Ignite Creation Date:
2025-12-25 @ 1:33 AM
Ignite Modification Date:
2025-12-27 @ 11:43 PM
Study NCT ID:
NCT01964794
Status:
COMPLETED
Last Update Posted:
2016-10-07
First Post:
2013-10-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Improving Anticoagulant Therapy Through Warfarin Metabolite Profiling
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Blood specimens to identify coumadin genetic and metabolic biomarkers.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'CROSS_SECTIONAL', 'observationalModel': 'CASE_ONLY'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 60}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2012-05'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-10', 'completionDateStruct': {'date': '2016-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-10-06', 'studyFirstSubmitDate': '2013-10-09', 'studyFirstSubmitQcDate': '2013-10-14', 'lastUpdatePostDateStruct': {'date': '2016-10-07', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2013-10-17', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2016-10', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Metabolite Profiling', 'timeFrame': 'Up to 24 months', 'description': 'Based on a single blood draw, identify metabolite biomarkers for achieving a stable target anticoagulant response among patients at a maintenance dose of warfarin.'}]}, 'conditionsModule': {'keywords': ['Warfarin'], 'conditions': ['Stable Target INR']}, 'descriptionModule': {'briefSummary': 'Clinically relevant biomarkers for warfarin identified in this study will provide crucial leads for subsequent studies to assess their predictive value during anticoagulant therapy. This knowledge will aid stratifying risk among patients to improve therapeutic outcomes and decrease adverse drug events and associated health care costs. Collectively, these efforts will provide a critical foundation for future research using a metabolite biomarker strategy in a clinical setting to revolutionize warfarin therapy. Through its application, a real-time assessment of warfarin metabolism for each patient could lead to a truly personalized dosing strategy and improve patient safety for this life-saving drug.', 'detailedDescription': 'Coumadin (R/S-warfarin) is a commonly prescribed anticoagulant for over 20 million Americans for the treatment of atrial fibrillation, mechanical heart valves, venous thromboembolism and other coagulopathies. While highly efficacious, warfarin treatment is challenging due to a narrow therapeutic range and high inter-individual variations in response. Optimal warfarin dosage relies on a potentially lengthy trial-and-error process to optimize dosage for a desired anticoagulant response as measured by the international normalization ratio (INR), a prothrombin test. Even when a maintenance dose is achieved, patients are prone to testing out of the target INR range, and thus are at risk of hemorrhaging (over-dosing) or thromboembolism (under-dosing). In fact, warfarin is among the top ten drug-related causes of serious adverse drug events and increased health care costs. The progressive increase in warfarin use necessitates a better understanding of the mechanisms underlying inter-individual variability in responses to anticoagulant therapy. Our long-term goal is to identify metabolic biomarkers correlating with clinical responses to warfarin therapy and then utilize this knowledge to predict safe and effective dosing for patients based on a single blood draw.\n\nTherapeutic outcomes for patients involve a balance between warfarin dosing and its metabolism to maintain a stable target INR. There is an initial lengthy titration stage in which dosing is increased to achieve but not surpass a target INR range. The potency of this effect depends on warfarin metabolism, which counters the dosing effect on patients by inactivating the drug. Warfarin undergoes extensive metabolism through distinct enantio- and regio-specific metabolic pathways to yield a complex array of essentially inactive isomeric metabolites. Warfarin is clinically available as an equal mixture of R and S enantiomers. S-Warfarin is about four times more potent than R-warfarin, and presumably dominates the anticoagulant response to therapy. During maintenance dosing, a longer metabolic half-life for R-warfarin leads to higher accumulation levels in plasma than those observed for S-warfarin. Variations in R-and S-warfarin plasma levels may potentiate the anticoagulant effect of both drug isomers and the corresponding responses to therapy. For our exploratory study, we will identify biomarkers within patient metabolic profiles for R-and S-warfarin that predict clinical outcomes for the patients.'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '69 Years', 'minimumAge': '60 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Originally, for this pilot study, we chose a sample population size of 150 with a focus on veterans from the Korean War. Towards the end of recruitment the protocol was revised to remove the focus on veterans from just the Korean War.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Males aged 60 - 69 originally. Opened inclusion criteria age to include 18-79 years of age.\n2. Potential participant received a warfarin maintenance dose with a stable INR (defined as within target range over a two month (60 day) period that includes a minimum of two clinical visits).\n3. Potential participant has taken warfarin as prescribed over the past three days.\n\nExclusion Criteria:\n\n1. Female\n2. Potential participant receiving a warfarin while not achieving a stable INR (defined as within target range over a two month (60 day) period that includes a minimum of two clinical visits).\n3. Potential participant has not received any warfarin over the past three days.'}, 'identificationModule': {'nctId': 'NCT01964794', 'briefTitle': 'Improving Anticoagulant Therapy Through Warfarin Metabolite Profiling', 'organization': {'class': 'OTHER', 'fullName': 'University of Arkansas'}, 'officialTitle': 'Improving Anticoagulant Therapy Through Warfarin Metabolite Profiling', 'orgStudyIdInfo': {'id': '135288'}}, 'contactsLocationsModule': {'locations': [{'zip': '72205', 'city': 'Little Rock', 'state': 'Arkansas', 'country': 'United States', 'facility': 'Central Arkansas Veterans Healthcare System', 'geoPoint': {'lat': 34.74648, 'lon': -92.28959}}, {'zip': '72205', 'city': 'Little Rock', 'state': 'Arkansas', 'country': 'United States', 'facility': 'University of Arkansas for Medical Sciences', 'geoPoint': {'lat': 34.74648, 'lon': -92.28959}}], 'overallOfficials': [{'name': 'Grover P Miller, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Arkansas'}, {'name': 'Eugene Smith, III, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Dentral Arkansas Veterans Healthcare System'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Arkansas', 'class': 'OTHER'}, 'collaborators': [{'name': 'Central Arkansas Veterans Healthcare System', 'class': 'FED'}], 'responsibleParty': {'type': 'SPONSOR'}}}}