Drug-Related Side Effects and Adverse ReactionsDARES1NCT04580589
DOAC ADRs Retrospective Study on Genetic Variations
An observational study of Drug-Related Side Effects and Adverse Reactions and Treatment Failure, run by Cipherome, Inc. at 1 site in United States.
Trial summary
The purpose of this study is to see if the participant's genetic profile and clinical factors (age, drug dose, etc.) affect drug outcomes (i.e. serious bleeding) that the participant may have experienced since taking the drug (direct oral anticoagulant) for preventing blood clots from forming in the blood vessels. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug-Related Side Effects and Adverse Reactions, Treatment Failure
- Type of treatment
- Pill or oral medicine
- How many people
- 210 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2021to 31 Oct 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Any adult patient 18 years and older, who experienced major bleeding, clinically relevant non major bleeding or treatment failure while taking a DOAC during the study time frame and is able to provide informed consent.
Who may be able to join
- Any adult patient 18 years and older, who experienced major bleeding, clinically relevant non major bleeding or treatment failure while taking a DOAC during the study time frame and is able to provide informed consent. Control patients will be recruited from all adult patients who are on DOAC therapy.
Who cannot join
- Failure to provide informed consent
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: Investigation of Genetic Variations on Patients With Adverse Events While on Direct Oral Anticoagulants (DOACs)
The purpose of this study is to see if the participant's genetic profile and clinical factors (age, drug dose, etc.) affect drug outcomes (i.e. serious bleeding) that the participant may have experienced since taking the drug (direct oral anticoagulant) for preventing blood clots from forming in the blood vessels.
Read the detailed description
Genes can have variants or mutations that can increase the participant's risk for bleeding when receiving a direct oral anticoagulant (DOACs). The investigators will be studying participants on DOACs who have had bleeding and also participants who are on DOACs who did not have bleeding (control group). The goal of the study is to determine the accuracy of Cipherome's Drug Safety Score (DSS) in it's ability to predict adverse drug reactions (ADRs). A DSS score ranges from 0 to 1, with scores less than 0.3 correlated with a higher risk of ADRs and scores more than 0.7 correlated with a lower risk of ADRs. The participant's DSS score will be compared with the actual clinical outcome using a statistical test to determine the accuracy of the DSS.
- Medical subject headings
- Drug-Related Side Effects and Adverse Reactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Adverse Drug Reaction on DOAC | Participants on Direct Oral Anti-coagulants (DOACs) who experience major bleeding or clinically relevant non-major bleeding per International Society of Thrombosis and Haemostasis criteria. This is an observational study, so there will be no intervention. | |
| Treatment Failure on DOAC | Participants on Direct Oral Anti-coagulants (DOACs) who experience treatment failure (e.g., recurrent MI, systemic embolism, ischemic stroke, etc.). This is an observational study, so there will be no intervention. | |
| Case Control | Participants on Direct Oral Anti-coagulants (DOACs) who experience neither major bleeding or treatment failure. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major bleeding event during DOAC therapy
- Reduction in hemoglobin of at least 2 g/dL
- Blood loss requiring transfusion of at least 2 units of whole blood or erythrocytes
- Critical anatomical sites of bleeding: intramuscular with compartment syndrome, intracranial, intraspinal, retroperitoneal, intraocular, pericardial, and atraumatic intra-articular bleeding.
- Bleeding leading to death
Measured: Within 1 year of DOAC therapy initiation
Clinically relevant non-major bleeding
- Hospital admission for bleeding, or
- Physician guided medical or surgical treatment for bleeding, or
- Change in antithrombotic therapy (including interruption or discontinuation of study drug).
