Treatment of Intracerebral Hemorrhage in Patients on Non-vitamin K Antagonist (TICH-NOAC)

Treatment of Intracerebral Hemorrhage in Patients on Non-vitamin K Antagonist Oral Anticoagulants (NOAC) With Tranexamic Acid

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.

Study Overview

• Status: Completed
• Conditions: Intracerebral Hemorrhage
• Intervention / Treatment: Drug: Tranexamic acid; Drug: Saline 0.9%

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Stroke Center, University Hospital Basel

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: Tranexamic acid; intravenous; Other Names: Cyklokapron
PLACEBO_COMPARATOR: Placebo; Saline 0.9% given in identical dosage as experimental	Drug: Saline 0.9%; intravenous

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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)
Absolute ICH growth volume by 24 ± 3 hours, adjusted for baseline ICH volume	up to 27 hours
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

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Swiss National Science Foundation
• Investigators: Study Chair: Philippe Lyrer, MD, Stroke Center and Neurology, University Hospital Basel; Study Chair: Stefan Engelter, MD, Stroke Center and Neurology, University Hospital Basel

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2016
• Primary Completion (ACTUAL): September 30, 2021
• Study Completion (ACTUAL): March 22, 2022

Study Registration Dates

• First Submitted: August 10, 2016
• First Submitted That Met QC Criteria: August 10, 2016
• First Posted (ESTIMATE): August 15, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 4, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: NOAC; Tranexamic acid; Direct oral anticoagulants; Direct Oral Anticoagulant (DOAC); Non-Vitamin K antagonist oral anticoagulants
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: BASEC 2016-01251

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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