NCT02684812

Brief Summary

This is a multicenter, prospective, randomized, open-label trial with blinded endpoint (PROBE) assessment. Adult patients with the diagnosis of non-traumatic SAH, as proven by computed tomography (CT) within 24 hours after the onset of headache, will be randomly assigned to the treatment group or the control group. Patients in the treatment group will receive standard treatment with the addition of a bolus of TXA (1 g intravenously) immediately after randomization, followed by continuous infusion of 1 g per 8 hours until the start of aneurysm treatment, or a maximum of 24 hours after the start of medication. Patients in the control group will receive standard treatment without TXA. The primary outcome measure is favorable functional outcome, defined as a score of 0 to 3 on the modified Rankin Scale (mRS), at 6 months after SAH. Primary outcome will be determined by a trial nurse blinded for treatment allocation.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
955

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jul 2012

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 16, 2012

Completed
3.6 years until next milestone

First Submitted

Initial submission to the registry

February 9, 2016

Completed
9 days until next milestone

First Posted

Study publicly available on registry

February 18, 2016

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 29, 2019

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2020

Completed
Last Updated

November 12, 2020

Status Verified

November 1, 2020

Enrollment Period

7 years

First QC Date

February 9, 2016

Last Update Submit

November 10, 2020

Conditions

Subarachnoid Hemorrhage

Keywords

antifibrinolytic therapyrecurrent bleedingtranexamic acid

Outcome Measures

Primary Outcomes (1)

  • Modified Rankin Scale (mRS)

    Good (mRS 0-3) and Poor (mRS 4-6)

    six months

Secondary Outcomes (13)

  • Date and cause of death

    Maximum six month

  • Cause of poor outcome

    six months

  • Rebleed and time interval after first hemorrhage

    six months

  • Thromboembolic events during endovascular treatment

    up to 48 hours

  • Ischemic stroke (Dealyed cerebral ischemia)

    14-20 days

  • +8 more secondary outcomes

Study Arms (2)

Tranexamic Acid

ACTIVE COMPARATOR

Eligible subjects are randomly assigned to immediate administration of TXA (1 g i.v.) after a diagnosis of SAH, as confirmed by CT-scan of the brain, continued by continuous infusion of 1 g per 8 hours to a maximum of 24 hours after start of medication. A maximum of 4 g TXA (1 g bolus + 3x 1 g continuous infusion) can be administered to one patient.

Drug: Tranexamic Acid

Control

NO INTERVENTION

Standard care

Interventions

Tranexamic AcidDRUG

Treatment until aneurysm treatment or maximum dosage of 4 gram

Also known as: Cyklokapron
Tranexamic Acid

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Admission to one of the study centers or their referring hospitals
  • CT-confirmed SAH with most recent ictus less than 24 hours ago Definition: subarachnoid hemorrhage is a bleeding pattern on computed tomography with hyperdensity in the basal cisterns and/or Sylvian or interhemipheric fissures or a intraparenchymal hyperdensity consistent with a hematoma from an anterior, a pericallosal, a posterior or a middle cerebral artery aneurysm.

You may not qualify if:

  • No proficiency of the Dutch or English language
  • No loss of consciousness after the hemorrhage with WFNS grade 1 or 2 on admission in combination with a perimesencephalic hemorrhage Definition: on CT examination presence of hyperdensities exclusively in the basal cisterns maximal extending to the proximal part of the Sylvian fissure or posterior part of the interhemispheric fissure, without evidence for intracerebral or intraventricular haemorrhage (except slight sedimentation)
  • Bleeding pattern on CT compatible with a traumatic SAH
  • Treatment for deep vein thrombosis or pulmonary embolism
  • History of a blood coagulation disorder (a hypercoagulability disorder)
  • Pregnancy checked with a pregnancy test in women in their childbearing period
  • History of severe renal (serum creatinin \>150 mmol/L)
  • History of severe liver failure (AST \> 150 U/l or ALT \> 150 U/l or AF \> 150 U/l or γ-GT \> 150 U/l)
  • Imminent death within 24 hours

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Academic Medical Centre

Amsterdam, Netherlands

Location

Related Publications (7)

  • Germans MR, Post R, Coert BA, Rinkel GJ, Vandertop WP, Verbaan D. Ultra-early tranexamic acid after subarachnoid hemorrhage (ULTRA): study protocol for a randomized controlled trial. Trials. 2013 May 16;14:143. doi: 10.1186/1745-6215-14-143.