Measured: Within 1 year of DOAC therapy initiation
Secondary outcomes (1)
Thromboembolic events
Thromboembolic events including, but not limited to: deep vein thrombosis, pulmonary embolism, ischemic stroke, transient ischemic attack, arterial thrombosis, or other thromboembolic event
Measured: Within 1 year of DOAC therapy initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2020
- Study start1 Feb 2021
- Primary completion31 Oct 2022
- Study completion31 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Drug-Related Side Effects and Adverse ReactionsStudies 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
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 210 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
- Dayani Nualles-Percy, MD, Principal investigator, Santa Clara Valley Medical CenterClifford Wang, MD, Study director, Santa Clara Valley Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04580589
- Sponsor's protocol ID
- C02-001 SC003
- Acronym
- DARES1
- Status last verified
- Feb 2023
- First submitted
- 2 Oct 2020
- Last updated
- 16 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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 22224125Kirley K, Qato DM, Kornfield R, Stafford RS, Alexander GC. National trends in oral anticoagulant use in the United States, 2007 to 2011. Circ Cardiovasc Qual Outcomes. 2012 Sep 1;5(5):615-21. doi: 10.1161/CIRCOUTCOMES.112.967299. Epub 2012 Sep 4.
PubMed 22949490Bauer KA. Pros and cons of new oral anticoagulants. Hematology Am Soc Hematol Educ Program. 2013;2013:464-70. doi: 10.1182/asheducation-2013.1.464.
PubMed 24319220Kanuri SH, Kreutz RP. Pharmacogenomics of Novel Direct Oral Anticoagulants: Newly Identified Genes and Genetic Variants. J Pers Med. 2019 Jan 17;9(1):7. doi: 10.3390/jpm9010007.
PubMed 30658513Sennesael AL, Larock AS, Douxfils J, Elens L, Stillemans G, Wiesen M, Taubert M, Dogne JM, Spinewine A, Mullier F. Rivaroxaban plasma levels in patients admitted for bleeding events: insights from a prospective study. Thromb J. 2018 Nov 12;16:28. doi: 10.1186/s12959-018-0183-3. eCollection 2018.
PubMed 30455596Ing Lorenzini K, Daali Y, Fontana P, Desmeules J, Samer C. Rivaroxaban-Induced Hemorrhage Associated with ABCB1 Genetic Defect. Front Pharmacol. 2016 Dec 19;7:494. doi: 10.3389/fphar.2016.00494. eCollection 2016.
PubMed 28066243Ueshima S, Hira D, Kimura Y, Fujii R, Tomitsuka C, Yamane T, Tabuchi Y, Ozawa T, Itoh H, Ohno S, Horie M, Terada T, Katsura T. Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult patients with atrial fibrillation. Br J Clin Pharmacol. 2018 Jun;84(6):1301-1312. doi: 10.1111/bcp.13561. Epub 2018 Apr 16.
PubMed 29457840Shi J, Wang X, Nguyen JH, Bleske BE, Liang Y, Liu L, Zhu HJ. Dabigatran etexilate activation is affected by the CES1 genetic polymorphism G143E (rs71647871) and gender. Biochem Pharmacol. 2016 Nov 1;119:76-84. doi: 10.1016/j.bcp.2016.09.003. Epub 2016 Sep 8.
PubMed 27614009Dimatteo C, D'Andrea G, Vecchione G, Paoletti O, Cappucci F, Tiscia GL, Buono M, Grandone E, Testa S, Margaglione M. Pharmacogenetics of dabigatran etexilate interindividual variability. Thromb Res. 2016 Aug;144:1-5. doi: 10.1016/j.thromres.2016.05.025. Epub 2016 May 26.
PubMed 27261537Sychev DA, Levanov AN, Shelekhova TV, Bochkov PO, Denisenko NP, Ryzhikova KA, Mirzaev KB, Grishina EA, Gavrilov MA, Ramenskaya GV, Kozlov AV, Bogoslovsky T. The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty. Pharmgenomics Pers Med. 2018 Jul 25;11:127-137. doi: 10.2147/PGPM.S169277. eCollection 2018.
