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

• ClinicalTrials.gov Identifier: NCT02866838
• Recruitment Status: Completed
• First Posted: August 15, 2016
• Last Update Posted: December 14, 2021
• Sponsor: University Hospital, Basel, Switzerland
• Collaborator: Swiss National Science Foundation
• Information provided by (Responsible Party): University Hospital, Basel, Switzerland

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Intracerebral Hemorrhage	Drug: Tranexamic acid; Drug: Saline 0.9%	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Treatment of Intracerebral Hemorrhage in Patients on Non-vitamin K Antagonist Oral Anticoagulants (NOAC) With Tranexamic Acid
• Actual Study Start Date: December 2016
• Actual Primary Completion Date: September 30, 2021
• Actual Study Completion Date: September 30, 2021

Arms and Interventions

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 Name: Cyklokapron
Placebo Comparator: Placebo; Saline 0.9% given in identical dosage as experimental	Drug: Saline 0.9%; intravenous

Outcome Measures

Primary Outcome Measures :

1. Hematoma expansion [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Switzerland

Stroke Center, University Hospital Basel

Basel, Switzerland, 4031

Sponsors and Collaborators

University Hospital, Basel, Switzerland

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

More Information

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT02866838
• Other Study ID Numbers: BASEC 2016-01251
• First Posted: August 15, 2016
• Last Update Posted: December 14, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Basel, Switzerland:

Tranexamic acid; NOAC; Direct Oral Anticoagulant (DOAC); Direct oral anticoagulants; Non-Vitamin K antagonist oral anticoagulants

Additional relevant MeSH terms:

Cerebral Hemorrhage; Hemorrhage; Pathologic Processes; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Tranexamic Acid; Antifibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Hemostatics; Coagulants