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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Major Bleeding
• Intervention / Treatment: Other: None (Observational study)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 4000

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Germany
  • Altenburg, Germany
    • Recruiting
    • Research Site
  • Bad Neustadt/Saale, Germany
    • Not yet recruiting
    • Research Site
  • Berlin, Germany
    • Recruiting
    • Research Site
  • Berlin, Germany
    • Not yet recruiting
    • Research Site
  • Bochum, Germany
    • Not yet recruiting
    • Research Site
  • Bonn, Germany
    • Not yet recruiting
    • Research Site
  • Jena, Germany
    • Not yet recruiting
    • Research Site
  • Koln, Germany
    • Not yet recruiting
    • Research Site
  • Leipzig, Germany
    • Not yet recruiting
    • Research Site
  • Lubeck, Germany
    • Not yet recruiting
    • Research Site
  • Lubeck, Germany
    • Recruiting
    • Research Site
  • Osnabruck, Germany
    • Not yet recruiting
    • Research Site
  • Potsdam, Germany
    • Not yet recruiting
    • Research Site
  • Saarbrucken, Germany
    • Not yet recruiting
    • Research Site
• Japan
  • Asahikawa, Japan
    • Recruiting
    • Research Site
  • Hitachi, Japan
    • Recruiting
    • Research Site
  • Izumo, Japan
    • Not yet recruiting
    • Research Site
  • Kagoshima, Japan
    • Recruiting
    • Research Site
  • Kitakyushu, Japan
    • Recruiting
    • Research Site
  • Mitaka, Japan
    • Not yet recruiting
    • Research Site
  • Saga, Japan
    • Recruiting
    • Research Site
  • Shimotsuke, Japan
    • Not yet recruiting
    • Research Site
  • Tachikawa, Japan
    • Recruiting
    • Research Site
  • Tokyo, Japan
    • Not yet recruiting
    • Research Site
• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • Research Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • Research Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • Research Site
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Not yet recruiting
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Research Site
  • New York
    • Stony Brook, New York, United States, 11794
      • Not yet recruiting
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Not yet recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients aged ≥18 years admitted to hospital with an acute major bleeding or developed an acute bleeding while already in hospital and received ongoing treatment with a Factor Xa inhibitor before the index date.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort A - Historical Cohort; 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); Not Applicable since Observational Study; Other Names: Observational Study
Cohort B - Prospective Cohort; 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); Not Applicable since Observational Study; Other Names: Observational Study

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2023
• Primary Completion (Estimated): March 11, 2025
• Study Completion (Estimated): March 11, 2025

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: November 17, 2023
• First Posted (Actual): November 28, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: real-world evidence; Factor Xa inhibitor treatment; reversal/replacement therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage
• Other Study ID Numbers: D9603R00003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No