Ignite Creation Date:
2025-12-24 @ 5:14 PM
Ignite Modification Date:
2025-12-29 @ 8:30 AM
Study NCT ID:
NCT00521950
Status:
COMPLETED
Last Update Posted:
2014-03-28
First Post:
2007-08-27
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Cost-effectiveness of TPMT Pharmacogenetics
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015212', 'term': 'Inflammatory Bowel Diseases'}, {'id': 'D003424', 'term': 'Crohn Disease'}, {'id': 'D003093', 'term': 'Colitis, Ulcerative'}], 'ancestors': [{'id': 'D005759', 'term': 'Gastroenteritis'}, {'id': 'D005767', 'term': 'Gastrointestinal Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D007410', 'term': 'Intestinal Diseases'}, {'id': 'D003092', 'term': 'Colitis'}, {'id': 'D003108', 'term': 'Colonic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D001379', 'term': 'Azathioprine'}, {'id': 'D015122', 'term': 'Mercaptopurine'}], 'ancestors': [{'id': 'D013872', 'term': 'Thionucleosides'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011687', 'term': 'Purines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}, {'id': 'D013438', 'term': 'Sulfhydryl Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'SUPPORTIVE_CARE', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 853}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2007-09'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2014-03', 'completionDateStruct': {'date': '2011-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2014-03-27', 'studyFirstSubmitDate': '2007-08-27', 'studyFirstSubmitQcDate': '2007-08-27', 'lastUpdatePostDateStruct': {'date': '2014-03-28', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2007-08-28', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2011-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Haematological adverse drug reactions', 'timeFrame': '0-5 months'}], 'secondaryOutcomes': [{'measure': 'Non-haematological Adverse Drug Reactions', 'timeFrame': '0- 5 months'}, {'measure': 'Clinical outcome (disease activity)', 'timeFrame': '5 months'}, {'measure': 'Treatment compliance', 'timeFrame': '0 to 5 months'}, {'measure': 'TPMT enzym activity', 'timeFrame': 'at baseline'}, {'measure': 'Therapeutic Drug Monitoring of TPMT Metabolites', 'timeFrame': 'week 1 and 8'}, {'measure': 'Health related quality of life', 'timeFrame': '5 months'}, {'measure': 'Cost-efficacy', 'timeFrame': '5 months'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Pharmacogenetics', 'Cost Effectiveness', 'Inflammatory Bowel Diseases', 'Crohn Disease', 'Ulcerative Colitis', 'Randomized Controlled Trials'], 'conditions': ['Inflammatory Bowel Diseases', 'Crohn Disease', 'Ulcerative Colitis']}, 'referencesModule': {'references': [{'pmid': '27943397', 'type': 'DERIVED', 'citation': 'Wong DR, Coenen MJ, Derijks LJ, Vermeulen SH, van Marrewijk CJ, Klungel OH, Scheffer H, Franke B, Guchelaar HJ, de Jong DJ, Engels LG, Verbeek AL, Hooymans PM; TOPIC Recruitment Team. Early prediction of thiopurine-induced hepatotoxicity in inflammatory bowel disease. Aliment Pharmacol Ther. 2017 Feb;45(3):391-402. doi: 10.1111/apt.13879. Epub 2016 Dec 12.'}, {'pmid': '27402913', 'type': 'DERIVED', 'citation': 'Wong DR, Coenen MJ, Vermeulen SH, Derijks LJ, van Marrewijk CJ, Klungel OH, Scheffer H, Franke B, Guchelaar HJ, de Jong DJ, Engels LG, Verbeek AL, Hooymans PM; TOPIC recruitment team. Early Assessment of Thiopurine Metabolites Identifies Patients at Risk of Thiopurine-induced Leukopenia in Inflammatory Bowel Disease. J Crohns Colitis. 2017 Feb;11(2):175-184. doi: 10.1093/ecco-jcc/jjw130. Epub 2016 Jul 9.'}, {'pmid': '26072396', 'type': 'DERIVED', 'citation': 'Coenen MJ, de Jong DJ, van Marrewijk CJ, Derijks LJ, Vermeulen SH, Wong DR, Klungel OH, Verbeek AL, Hooymans PM, Peters WH, te Morsche RH, Newman WG, Scheffer H, Guchelaar HJ, Franke B; TOPIC Recruitment Team. Identification of Patients With Variants in TPMT and Dose Reduction Reduces Hematologic Events During Thiopurine Treatment of Inflammatory Bowel Disease. Gastroenterology. 2015 Oct;149(4):907-17.e7. doi: 10.1053/j.gastro.2015.06.002. Epub 2015 Jun 11.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to determine whether thiopurine S-methyltransferase (TPMT) genotyping prior to thiopurine use is cost-effective in patients with inflammatory bowel disease (IBD) in need of immune suppression.\n\nThe study is designed to test the hypothesis that optimization of initial thiopurine dose based on pre-treatment TPMT genotyping will maximize treatment efficacy and minimize adverse drug reactions (ADRs) resulting in reduced costs.', 'detailedDescription': "Immunosuppressives, e.g. azathioprine (AZA) and 6-mercaptopurine (6-MP), are important in induction of remission and long term treatment of (ulcerative) colitis and Crohn's disease when treatment with 5-aminosalicylates and corticosteroids fails. ADRs to immunosuppressive treatment, including myelosuppression and hepatotoxicity, are frequently (15-30%) observed. Genetic variation in the TPMT gene results in 10-11% of the general population in reduced and in 0.3-0.6% to negligible TPMT enzyme activity. In IBD patients, this genetic variation predicts 25-40% of the haematological ADRs necessitating tempering of thiopurine dose or discontinuation of treatment.