Atrial FibrillationAWARE1NCT03894878
Association Between Genetic Variant Scores and Warfarin Effect
An observational study of Atrial Fibrillation and Deep Vein Thrombosis, run by Cipherome, Inc. at 1 site in United States.
Trial summary
Study objective is to determine whether there is an association between genetic variant risk scores and clinical outcomes (percent time in therapeutic range, time to reach therapeutic international normalized ratio (INR), INR ≥ 4, bleeding event, ischemic stroke, death) in participants taking warfarin for atrial… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Atrial Fibrillation, Deep Vein Thrombosis, Intracardiac Thrombus
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Feb 2019to 30 Sep 2022
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 1. Participants with a known disease that predisposes them to bleeding will be excluded, since it will be a confounder (trying to link abnormal genetic variant risk score to bleeding). 2. Participants taking medications or on a diet that increases bleeding propensity will also be excluded. 3. Pediatric participants will be excluded from this study, since atrial fibrillation and/or venous thromboembolism are rare in this cohort.
Who may be able to join
- Non-valvular atrial fibrillation
- Deep venous thrombosis (DVT) and/or pulmonary embolism (PE) with no hypercoagulable condition
- Non-valvular atrial fibrillation and DVT/PE (with no hypercoagulable condition)
- Intracardiac thrombosis (i.e. apical thrombosis, atrial thrombosis, auricular thrombosis, mural thrombosis, and/or ventricular thrombosis)
- Age 18-99 years
- Signed informed consent
Who cannot join
- Presence of a mechanical heart valve
- Failure to provide signed informed consent
- Known diseases that affects coagulation test results such as vitamin K deficiency, disseminated intravascular coagulopathy, Von Willebrand disease, hemophilia, liver failure, etc.
Trial locations and contacts
1 site in 1 country.
United States1 site
Santa Clara Valley Medical Center
Santa Clara, California, 95128
About this study
Official title: Association Between Risk Scores for Genetic Variants and Percentage of Time in Therapeutic Range for Participants With Atrial Fibrillation, Deep Vein Thrombosis, and/or Intracardiac Thrombosis Taking Warfarin
Study objective is to determine whether there is an association between genetic variant risk scores and clinical outcomes (percent time in therapeutic range, time to reach therapeutic international normalized ratio (INR), INR ≥ 4, bleeding event, ischemic stroke, death) in participants taking warfarin for atrial fibrillation, deep vein thrombosis (DVT), pulmonary embolism (PE), and/or intracardiac thrombosis.
Read the detailed description
It is anticipated that next generation genomic sequencing will identify rare genetic variants in ethnically diverse populations, which otherwise would not have been detected using commercially available warfarin tests. Furthermore, retrospective review of clinical outcomes (percent time in therapeutic range, time to reach therapeutic international normalized ratio (INR), INR ≥ 4, major bleeding event, ischemic stroke) of study participants will determine the clinical utility of genetic variant risk scores. Study outcomes will provide guidance on future directions for optimizing dosing algorithms for warfarin that combine pharmacogenetic principles with clinical dosing.
