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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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
How many people
200 participants
Where
1 siteUnited States
Study dates
11 Feb 2019to 30 Sep 2022
Phase
Observational
Are there results?
None posted in the registry

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

Other trials in United States

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.

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.

  1. 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)

  1. 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

  2. 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

  3. Ischemic stroke

    Development of a clinical diagnosis of an ischemic stroke

    Measured: 12 weeks

  4. 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

  5. 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.

  1. First posted29 Mar 2019
  2. Study start11 Feb 2019
  3. Primary completion30 Sep 2022
  4. Study completion30 Sep 2022

Resources

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)
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 23831166

  • Wysowski 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 17620536

  • Zareh 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 22224125

  • Johnson 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 28198005

  • Cavallari 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 22871196

  • https://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 24251363

  • Kimmel 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 24251361

  • Rosendaal 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 8470047

  • Schulman 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 15842354

  • Lip 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 9015466

  • Cregler 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

Questions about this trial

What is this clinical trial studying?

An observational study of Atrial Fibrillation and Deep Vein Thrombosis, run by Cipherome, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent time in therapeutic range during initial 12 weeks of warfarin (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03894878, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2023; AzTrials last refreshed its copy on 6 Nov 2026.

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