DOAC ADRs Retrospective Study on Genetic Variations

Study Overview
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Brief Summary
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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
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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.

Official Title
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Investigation of Genetic Variations on Patients With Adverse Events While on Direct Oral Anticoagulants (DOACs)

Conditions
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Drug-Related Side Effects and Adverse Reactions, Treatment Failure

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: Failure to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adverse Drug Reaction on DOAC<br>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<br>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<br>Participants on Direct Oral Anti-coagulants (DOACs) who experience neither major bleeding or treatment failure. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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). | Within 1 year of DOAC therapy initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Within 1 year of DOAC therapy initiation |