Association Between Genetic Variant Scores and DOACs (DARES2)

Study Overview
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Brief Summary
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The study's objective is to evaluate the predictive accuracy of Cipherome's algorithm in predicting and preventing serious adverse drug reactions (ADRs) experienced by patients while on direct oral anti-coagulants (DOACs).

Official Title
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Correlation Between Bleeding Complication and Treatment Failure of DOAC and Its Predictions Based on Cipherome's Pharmacogenomic Technology

Conditions
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Drug-Related Side Effects and Adverse Reactions, Iatrogenic Disorder

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any adult patient 18 years and older, who experienced a serious adverse drug reaction while taking a DOAC and is able to provide informed consent. Exclusion Criteria: Failure to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ADR Group<br>ISTH bleeding scale Major Bleeding | |
| Control Group<br>No ADR, No Treatment Failure | |
| Treatment Failure Group<br>Recurrent MI, Ischemic stroke, Other thromboembolic disorders | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the predictive accuracy of Cipherome's Drug Safety Score (DSS) in correlating with serious Adverse Drug Reactions associated with Direct Oral Anti-coagulants (DOACs) (rivaroxaban, apixaban, dabigatran, and edoxaban). | The primary endpoint is to determine the accuracy of the DSS in predicting clinical outcomes of major bleeding per International Society of Thrombosis and Haemostatis (ISTH) criteria in subjects on Direct Oral Anti-coagulants (DOACs). The DSS is calculated on a scale of 0 to 1, with scores below 0.3 correlated with a higher risk of ADRs and scores above 0.7 correlated with a lower risk of ADRs. We will determine the DSS of all subjects who experienced major bleeding and compare it to the DSS of control subjects who did not experience bleeding. | Within 1 year of DOAC therapy initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the predictive accuracy of the DSS in correlating with serious ADRs compared to clinical tools (e.g., HAS BLED criteria). | The secondary endpoint is to determine the accuracy of the DSS predicting clinical outcomes compared to clinical tools such as the HAS-BLED scoring system. A subject with a HAS-BLED score of > 4 points will be considered moderate-high risk of bleeding and a HAS-BLED score of 4 or less will be considered low risk. A DSS is calculated on a scale of 0 to 1, with scores below 0.3 correlated with a higher risk of ADRs and scores above 0.7 correlated with a lower risk of ADRs. Both DSS (low and high risk subjects) and HAS-BLED scores (low and high risk subjects) will be compared to actual clinical outcomes to assess the predictive accuracy of each scoring system. | Within 1 year of DOAC therapy initiation | 
| To evaluate the predictive accuracy of the DSS in correlating with treatment failures while on Direct Oral Anti-coagulants (DOACs) | The secondary endpoint is to determine the accuracy of the DSS in predicting treatment failures (e.g., recurrent MI, systemic embolism, or ischemic stroke) as compared to clinical outcomes while on DOACs. The DSS is calculated on a scale of 0 to 1, with preliminary studies demonstrating that scores below 0.3 correlated with a higher risk of ADRs and scores above 0.7 correlated with a lower risk of ADRs. | Within 1 year of DOAC therapy initiation |