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

NCT02866838 | Completed Phase 2 DMC

• 1 other identifier: BASEC 2016-01251
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Intracerebral Hemorrhage

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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)

Study Arms (2)

Tranexamic acid

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Saline 0.9% given in identical dosage as experimental

Drug: Saline 0.9%

Interventions

Tranexamic acid DRUG

intravenous

Also known as: Cyklokapron

Tranexamic acid

Saline 0.9% DRUG

intravenous

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Swiss National Science Foundation: collaborator

Study Sites (1)

Stroke Center, University Hospital Basel

Basel, 4031, Switzerland

Location

Related Publications (2)

• Eilertsen H, Menon CS, Law ZK, Chen C, Bath PM, Steiner T, Desborough MJ, Sandset EC, Sprigg N, Al-Shahi Salman R. Haemostatic therapies for stroke due to acute, spontaneous intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Oct 23;10(10):CD005951. doi: 10.1002/14651858.CD005951.pub5.

  PMID: 37870112 DERIVED

• Polymeris AA, Karwacki GM, Siepen BM, Schaedelin S, Tsakiris DA, Stippich C, Guzman R, Nickel CH, Sprigg N, Kagi G, Vehoff J, Barinka F, Thilemann S, Maurer M, Wagner B, Traenka C, Gensicke H, De Marchis GM, Bonati LH, Fischer U, Z'Graggen WJ, Nedeltchev K, Wegener S, Baumgartner P, Engelter ST, Seiffge DJ, Peters N, Lyrer PA; TICH-NOAC Investigators. Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial. Stroke. 2023 Sep;54(9):2223-2234. doi: 10.1161/STROKEAHA.123.042866. Epub 2023 Jul 19.

  PMID: 37466000 DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage

Interventions

Tranexamic Acid; Sodium Chloride

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

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Philippe Lyrer, MD

  Stroke Center and Neurology, University Hospital Basel

  STUDY CHAIR

• Stefan Engelter, MD

  Stroke Center and Neurology, University Hospital Basel

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2016
• First Posted: August 15, 2016
• Study Start: December 1, 2016
• Primary Completion: September 30, 2021
• Study Completion: March 22, 2022
• Last Updated: April 4, 2022

Record last verified: 2022-03

Locations

CH (1)