A Study to Describe the Characteristics, Health Care Interventions and Outcomes of Patients With Major Bleedings in the Presence of Factor Xa Inhibitor Treatment

Study Overview
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Brief Summary
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REVERXaL study aims to increase the understanding of the patient characteristics, bleeding presentation, health care interventions provided, and the clinical as well as self-reported health outcomes of patients with major bleeding in the presence of Factor Xa inhibitor treatment. The generation of insight on treatment approaches and associated outcomes in hospitalized patients with Factor Xa inhibitor-related major bleeds may inform clinical guidelines, health system decision making and streamline treatment pathways in this population.

Detailed Description
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REVERXaL is a multinational observational study incorporating 2 patient cohorts (historical and prospective) with major bleeds during Factor Xa inhibitor use. This study will be mainly descriptive in nature without any pre-specified statistical hypotheses. Variables will be collected according to routine medical practice either through primary data collection directly from patients, or from secondary data collection via data extraction from electronic or paper medical records into electronic case report forms (eCRFs). Patients will undergo clinical assessments and receive standard medical care as determined by their treating physicians. Patients will not receive any experimental disease management intervention or experimental treatment because of their participation in the study. As part of routine care, study investigators will evaluate patients about their medical history, medication history, bleeding presentation, and any adverse event (AE) or severe adverse event (SAE) experiences since the previous clinical visit and the related information. No additional or pre-defined site visits will be scheduled outside of the patient's routine clinical visits.

Official Title
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A Multinational Observational Longitudinal Study to Describe the Patient Characteristics, Health Care Interventions, and Health Outcomes of Patients With Major Bleedings in the Presence of Factor Xa Inhibitor Treatment