PubMed 301007501000 Genomes Project Consortium; Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR. A global reference for human genetic variation. Nature. 2015 Oct 1;526(7571):68-74. doi: 10.1038/nature15393.
PubMed 26432245Beckman MG, Hooper WC, Critchley SE, Ortel TL. Venous thromboembolism: a public health concern. Am J Prev Med. 2010 Apr;38(4 Suppl):S495-501. doi: 10.1016/j.amepre.2009.12.017.
PubMed 20331949Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. doi: 10.1056/NEJMoa1113697.
PubMed 23425163
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Genetic Variations on Patients With Adverse Events While on Direct Oral Anticoagulants (DOACs)
- ClinicalTrials.gov ID
- NCT04580589
- Acronym / sponsor ID
- DARES1 / C02-001 SC003
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 210 participants (actual)
- Lead sponsor
- Cipherome, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Santa Clara Valley Medical Center
- Study start
- 1 Feb 2021 (actual)
- Primary completion
- 31 Oct 2022 (actual)
- Study completion
- 31 Oct 2022 (actual)
- First posted
- 8 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see if the participant's genetic profile and clinical factors (age, drug dose, etc.) affect drug outcomes (i.e. serious bleeding) that the participant may have experienced since taking the drug (direct oral anticoagulant) for preventing blood clots from forming in the blood vessels.
Detailed description
Genes can have variants or mutations that can increase the participant's risk for bleeding when receiving a direct oral anticoagulant (DOACs). The investigators will be studying participants on DOACs who have had bleeding and also participants who are on DOACs who did not have bleeding (control group). The goal of the study is to determine the accuracy of Cipherome's Drug Safety Score (DSS) in it's ability to predict adverse drug reactions (ADRs). A DSS score ranges from 0 to 1, with scores less than 0.3 correlated with a higher risk of ADRs and scores more than 0.7 correlated with a lower risk of ADRs. The participant's DSS score will be compared with the actual clinical outcome using a statistical test to determine the accuracy of the DSS.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Adverse Drug Reaction on DOAC | – | –Participants on Direct Oral Anti-coagulants (DOACs) who experience major bleeding or clinically relevant non-major bleeding per International Society of Thrombosis and Haemostasis criteria. This is an observational study, so there will be no intervention. |
| Treatment Failure on DOAC | – | –Participants on Direct Oral Anti-coagulants (DOACs) who experience treatment failure (e.g., recurrent MI, systemic embolism, ischemic stroke, etc.). This is an observational study, so there will be no intervention. |
| Case Control | – | –Participants on Direct Oral Anti-coagulants (DOACs) who experience neither major bleeding or treatment failure. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Any adult patient 18 years and older, who experienced major bleeding, clinically relevant non major bleeding or treatment failure while taking a DOAC during the study time frame and is able to provide informed consent.
Key inclusion criteria (1 listed)
- Any adult patient 18 years and older, who experienced major bleeding, clinically relevant non major bleeding or treatment failure while taking a DOAC during the study time frame and is able to provide informed consent. Control patients will be recruited from all adult patients who are on DOAC therapy.
Key exclusion criteria (1 listed)
- Failure to provide informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Major bleeding event during DOAC therapy
Time frame: Within 1 year of DOAC therapy initiation
* Reduction in hemoglobin of at least 2 g/dL * Blood loss requiring transfusion of at least 2 units of whole blood or erythrocytes * Critical anatomical sites of bleeding: intramuscular with compartment syndrome, intracranial, intraspinal, retroperitoneal, intraocular, pericardial, and atraumatic intra-articular bleeding. * Bleeding leading to death
Clinically relevant non-major bleeding
Time frame: Within 1 year of DOAC therapy initiation
* Hospital admission for bleeding, or * Physician guided medical or surgical treatment for bleeding, or * Change in antithrombotic therapy (including interruption or discontinuation of study drug).
1 secondary outcome
Thromboembolic events
Time frame: Within 1 year of DOAC therapy initiation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2023.