- Conditions
- Atrial Fibrillation, Deep Vein Thrombosis, Intracardiac Thrombus, Pulmonary Embolism, Venous Thromboembolic Disease
- Keywords
- Warfarin, Coumadin, Pharmacogenomics, Pharmacogenetics, Adverse Drug Reactions, Bleeding/hemorrhaging
- Medical subject headings
- Atrial Fibrillation, Venous Thrombosis, Pulmonary Embolism, Drug-Related Side Effects and Adverse Reactions, Hemorrhage
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent time in therapeutic range during initial 12 weeks of warfarin
Within the 12 weeks of treatment, this is the percentage of time that a given participant is within the therapeutic range (e.g. participant is in therapeutic range 75% of time/12 weeks of measurement)
Measured: 12 weeks
Secondary outcomes (5)
Time to reach therapeutic INR
Time needed to achieve first INR within the range of 2 to 3, provided that subsequent INR ≥ 7 days later was also within the range of 2 to 3
Measured: 12 weeks
INR ≥ 4.0 during first 12 weeks of warfarin therapy
Time greater than the desired INR therapeutic range within the first 12 weeks of warfarin therapy
Measured: 12 weeks
Ischemic stroke
Development of a clinical diagnosis of an ischemic stroke
Measured: 12 weeks
Major bleeding event during first 12 weeks of warfarin therapy
Development of a major bleeding event during the first 12 weeks of warfarin therapy, diagnosed by a clinician
Measured: 12 weeks
Clinically relevant non-major bleeding event during the first 12 weeks of warfarin therapy
Development of a clinically relevant non-major bleeding event during the first 12 weeks of warfarin therapy, diagnosed by a clinician
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2019
- Study start11 Feb 2019
- Primary completion30 Sep 2022
- Study completion30 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cipherome, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Santa Clara Valley Medical Center
- Responsible party
- Sponsor
- Investigators
- Clifford Wang, MD, Principal investigator, Santa Clara Valley Medical CenterDayani Nualles-Percy, MD, Study director, Santa Clara Valley Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03894878
- Sponsor's protocol ID
- C01-001 SC001
- Acronym
- AWARE1
- Status last verified
- Feb 2023
- First submitted
- 27 Mar 2019
- Last updated
- 16 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Colilla S, Crow A, Petkun W, Singer DE, Simon T, Liu X. Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population. Am J Cardiol. 2013 Oct 15;112(8):1142-7. doi: 10.1016/j.amjcard.2013.05.063. Epub 2013 Jul 4.
PubMed 23831166Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use: a prevalent adverse effect resulting in regulatory action. Arch Intern Med. 2007 Jul 9;167(13):1414-9. doi: 10.1001/archinte.167.13.1414.
PubMed 17620536Zareh M, Davis A, Henderson S. Reversal of warfarin-induced hemorrhage in the emergency department. West J Emerg Med. 2011 Nov;12(4):386-92. doi: 10.5811/westjem.2011.3.2051.
PubMed 22224125Johnson JA, Caudle KE, Gong L, Whirl-Carrillo M, Stein CM, Scott SA, Lee MT, Gage BF, Kimmel SE, Perera MA, Anderson JL, Pirmohamed M, Klein TE, Limdi NA, Cavallari LH, Wadelius M. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update. Clin Pharmacol Ther. 2017 Sep;102(3):397-404. doi: 10.1002/cpt.668. Epub 2017 Apr 4.
PubMed 28198005Cavallari LH, Perera MA. The future of warfarin pharmacogenetics in under-represented minority groups. Future Cardiol. 2012 Jul;8(4):563-76. doi: 10.2217/fca.12.31.
PubMed 22871196https://www.bcbsks.com/CustomerService/Providers/MedicalPolicies/policies/policies/GeneticTesting_WarfarinDose_2017-09-01.pdf (Accessed July 22, 2019)
Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, Kesteven P, Christersson C, Wahlstrom B, Stafberg C, Zhang JE, Leathart JB, Kohnke H, Maitland-van der Zee AH, Williamson PR, Daly AK, Avery P, Kamali F, Wadelius M; EU-PACT Group. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013 Dec 12;369(24):2294-303. doi: 10.1056/NEJMoa1311386. Epub 2013 Nov 19.
PubMed 24251363Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, Rosenberg YD, Eby CS, Madigan RA, McBane RB, Abdel-Rahman SZ, Stevens SM, Yale S, Mohler ER 3rd, Fang MC, Shah V, Horenstein RB, Limdi NA, Muldowney JA 3rd, Gujral J, Delafontaine P, Desnick RJ, Ortel TL, Billett HH, Pendleton RC, Geller NL, Halperin JL, Goldhaber SZ, Caldwell MD, Califf RM, Ellenberg JH; COAG Investigators. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013 Dec 12;369(24):2283-93. doi: 10.1056/NEJMoa1310669. Epub 2013 Nov 19.
PubMed 24251361Rosendaal FR, Cannegieter SC, van der Meer FJ, Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993 Mar 1;69(3):236-9.
PubMed 8470047Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.
PubMed 15842354Lip GY. Intracardiac thrombus formation in cardiac impairment: the role of anticoagulant therapy. Postgrad Med J. 1996 Dec;72(854):731-8. doi: 10.1136/pgmj.72.854.731.
PubMed 9015466Cregler LL. Antithrombotic therapy in left ventricular thrombosis and systemic embolism. Am Heart J. 1992 Apr;123(4 Pt 2):1110-4. doi: 10.1016/0002-8703(92)91069-d.
PubMed 1553880