Effect of Xenon on Brain Injury After Aneurysmal Subarachnoid Hemorrhage

NCT04696523 | Recruiting Phase 2 DMC

• 2 other identifiers: 109/2019 Xe-SAH2019-001542-17
• Study Type: interventional
• Target: 160
• Locations: 2 countries
• Sites: 7

Brief Summary

An investigator-initiated clinical drug study Main Objective: To explore neuroprotective properties of xenon in patients after aneurysmal subarachnoid hemorrhage (SAH). Primary endpoint: Global fractional anisotropy of white matter of diffusion tensor imaging (DTI). Hypothesis: White matter damage is less severe in xenon treated patients, i.e. global fractional anisotropy is significantly higher in the xenon group than in the control group as assessed with the 1st magnetic resonance imaging (MRI). After confirmation of aSAH and obtaining a signed assent subjects will be randomized to the following groups: Control group: Standard of Care (SOC) group: Air/oxygen and Normothermia 36.5-37.5°C; Xenon group: Normothermia 36.5-37.5°C +Xenon inhalation in air/oxygen for 24 hours. Brain magnetic resonance imaging techniques will be undertaken to evaluate the effects of the intervention on white and grey matter damage and neuronal loss. Neurological outcome will be evaluated at 3, 12 and 24 months after onset of aSAH symptoms Investigational drug/treatment, dose and mode of administration: 50±2 % end tidal concentration of inhaled xenon in oxygen/air. Comparative drug(s)/placebo/treatment, dose and mode of administration: Standard of care treatment according to local and international consensus reports. Duration of treatment: 24 hours Assessments: Baseline data Information that characterizes the participant's condition prior to initiation of experimental treatment is obtained as soon as is clinically reasonable. These include participant demographics, medical history, vital signs, oxygen saturation, and concentration of oxygen administered. Acute data The collected information will contain quantitative and qualitative data of aSAH patients, as recommended by recent recommendations of the working group on subject characteristics, and including all relevant Common Data Elements (CDE) can be applied. Specific definitions, measurements tools, and references regarding each SAH CDE can be found on the weblink here: https://www.commondataelements.ninds.nih.gov/SAH.aspx#tab=Data\_Standards.

Conditions

Subarachnoid Hemorrhage, Aneurysmal; Cerebral Injury; Cerebral Ischemia; Cerebral Infarction; Cardiac Event; Cardiac Failure

Keywords

xenon, neuroprotection, aneurysmal subarachnoid hemorrhage

Outcome Measures

Primary Outcomes (1)

• Fractional anisotropy of the white matter

  Global fractional anisotropy of white matter of diffusion tensor imaging (DTI). Hypothesis: White matter damage is less severe in xenon treated patients, i.e. global fractional anisotropy is significantly higher in the xenon group than in the control group as assessed with the 1st MRI.

  48-96 hours after start of aSAH symptoms

Secondary Outcomes (30)

• Fractional anisotropy of white matter at cerebellum and/or at corpus callosum as assessed with the 1st MRI.

  48-96 hours after start of aSAH symptoms

• Safety and tolerability of xenon

  during the follow-up of one year

• Composite of radiological early brain injury (EBI) and delayed cerebral ischemia (DCI)

  EBI: within first 72 hours after start of aSAH symptoms; mRS at 3 months and at 1 year and at 2 years after onset of aSAH symptoms

• Neurogenic Stress Cardiomyopathy and Stunned Myocardium

  follow-up of 1 year

• Intracerebral pressure (ICP)

  during ICU stay up to 14 days after onset of aSAH symptoms

Study Arms (2)

Air/Oxygen

ACTIVE COMPARATOR

Control arm: air/oxygen with standard of care

Drug: air/oxygen

xenon

EXPERIMENTAL

Xenon arm: xenon inhalation in air/oxygen with standard of care

Drug: Xenon

Interventions

Xenon DRUG

Xenon arm will be treated with xenon inhalation with endtidal concentration of 50 % in air/oxygen and with standard of care

xenon

air/oxygen DRUG

Control group will be treated with air/oxygen

Air/Oxygen

Eligibility Criteria

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

You may qualify if:

• Informed consent obtained from the next of kin or legal representative
• Aneurysmal subarachnoid hemorrhage visible on CTA or DSA.
• Deterioration of consciousness to Hunt-Hess 3-5
• Age of ≥ 18 years
• Intubated.
• GCS 3-12 obtained off neuromuscular blocking agents
• Xenon treatment can be started within 6 hours after onset of SAH symptoms

You may not qualify if:

• Acute or chronic traumatic brain injury
• Maximum diameter of intracerebral hemorrhage \> 2.5 cm
• Pneumothorax or pneumomediastinum,
• Acute lung injury requiring ≥ 60% FIO2 (fraction of inspired oxygen).
• Systolic arterial pressure \< 80 mmHg or mean arterial pressure \< 60 mmHg for over 30 min period
• Bilaterally fixed and dilated pupils
• Positive pregnancy test, known pregnancy, or current breast-feeding
• Neurological deficiency due to traumatic brain injury or other neurological illness
• Imminent death or current life-threatening disease
• Current enrollment in another interventional study
• The subject is known to have clinically significant laboratory abnormality, medical condition (such as decompensated liver disease or severe chronic obstructive pulmonary disease), or social circumstance that, in the investigator's opinion, makes it inappropriate for the subject to participate in this clinical trial.
• Presence of implants or foreign bodies which are not known to be MRI safe

Sponsors & Collaborators

• Turku University Hospital: lead
• Academy of Finland: collaborator

Study Sites (7)

Aalto University School of Science

Helsinki, Helsinki, Finland

NOT YET RECRUITING

Kuopio University Hospital

Kuopio, Kuopio, Finland

NOT YET RECRUITING

Tampere University Hospital

Tampere, Pirkanmaa, Finland

NOT YET RECRUITING

Turku University Hospital

Turku, Turku, 20521, Finland

RECRUITING

Elomatic

Turku, Turku, 20810, Finland

NOT YET RECRUITING

University of Turku, Turku Bioscience, Analysis of the metabolomics

Turku, Turku, Finland

NOT YET RECRUITING

Örebro University

Örebro, Örebro County, Sweden

NOT YET RECRUITING

Related Publications (3)

• Laitio R, Hynninen M, Arola O, Virtanen S, Parkkola R, Saunavaara J, Roine RO, Gronlund J, Ylikoski E, Wennervirta J, Backlund M, Silvasti P, Nukarinen E, Tiainen M, Saraste A, Pietila M, Airaksinen J, Valanne L, Martola J, Silvennoinen H, Scheinin H, Harjola VP, Niiranen J, Korpi K, Varpula M, Inkinen O, Olkkola KT, Maze M, Vahlberg T, Laitio T. Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2016 Mar 15;315(11):1120-8. doi: 10.1001/jama.2016.1933.

  PMID: 26978207 BACKGROUND

• Arola O, Saraste A, Laitio R, Airaksinen J, Hynninen M, Backlund M, Ylikoski E, Wennervirta J, Pietila M, Roine RO, Harjola VP, Niiranen J, Korpi K, Varpula M, Scheinin H, Maze M, Vahlberg T, Laitio T; Xe-HYPOTHECA Study Group. Inhaled Xenon Attenuates Myocardial Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: The Xe-Hypotheca Trial. J Am Coll Cardiol. 2017 Nov 28;70(21):2652-2660. doi: 10.1016/j.jacc.2017.09.1088.

  PMID: 29169472 BACKGROUND

• Laaksonen M, Rinne J, Rahi M, Posti JP, Laitio R, Kivelev J, Saarenpaa I, Laukka D, Frosen J, Ronkainen A, Bendel S, Langsjo J, Ala-Peijari M, Saunavaara J, Parkkola R, Nyman M, Martikainen IK, Dickens AM, Rinne J, Valtonen M, Saari TI, Koivisto T, Bendel P, Roine T, Saraste A, Vahlberg T, Tanttari J, Laitio T. Effect of xenon on brain injury, neurological outcome, and survival in patients after aneurysmal subarachnoid hemorrhage-study protocol for a randomized clinical trial. Trials. 2023 Jun 19;24(1):417. doi: 10.1186/s13063-023-07432-8.

  PMID: 37337295 DERIVED

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Brain Injuries; Brain Ischemia; Cerebral Infarction; Cardiovascular Diseases; Heart Failure

Interventions

Xenon

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Brain Infarction; Stroke; Infarction; Ischemia; Necrosis; Heart Diseases

Intervention Hierarchy (Ancestors)

Noble Gases; Elements; Inorganic Chemicals; Gases

Study Officials

• Timo T Laitio, MD, PhD

  Turku University Hospital and University of Turku, Turku , Finland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Timo T Laitio, MD, PhD

CONTACT

+358504653201; timo.laitio@tyks.fi

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: single blind; participants, outcomes assessors are blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: associate professor, head physician

Model Details: Study design is a single blind randomized two-armed parallel follow-up study.

Study Record Dates

• First Submitted: January 2, 2021
• First Posted: January 6, 2021
• Study Start: April 22, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: May 1, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: data will be available 6 months after the Article's pulication and will be available for 12 months from publication.
• Access Criteria: Requests and proposals should be directed to timo.laitio@elisanet.fi. To gain access, data requestors will need to sign a data access agreement.

Locations

FI (6); SE (1)