    PMID: 23680226RESULT

  • Denneman N, Post R, van Eekelen R, Tjerkstra MA, Kempeneers MA, Labib H, Germans MR, Vergouwen MDI, Jellema K, Koot RW, Kruyt ND, Wolfs JFC, Nanda D, Van Der Pol B, Roks G, De Beer F, Reichman LJA, Brouwers PJAM, Vincent HK 1st, Bienfait HP, Boogaarts HD, Klijn CJM, van den Berg R, Coert BA, Horn J, Majoie CBLM, Rinkel GJE, Roos YBWEM, Vandertop WP, Verbaan D; ULTRA trial study group. Cost-Effectiveness of Ultra-Early Tranexamic Acid as Add-On to Standard Care After Subarachnoid Hemorrhage (ULTRA Trial). Eur J Neurol. 2025 Aug;32(8):e70208. doi: 10.1111/ene.70208.

    PMID: 40843772DERIVED

  • Tjerkstra MA, Post R, Germans MR, Vergouwen MDI, Jellema K, Koot RW, Kruyt ND, Wolfs JFC, De Beer FC, Kieft HH, Nanda D, Van Der Pol B, Roks G, De Beer F, Reichman LJA, Brouwers PJAM, Kwa VIH, Van Der Ree TC, Bienfait HP, Boogaarts HD, Klijn CJ, Visser V, van den Berg R, Coert BA, Horn J, Majoie CBLM, Rinkel GJE, Roos YBWEM, Vandertop WP, Verbaan D; ULTRA trial study group. Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage. Neurology. 2024 Jun 25;102(12):e209169. doi: 10.1212/WNL.0000000000209169. Epub 2024 May 24.

    PMID: 38788175DERIVED

  • Vergouwen MD, Germans MR, Post R, Tjerkstra MA, Coert BA, Rinkel GJ, Peter Vandertop W, Verbaan D. Aneurysm treatment within 6 h versus 6-24 h after rupture in patients with subarachnoid hemorrhage. Eur Stroke J. 2023 Sep;8(3):802-807. doi: 10.1177/23969873231173273. Epub 2023 May 1.

    PMID: 37641555DERIVED

  • Tjerkstra MA, Post R, Germans MR, Vergouwen MDI, Jellema K, Koot RW, Kruyt ND, Willems PWA, Wolfs JFC, de Beer FC, Kieft H, Nanda D, van der Pol B, Roks G, de Beer F, Halkes PHA, Reichman LJA, Brouwers PJAM, Van den Berg-Vos RM, Kwa VIH, van der Ree TC, Bronner I, Bienfait HP, Boogaarts H, Klijn CJM, van den Berg R, Coert BA, Horn J, Majoie CBLM, Rinkel GJE, Roos YBWM, Vandertop WP, Verbaan D; ULTRA investigators. Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post Hoc Analysis of the ULTRA Trial. Neurology. 2022 Dec 5;99(23):e2605-e2614. doi: 10.1212/WNL.0000000000201160.

    PMID: 36266046DERIVED

  • Post R, Germans MR, Tjerkstra MA, Vergouwen MDI, Jellema K, Koot RW, Kruyt ND, Willems PWA, Wolfs JFC, de Beer FC, Kieft H, Nanda D, van der Pol B, Roks G, de Beer F, Halkes PHA, Reichman LJA, Brouwers PJAM, van den Berg-Vos RM, Kwa VIH, van der Ree TC, Bronner I, van de Vlekkert J, Bienfait HP, Boogaarts HD, Klijn CJM, van den Berg R, Coert BA, Horn J, Majoie CBLM, Rinkel GJE, Roos YBWEM, Vandertop WP, Verbaan D; ULTRA Investigators. Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial. Lancet. 2021 Jan 9;397(10269):112-118. doi: 10.1016/S0140-6736(20)32518-6. Epub 2020 Dec 23.

    PMID: 33357465DERIVED

  • Post R, Germans MR, Coert BA, Rinkel GJE, Vandertop WP, Verbaan D. Update of the ULtra-early TRranexamic Acid after Subarachnoid Hemorrhage (ULTRA) trial: statistical analysis plan. Trials. 2020 Feb 18;21(1):199. doi: 10.1186/s13063-020-4118-5.

    PMID: 32070395DERIVED

MeSH Terms

Conditions

Subarachnoid HemorrhageHemorrhage

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Intracranial HemorrhagesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic AcidsAcids, CarbocyclicCarboxylic AcidsOrganic Chemicals

Study Officials

  • William P Vandertop, PhD MD

    Department of Neurosurgery

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
PROBE Design
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Drs.

Study Record Dates

First Submitted

February 9, 2016

First Posted

February 18, 2016

Study Start

July 16, 2012

Primary Completion

July 29, 2019

Study Completion

November 1, 2020

Last Updated

November 12, 2020

Record last verified: 2020-11

Locations

NL(1)