Predicting Outcomes in ICH Patients on Direct Factor Xa Inhibitors

NCT06383741 | Recruiting

• 1 other identifier: 2023-00541
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This study focuses on direct factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) and the thrombin inhibitor dabigatran, commonly used for stroke prevention in atrial fibrillation. Despite lower intracranial bleeding risks with these drugs, around 0.2-1.0% of patients annually experience intracranial hemorrhage (ICH), predominantly intracerebral. Treatment options for factor-Xa inhibitor-associated ICH, such as prothrombin complex concentrate (PCC) and andexanet alfa, lack direct comparison evidence except for ongoing trials like ANNEXA-I. This trial assesses hemostatic efficacy and 30-day functional outcomes but leaves gaps regarding anticoagulant activity's role and long-term effects, especially in patients presenting late after drug intake. The measurement of anti-FXa levels helps guide decisions, yet their link to hematoma expansion remains unknown. Efforts to streamline measurement within 30 minutes for acute decisions have shown variability in levels, with some patients exhibiting high levels even beyond 12 hours post-intake. This lack of data poses challenges, particularly for patients potentially benefiting from treatment beyond the current strict time window. Early hematoma expansion strongly predicts poor outcomes, but preventing it faces challenges like recurrent events (up to 5% by 3 months) and rehabilitation intensity, potentially negating its benefits. The ANNEXA-I trial evaluates short-term outcomes, highlighting the need for additional data to comprehend long-term ICH prognosis. The study's objectives involve linking hematoma expansion to anti-FXa levels, determining late-presenting patients' risk of expansion, and identifying predictors of favorable outcomes at 3, 6, and 12 months. Primary endpoints include functional outcomes, while secondary ones encompass expansion rates, anticoagulant activity, and various events at 12 months. This research aims to bridge gaps in understanding factor-Xa inhibitor-related ICH, addressing both immediate and prolonged outcomes to enhance clinical decision-making.

Conditions

Intra Cerebral Hemorrhage

Outcome Measures

Primary Outcomes (3)

• Good functional outcome

  Good functional outcome: defined as mRS 0-3

  At 3 months

• Good functional outcome

  Good functional outcome: defined as mRS 0-3

  At 6 months

• Good functional outcome

  Good functional outcome: defined as mRS 0-3

  At 12 months

Secondary Outcomes (9)

• Haematoma expansion

  Up to 72hours after baseline imaging

• Number of patients with significant anticoagulant activity arriving late

  At baseline visit (i.e. hospitalisation)

• Absolute haematoma expansion (in ml) between baseline and follow-up imaging

  At 3 and 12 months follow-up hospital visit

• Symptomatic haematoma expansion

  At 3 and 12 months follow-up hospital visit

• Resumption of anticoagulant therapy after haemorrhage

  At 3, 6 and 12 months

Study Arms (1)

ICH study cohort

Patients with intracerebral haemorrhage associated with factor Xa-inhibitor treatment treated at one of the participating centres.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population comprises individuals admitted to stroke units or stroke centers who experienced intracranial bleeding while on prior direct oral anticoagulant (DOAC) therapy, specifically factor Xa inhibitors such as apixaban, edoxaban, rivaroxaban, and the direct thrombin inhibitor dabigatran. These patients suffered from direct factor Xa inhibitor-associated intracerebral haemorrhage (ICH).

You may qualify if:

• Imaging proven intracerebral haemorrhage
• Prior therapy with a factor Xa-inhibitor (apixaban, edoxaban or rivaroxaban), not paused for medical/non-medical reasons for more than 48 hours prior to symptom onset
• Drug-specific calibrated anti-FXa levels measured on admission
• Informed consent (by patient, next-of-kin or deferred consent)

You may not qualify if:

• Additional treatment with Vitamin K antagonist or dabigatran

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Insel Gruppe AG, Inselspital Bern

Bern, 3010, Switzerland

RECRUITING

MeSH Terms

Conditions

Cerebral Hemorrhage

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David J. Seiffge

  Insel Gruppe AG, University Hospital Bern

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David J. Seiffge

CONTACT

+41 31 66 4 12 31; david.seiffge@insel.ch

Janis P. Rauch

CONTACT

janispatricia.rauch@insel.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2024
• First Posted: April 25, 2024
• Study Start: July 10, 2023
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: April 25, 2024

Record last verified: 2024-04

Locations

CH (1)