Conditions
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Major Bleeding

Intervention / Treatment
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* Other: None (Observational study)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥18 years on the index date Admitted to the hospital with an acute major bleeding or developed an acute bleeding while already in hospital Ongoing treatment with a Factor Xa inhibitor before the index date Provided signed and dated informed consent or able to obtain a waiver In addition, for cohort B: - Administered reversal or replacement therapy Exclusion Criteria: Pregnant women Patients enrolled in any interventional trial that includes reversal/replacement agents In addition, for cohort B: Use of vitamin K antagonists, dabigatran, prothrombin complex concentrates or recombinant factor VII, or transfusion of whole blood or plasma within the preceding 7 days of the index event As judged by the investigator, if it is deemed undesirable for the patient to participate in the study or participant is unlikely to comply with study procedures, and requirements Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 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 |
| --- | --- |
| Cohort A - Historical Cohort<br>Cohort A will comprise of approximately 2000 patients admitted for major bleedings in the presence of Factor Xa inhibitor treatment during a defined period (up to 2 years prior to commencing enrolment of patients in Cohort B). Patients who developed major bleeding in the presence of Factor Xa inhibitor treatment while already admitted in hospitals will also be included. Patients may or may not have received a reversal/replacement therapy. Patients are followed in medical charts from admission to discharge. | Other: None (Observational study)<br>* Not Applicable since Observational Study<br>* Other names: Observational Study;|
| Cohort B - Prospective Cohort<br>Cohort B will enrol approximately 2000 patients who were administered any reversal or replacement agent during the acute care phase for a major bleeding in the presence of Factor Xa inhibitor treatment at the participating sites. Patients will be followed up to three months after administration of reversal or replacement therapy. | Other: None (Observational study)<br>* Not Applicable since Observational Study<br>* Other names: Observational Study;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demographics (age in years) | Summary statistics will be used to describe demographics. | Cohort A: from admission for the bleeding (index date) until hospital discharge. Cohort B: from index date (time of administration of reversal/replacement agent) to hospital discharge (up to 90 days) | 
| Demographics (sex) | Summary statistics will be used to describe demographics. | Cohort A: from admission for the bleeding (index date) until hospital discharge. Cohort B: from index date (time of administration of reversal/replacement agent) to hospital discharge (up to 90 days) | 
| Demographics (ethnicity) | Summary statistics will be used to describe demographics. | Cohort A: from admission for the bleeding (index date) until hospital discharge. Cohort B: from index date (time of administration of reversal/replacement agent) to hospital discharge (up to 90 days) | 
| Demographics (race) | Summary statistics will be used to describe demographics. | Cohort A: from admission for the bleeding (index date) until hospital discharge. Cohort B: from index date (time of administration of reversal/replacement agent) to hospital discharge (up to 90 days) | 
| Demographics (payer type) | Summary statistics will be used to describe demographics. | Cohort A: from admission for the bleeding (index date) until hospital discharge. Cohort B: from index date (time of administration of reversal/replacement agent) to hospital discharge (up to 90 days) | 
| Clinical presentation | Summary statistics will be used to describe clinical presentation of patients. | Cohort A: from admission for the bleeding (index date) until hospital discharge. Cohort B: from index date (time of administration of reversal/replacement agent) to hospital discharge (up to 90 days) | 
| Healthcare interventions provided during acute care phase | To describe the health care interventions provided during acute care phase in patients with major bleedings in the context of Factor Xa inhibitor treatment. | Cohort A: from admission for the bleeding (index date) until hospital discharge. Cohort B: from index date (time of administration of reversal/replacement agent) to hospital discharge (up to 90 days) | 
| In-hospital outcomes | To describe the in-hospital outcomes in patients with major bleedings in the context of Factor Xa inhibitor treatment. | Cohort A: from admission for the bleeding (index date) until hospital discharge. Cohort B: from index date (time of administration of reversal/replacement agent) to hospital discharge (up to 90 days) | 
| Timing of administration of reversal/replacement agents since admission/bleed onset | To describe the timing of administration of reversal/replacement agents from admission/bleed onset. | Cohort A: from admission for the bleeding (index date) until hospital discharge. Cohort B: from index date (time of administration of reversal/replacement agent) to hospital discharge (up to 90 days) | 
| Short Form Health Survey (SF-36) - Cohort B | The 36-Item Short Form Health Survey Version 2 (SF-36 v2) is a standardized, patient-administered instrument across eight domains (including physical functioning, role limitations due to physical health, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health). Each subscale is scored separately, and the scores range from 0 to 100. Higher scores indicate better health-related quality of life. | Cohort B: from index date (time of administration of reversal/replacement agent) to hospital discharge (up to 90 days) | 
| 5-Dimension Health Questionnaire 5 Level (EQ-5D-5L) - Cohort B | The EuroQoL EQ-5D-5L questionnaire measures generic Health-Related Quality of Life (HRQoL) and contains questions on five dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety/depression. Each subscale is scored based on 5 levels of severity (no problems, slight problems, moderate problems, severe problems, and unable to perform or extreme problems). It can be converted into a single numeric score and has been translated and validated in numerous countries. The EQ-5D-5L scoring system assigns a utility value to each health state based on population preferences. The utility values range from -0.594 (representing the worst health state possible) to 1.000 (representing perfect health). | Cohort B: from index date (time of administration of reversal/replacement agent) to hospital discharge (up to 90 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical outcomes - Cohort B | To describe the clinical outcomes in patients who experienced major bleedings in the context of Factor Xa inhibitor treatment and administered reversal/replacement therapy. | At 30 days post index (date of administration of reversal/replacement agents) | 
| Timing of administration of reversal/replacement therapy since admission/bleed onset - Cohort B | To describe the timing of administration of reversal replacement therapy since admission/bleed onset. | At 30 days post index (date of administration of reversal/replacement agents) | 
| Short Form Health Survey (SF-36) - Cohort B | The 36-Item Short Form Health Survey Version 2 (SF-36 v2) is a standardized, patient-administered instrument across eight domains (including physical functioning, role limitations due to physical health, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health. Each subscale is scored separately, and the scores range from 0 to 100. Higher scores indicate better health-related quality of life. | 30 days post index (date of administration of reversal/replacement agents) | 
| 5-Dimension Health Questionnaire 5 Level (EQ-5D-5L) - Cohort B | The EuroQoL EQ-5D-5L questionnaire measures generic HRQoL and contains questions on five dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety/depression. Each subscale is scored based on 5 levels of severity (no problems, slight problems, moderate problems, severe problems, and unable to perform or extreme problems). It can be converted into a single numeric score and has been translated and validated in numerous countries. The EQ-5D-5L scoring system assigns a utility value to each health state based on population preferences. The utility values range from -0.594 (representing the worst health state possible) to 1.000 (representing perfect health). | 30 days post index (date of administration of reversal/replacement agents) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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real-world evidence, Factor Xa inhibitor treatment, reversal/replacement therapy