|Principal Investigator: Giuseppe Toffoli, MD|
|Leiden University Medical Center||Recruiting|
|Contact: Cathelijne van der Wouden, PharmD email@example.com|
|Principal Investigator: Jesse J. Swen, PharmD PhD|
|University of Ljubljana||Recruiting|
|Contact: Vita Dolzan, MD PhD firstname.lastname@example.org|
|Principal Investigator: Vita Dolzan, MD PhD|
|Servicio Andaluz de Salud||Recruiting|
|Contact: Cristina L. Dávila Fajardo, PharmD PhD email@example.com|
|Principal Investigator: Cristina L. Dávila Fajardo, PharmD PhD|
|University of Liverpool||Recruiting|
|Liverpool, United Kingdom|
|Contact: Richard Turner, MD Richard.Turner@liverpool.ac.uk|
|Principal Investigator: Munir Pirmohamed, MB ChB(Hons) PhD|
|Principal Investigator:||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|