\n\nPharmacogenetics aims at providing optimized drug treatment to patients by maximizing efficacy and minimizing adverse drug reactions (ADRs) based on genetic testing. Despite the proven value of pharmacogenetics in clinical practice, its use in medical care is still limited.\n\nThe best-established example of a pharmacogenetic test is genotyping of thiopurine S-methyltransferase (TPMT) in the treatment of patients with immunosuppressive thiopurines. Nonetheless, it is not used on a large scale in clinical practice so far, which might be due to: insufficient information transfer from research to clinic; lack of cost-effectiveness analyses (CEAs); lack of availability of (or access to) fast and/or cheap genotyping; or lack of test reimbursement by health insurance."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age 18 or older\n* Diagnosis of a form of IBD\n* Indication for azathioprine/6-MP treatment\n* Patient giving (written) informed consent\n\nExclusion Criteria:\n\n* Previous treatment with azathioprine/6-MP\n* Co-prescription of allopurinol (this treatment blocks xanthine oxidase, an enzyme important for thiopurine metabolism)\n* Baseline leukocyte count less then 3x10\\^9 per litre\n* Reduced liver function at baseline\n* Reduced renal function at baseline\n* Known TPMT phenotype (enzyme activity / Therapeutic Drug Monitoring) or genotype\n* Pregnancy or breastfeeding'}, 'identificationModule': {'nctId': 'NCT00521950', 'acronym': 'TOPIC', 'briefTitle': 'Cost-effectiveness of TPMT Pharmacogenetics', 'organization': {'class': 'OTHER', 'fullName': 'Radboud University Medical Center'}, 'officialTitle': 'Pharmacogenetic Testing in the Clinical Setting: is Screening for TPMT Genotype a Cost-effective Treatment Strategy? - The First Prospective Randomized Controlled Trial Within the Dutch Health Care System.', 'orgStudyIdInfo': {'id': '945-07-606'}, 'secondaryIdInfos': [{'id': 'CMO 2006/129'}, {'id': 'ABR NL13171.091.06'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Intervention, TPMT genotyping', 'description': 'Pre-treatment TPMT genotyping to optimize initial thiopurine treatment dose. Intervention is based on the genotype.', 'interventionNames': ['Genetic: TPMT genotyping; Drug: azathioprine or 6-mercaptopurine']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'control', 'description': 'Standard thiopurine treatment', 'interventionNames': ['Drug: azathioprine (AZA) or 6-mercaptopurine (6-MP)']}], 'interventions': [{'name': 'TPMT genotyping; Drug: azathioprine or 6-mercaptopurine', 'type': 'GENETIC', 'otherNames': ['Imuran', 'Puri-Nethol'], 'description': 'Assessment of the polymorphisms G238C, G460A, and A719G in a venous blood sample to identify functional genetic variants (TPMT\\*2, \\*3A, \\*3C) of the TPMT gene (chromosome 6) associated with reduced or negligible TPMT enzyme activity.\n\nPatients are advised an initial treatment dose based on the enzyme activity:\n\n* Normal: AZA 2-2.5 mg/kg/day or 6-MP 1-1.5 mg/kg/day (standard care);\n* Reduced: AZA 1-1.25 mg/kg/day or 6-MP 0.5-0.75 mg/kg/day;\n* Negligible: AZA 0-0.2 mg/kg/day or 6-MP 0-0.1 mg/kg/day;', 'armGroupLabels': ['Intervention, TPMT genotyping']}, {'name': 'azathioprine (AZA) or 6-mercaptopurine (6-MP)', 'type': 'DRUG', 'otherNames': ['Imuran', 'Puri-Nethol'], 'description': 'Patients will be advised a standard initial treatment dose:\n\n* AZA 2-2.5 mg/kg/day or 6-MP 1-1.5 mg/kg/day (standard care);', 'armGroupLabels': ['control']}]}, 'contactsLocationsModule': {'locations': [{'zip': '6500 HB', 'city': 'Nijmegen', 'state': 'Gelderland', 'country': 'Netherlands', 'facility': 'Radboud University Medical Center', 'geoPoint': {'lat': 51.8425, 'lon': 5.85278}}, {'zip': '5342 BT', 'city': 'Oss', 'country': 'Netherlands', 'facility': 'Bernhoven Hospital', 'geoPoint': {'lat': 51.765, 'lon': 5.51806}}, {'zip': '5461 AA', 'city': 'Veghel', 'country': 'Netherlands', 'facility': 'Bernhoven Hospital', 'geoPoint': {'lat': 51.61667, 'lon': 5.54861}}], 'overallOfficials': [{'name': 'Barbara Franke, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Radboud University Medical Center'}, {'name': 'Hans Scheffer, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'Radboud University Medical Center'}, {'name': 'Corine J van Marrewijk, MSc', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Radboud University Medical Center'}, {'name': 'Dirk J de Jong, MD PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Radboud University Medical Center'}, {'name': 'Marieke JH Coenen, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'Radboud University Medical Center'}, {'name': 'Henk-Jan Guchelaar, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'Leiden UMC'}, {'name': 'Luc Derijks, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'Maxima MC Veldhoven'}, {'name': 'Olaf Klungel, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'UMC Utrecht'}, {'name': 'André Verbeek, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'Radboud University Medical Center'}, {'name': 'Sita Vermeulen, MSc', 'role': 'STUDY_CHAIR', 'affiliation': 'Radboud University Medical Center'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'ZonMw: The Netherlands Organisation for Health Research and Development', 'class': 'OTHER'}, 'collaborators': [{'name': 'Radboud University Medical Center', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'PhD', 'investigatorFullName': 'Marieke Coenen', 'investigatorAffiliation': 'Radboud University Medical Center'}}}}