Andexanet Alfa: Non-interventional Study in Stroke Units in Germany (DE) (ASTRO-DE)

The multicenter, prospective, observational, non-interventional study conducted in German Stroke Units is investigating patients with intracranial hemorrhage (ICH) under effective anticoagulation with rivaroxaban or apixaban.

The aim of the study is to analyze under routine conditions wether the volume increase of ICH under treatment with rivaroxaban and apixaban can be reduced with the antidote andexanet alfa. Thus, data of patients under effective treatment with rivaroxaban or apixaban and treated with andexanet alfa at baseline will be assessed at the time of onset of ICH, during the hospital stay and during a follow-up by telephone at 30 and 90 days after hospital discharge.

The main objective is defined as the change in size or volume of the hematoma by computed tomography (CT) or magnetic resonance imaging (MRI) in patients with ICH under effective treatment with rivaroxaban and apixaban, who are treated with andexanet alfa. Further objectives comprise evaluations concerning the functional status according to modified Rankin Scale (mRS), changes in the National Institutes of Health Stroke Scale (NIHSS), and occurrences of ICH or new intraventricular bleeding as well as mortality rates.

Study Overview

• Status: Recruiting
• Conditions: Intracranial Hemorrhages

• Study Type: Observational
• Enrollment (Anticipated): 140

Contacts and Locations

• Study Contact: Name: Hans Diener, Prof. Dr.; Phone Number: 6540 +49 201 723; Email: hans.diener@uk-essen.de

Study Locations

• Germany
  • Hannover, Germany, 30625
    • Recruiting
    • Medizinische Hochschule Hannover
    • Contact: Karin Weißenborn, Prof.
  • Tübingen, Germany, 72076
    • Recruiting
    • Universitätsklinikum Tübingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with anticoagulating therapy with rivaroxaban or apixaban admitted with a clinically symptomatic ICH will be included in the study if they have been treated with andexanet alfa. A repeat CT or MRI between 12-72h after initial imaging to assess size and volume of bleeding corresponds to the standard treatment.

The option to include patients under anticoagulating therapy edoxaban will be evaluated during the course of the study in case a marketing authorization of andexanet alfa for patients under edoxaban will be received.

Description

Inclusion Criteria:

• Age ≥18 years at enrollment
• Patients willing and able to provide written informed consent for data transmission. For patients who are not legally competent to sign this informed consent for data transmission exceptions/special cases are defined (details provided in the study protocol)
• Patients with primary intracranial hemorrhage as confirmed with CT or MRI.
• Patients under effective anticoagulation treatment with rivaroxaban or apixaban at the time of admission, according to the judgement of treating physician and determined using Point-of-care (PoC) anti-factor Xa (fXa) assays or laboratory-based anti-fXa measurement.
• Patients treated with andexanet alfa
• Signed informed consent as soon as possible after start of symptoms of initial ICH event, but before discharge

Exclusion Criteria:

• Start of symptoms of initial ICH event > 24 h before admission to hospital

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patient group; Patients under effective anticoagulation with rivaroxaban or apixaban and treated with andexanet alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in size (specified as ml or cm^3) of the intracranial bleeding evaluated by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)	The primary endpoint is the change in size (specified as ml or cm^3) of the intracranial bleeding evaluated by first CT or MRI between 12-72 hours after initial CT or MRI; further imaging in case of worsened health condition	12-72 hours after initial CT or MRI, further imaging in case of worsened health condition

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional status according to modified Rankin Scale (mRS)	Functional status acc. to modified Rankin Scale (mRS) before ICH, at admission, at discharge, after 30 days, and after 90 days. The mRS ranges from grade 0 (no symptoms) to grade 6 (dead)	before ICH, at admission, at discharge, after 30 days, and after 90 days
Mortality rate	Mortality rate after 7, 30 and 90 days, and intra-hospital mortality rate	after 7, 30 and 90 days und during hospital stay
Rate of worsened health condition	Rate of worsened health condition defined as change in NIHSS of ≥4 pts compared to initial NIHSS or worsening of NIHSS level of consciousness ≥1 point or increase of the volume of the intracranial bleeding or new intraventricular bleeding or death	At hospital admission and additionally at 24 hours and 72 hours after admission
Change in severity of stroke	Change in severity of stroke based on the National Institutes of Health Stroke Scale (NIHSS) 72 hours after admission	72 hours after admission
Assessment of effective anticoagulation at baseline	Assessment of effective anticoagulation at baseline using PoC anti-fXa assay, intra-hospital decision making for Andexanet alfa administration	at baseline
Clinical course and outcomes of patients	Hemostasis will be assessed by coagulation parameters (activated partial thrombin time (aPTT), thrombin time (TT), International Normalized Ratio (INR)) at admission, re-bleeding and thrombotic events (e.g. myocardial infarction, ischemic stroke, deep vein thrombosis) will be assessed by AE reporting performed from admission to hospital to discharge	Coagulation parameters will be recorded at hospital admission. Thrombotic events and re-bleeding will be recorded from the date of hospital admission until discharge. The average length of hospital stay is expected to be 10 days
Re-dosing and re-anticoagulation therapy	Resumption of antithrombotic therapy in hospital (incl. type, start date and dose of anticoagulation therapy)	The assessement of re-dosing and re-anticoagulation therapy will take place from the date of hospital admission until the date of discharge. The average length of hospital stay is expected to be 10 days.
Health care resource utilization (including ICU length of stay)	Data regarding ICU length of stay and on resource utilization (Intubated on arrival, Mechanical ventilation, ICH-evacuation surgery, External ventricular drainage, Intraventricular lysis, Osmotherapy)	Will be recorded during hospital stay until the date of discharge.The average length of hospital stay is expected to be 10 days.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety endpoints	Assessment of non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	Will be recorded at hospital admission, at 24 and 72 hours after admission, at discharge. The average length of hospital stay is expected to be 10 days (depends on the severity of disease and cannot be specifically defined).

Collaborators and Investigators

• Sponsor: University Hospital, Essen

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 8, 2021
• Primary Completion (ANTICIPATED): July 1, 2024
• Study Completion (ANTICIPATED): December 1, 2024

Study Registration Dates

• First Submitted: October 12, 2021
• First Submitted That Met QC Criteria: November 8, 2021
• First Posted (ACTUAL): November 19, 2021

Study Record Updates

• Last Update Posted (ACTUAL): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Rivaroxaban; Anticoagulation; Apixaban; Intracranial bleeding; Andexanet-alfa
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hemorrhage; Intracranial Hemorrhages
• Other Study ID Numbers: ASTRO-DE

Drug and device information, study documents

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