Treatment of Intracerebral Hemorrhage in Patients on Non-vitamin K Antagonist

Phase 2

Completed

• Conditions: Intracerebral Hemorrhage
• Interventions: Drug: Tranexamic acid; Drug: Saline 0.9%

• Registration Number: NCT02866838
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

Novel, non-vitamin K antagonist oral anticoagulants (NOAC) target selected players in the coagulation cascade as the direct thrombin inhibitor dabigatran and the factor Xa-inhibitors apixaban and rivaroxaban. Intracerebral hemorrhage (ICH) is the most feared complication of NOAC treatment (NOAC-ICH).

Outcome of NOAC-ICH can be devastating and is a major cause of death and disability. There is no proven treatment for NOAC-ICH. Hematoma expansion (HE) is associated with unfavorable outcome. Tranexamic acid (TA) is an anti-fibrinolytic drug that is used in a number of bleeding conditions other than ICH.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-08-10
• Study First Submitted QC: 2016-08-10
• Study First Posted: 2016-08-15
• Study Start: 2016-12
• Primary Completion: 2021-09-30
• Status Verified: 2022-03
• Study Completion: 2022-03-22
• Last Update Submitted: 2022-03-22
• Last Update Posted: 2022-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

• Acute intracerebral hemorrhage (symptom onset <12h)
• Prior treatment with a novel direct oral anticoagulant (apixaban, dabigatran, edoxaban or rivaroxaban; last intake <48hours or proven NOAC activity by relevant coagulation assays)
• Age >18 years, No upper age limit
• Informed consent has been received in accordance to local ethics committee requirements

Exclusion Criteria

• Severe pre-morbid disability (modified Rankin scale >4)
• Anticoagulation with Vitamin K antagonists (VKA) (recent intake)
• Secondary intracerebral hemorrhage (e.g. arteriovenous malformation (AVM), tumor, trauma) Note it is not necessary for investigators to exclude underlying structural abnormality prior to enrolment, but where an underlying structural abnormality is already known, these patients should not be recruited.
• Glasgow coma scale <5
• pregnancy
• Planned neurosurgical hematoma evacuation within 24 hours (before follow-up imaging)
• Pulmonary embolism/deep vein thrombosis within the last 2 weeks.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tranexamic acid	Tranexamic acid	Intravenous tranexamic acid: 1g loading dose given as 100 mls infusion over 10 minutes, followed by another 1g in 250 mls infused over 8 hours.
Placebo	Saline 0.9%	Saline 0.9% given in identical dosage as experimental

Primary Outcome Measures

Name	Time	Method
Hematoma expansion	up to 27 hours	Change in ICH-volume between baseline CT and follow-up-CT at 24 ± 3 hours of 33% relative or 6ml absolute increase

Secondary Outcome Measures

Name	Time	Method
Absolute ICH growth volume by 24 ± 3 hours, adjusted for baseline ICH volume	up to 27 hours
modified Rankin Scale (mRS) 0-4 at month 3;	3 months
mRS 0-3 at month 3;	3 months
Categorical shift in mRS at month 3	3 months
mortality due to any cause at month 3	3 months
In-hospital mortality	baseline until discharge from hospital (stay at hospital lasts on an average of 10 days)
Symptomatic HE defined as HE and additionally a neurological deterioration of NIHSS >4 points or Glasgow Coma Scale (GCS) >2 points	up to 27 hours
number of major thromboembolic events (myocardial infarction, ischemic stroke, pulmonary embolism - safety endpoints)	3 months
number of neurosurgical interventions (including craniectomy, external ventricular drain (EVD), hematoma evacuation)	3 months

Trial Locations

Locations (1)

Stroke Center, University Hospital Basel; 🇨🇭 Basel, Switzerland