- Background: PubMed 23831166Colilla 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.
- Background: PubMed 17620536Wysowski 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.
- Background: PubMed 22224125Zareh 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.
- Background: PubMed 22949490Kirley K, Qato DM, Kornfield R, Stafford RS, Alexander GC. National trends in oral anticoagulant use in the United States, 2007 to 2011. Circ Cardiovasc Qual Outcomes. 2012 Sep 1;5(5):615-21. doi: 10.1161/CIRCOUTCOMES.112.967299. Epub 2012 Sep 4.
- Background: PubMed 24319220Bauer KA. Pros and cons of new oral anticoagulants. Hematology Am Soc Hematol Educ Program. 2013;2013:464-70. doi: 10.1182/asheducation-2013.1.464.
- Background: PubMed 30658513Kanuri SH, Kreutz RP. Pharmacogenomics of Novel Direct Oral Anticoagulants: Newly Identified Genes and Genetic Variants. J Pers Med. 2019 Jan 17;9(1):7. doi: 10.3390/jpm9010007.
- Background: PubMed 30455596Sennesael AL, Larock AS, Douxfils J, Elens L, Stillemans G, Wiesen M, Taubert M, Dogne JM, Spinewine A, Mullier F. Rivaroxaban plasma levels in patients admitted for bleeding events: insights from a prospective study. Thromb J. 2018 Nov 12;16:28. doi: 10.1186/s12959-018-0183-3. eCollection 2018.
- Background: PubMed 28066243Ing Lorenzini K, Daali Y, Fontana P, Desmeules J, Samer C. Rivaroxaban-Induced Hemorrhage Associated with ABCB1 Genetic Defect. Front Pharmacol. 2016 Dec 19;7:494. doi: 10.3389/fphar.2016.00494. eCollection 2016.
- Background: PubMed 29457840Ueshima S, Hira D, Kimura Y, Fujii R, Tomitsuka C, Yamane T, Tabuchi Y, Ozawa T, Itoh H, Ohno S, Horie M, Terada T, Katsura T. Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult patients with atrial fibrillation. Br J Clin Pharmacol. 2018 Jun;84(6):1301-1312. doi: 10.1111/bcp.13561. Epub 2018 Apr 16.
- Background: PubMed 27614009Shi J, Wang X, Nguyen JH, Bleske BE, Liang Y, Liu L, Zhu HJ. Dabigatran etexilate activation is affected by the CES1 genetic polymorphism G143E (rs71647871) and gender. Biochem Pharmacol. 2016 Nov 1;119:76-84. doi: 10.1016/j.bcp.2016.09.003. Epub 2016 Sep 8.
- Background: PubMed 27261537Dimatteo C, D'Andrea G, Vecchione G, Paoletti O, Cappucci F, Tiscia GL, Buono M, Grandone E, Testa S, Margaglione M. Pharmacogenetics of dabigatran etexilate interindividual variability. Thromb Res. 2016 Aug;144:1-5. doi: 10.1016/j.thromres.2016.05.025. Epub 2016 May 26.
- Background: PubMed 30100750Sychev DA, Levanov AN, Shelekhova TV, Bochkov PO, Denisenko NP, Ryzhikova KA, Mirzaev KB, Grishina EA, Gavrilov MA, Ramenskaya GV, Kozlov AV, Bogoslovsky T. The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty. Pharmgenomics Pers Med. 2018 Jul 25;11:127-137. doi: 10.2147/PGPM.S169277. eCollection 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dayani Nualles-Percy, MD principal investigator
Santa Clara Valley Medical Center
Clifford Wang, MD study director
Santa Clara Valley Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Drug-Related Side Effects and Adverse Reactions and Treatment Failure, 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 1 inclusion and 1 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?
Major bleeding event during DOAC therapy (time frame: Within 1 year of DOAC therapy initiation). The study lists 2 primary outcomes in all. 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 NCT04580589, which also lists 15 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.