Subarachnoid Hemorrhage, AneurysmalPhase 2Xe-SAHNCT04696523
Effect of Xenon on Brain Injury After Aneurysmal Subarachnoid Hemorrhage
A Phase 2 study testing Xenon and air/oxygen in people with Subarachnoid Hemorrhage, Aneurysmal and Cerebral Injury, run by Turku University Hospital at 7 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Subarachnoid Hemorrhage, Aneurysmal, Cerebral Injury, Cerebral Ischemia
- What is being tested?
- Xenon and air/oxygen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 22 Apr 2025to 31 Dec 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be considered eligible to participate in this study, a SAH subject must meet the inclusion criteria listed below:
- 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
Who cannot join
- An aSAH subject may not be enrolled in the trial if he/she meets any one of the exclusion criteria below:
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
7 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
7 sites in 2 countries
Finland6 sites, 6 recruiting
- Not yet recruiting
Aalto University School of Science
Helsinki, Helsinki
Timo Roine, PhD, timo.roine@gmail.com
- Not yet recruiting
Kuopio University Hospital
Kuopio, Kuopio
Stepani Bendel, stepani.bendel@kuh.fi
- Not yet recruiting
Tampere University Hospital
Tampere, Pirkanmaa
Sari Karlsson, MD, PhD, sari.karlsson@pshp.fi
- Recruiting
Turku University Hospital
Turku, Turku, 20521
Timo T Laitio, MD, PhD, +358504653201, timo.laitio@varha.fi
- Not yet recruiting
Elomatic
Turku, Turku, 20810
Juha Tanttari, MSc
- Not yet recruiting
University of Turku, Turku Bioscience, Analysis of the metabolomics
Turku, Turku
Matej Orešič, PhD, matej.oresic@utu.fi
Alex Dickens, PhD, alex.dickens@utu.fi
Sweden1 site, 1 recruiting
- Not yet recruiting
Örebro University
Örebro, Örebro County
Tuulia Hyötyläinen, PhD
About this study
Official title: Effect of Xenon on Brain Injury, Neurological Outcome and Survival in Patients After Aneurysmal Subarachnoid Hemorrhage
An investigator-initiated clinical drug study
Main Objective:
Read more
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.
Read the detailed description
Assessments of efficacy:
- A brain Computer tomography angiography (CTA) and / or 3 D Digital subtraction angiography (DSA) (whenever possible instead of 2D DSA) will be performed at hospital arrival and whenever clinically indicated.
- 1st 3 Tesla MRI 72 ± 24 hours after onset of aSAH symptoms; 2nd 3 Tesla MRI 42 ± 4 days after onset of aSAH symptoms.
- 3D DSA: Computational fluid dynamic simulations (CFD), artificial intelligence and machine learning.
- Brain Positron emission tomography (PET): The 1st 4 ± 1 weeks and the 2nd at 3 months after onset of aSAH symptoms.
- Biochemical assessment: A blood samples of 20 ml for determination of plasma catecholamines, plasma metabolomics (see details of metabolomics in section 18.4.7), cardiac enzyme release (P-hs-troponin-T and heart fatty-acid binding protein), selected biomarkers will be analysed at intensive crae unit (ICU) arrival and at 24h, at 48h and at 72h after onset of SAH symptoms. In addition, a sample of spinal fluid will be collected through external ventricular drainage (EVD) at ICU arrival or as soon as it is in place and at 24h, at 48h and at 72h after onset of SAH symptoms for assessment of metabolomics
- Electrocardiograph (ECG) at ICU arrival and at 24h, at 48h and at 72h after onset of aSAH symptoms.
- Neurological evaluation: at 3, 12 and at 24 months after aSAH with GOSe, Modified ranking score (mRS).
Statistical methods: 1) Basic statistical tests (t-tests, Mann-Whitney, Chi square, etc); 2) Survival analysis methods; 3) An analysis of variance for repeated measurements; 4) A sample size of 100 is estimated on the basis of a recent studies in SAH patients to provide 80% power with a 2-sided α level of 0.05 to detect a mean difference of 0.02 (SD 0.035) in the global fractional anisotropy of white matter between the xenon group and the control group (98). Accordingly, this mean difference is estimated to have a predictive value for DCI and poor neurological outcome (i.e. mRS 3-6).Significance level of 0.05 and an estimation of 95 % confidence intervals will be used in the statistical analyses.
- Conditions
- Subarachnoid Hemorrhage, Aneurysmal, Cerebral Injury, Cerebral Ischemia, Cerebral Infarction, Cardiac Event, Cardiac Failure
- Being tested
- Xenon, air/oxygen
- Keywords
- xenon, neuroprotection, aneurysmal subarachnoid hemorrhage
- Medical subject headings
- Subarachnoid Hemorrhage, Brain Injuries, Brain Ischemia, Cerebral Infarction, Cardiovascular Diseases, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XenonDrug
Xenon arm will be treated with xenon inhalation with endtidal concentration of 50 % in air/oxygen and with standard of care
air/oxygenDrug
Control group will be treated with air/oxygen
| Study group | Role | What they receive |
|---|---|---|
| Air/Oxygen | Active comparator | Control arm: air/oxygen with standard of care Receives: Drug: air/oxygen |
| xenon | Experimental | Xenon arm: xenon inhalation in air/oxygen with standard of care Receives: Drug: Xenon |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Fractional anisotropy of white matter at cerebellum and/or at corpus callosum as assessed with the 1st MRI.
Measured: 48-96 hours after start of aSAH symptoms
Safety and tolerability of xenon
Safety and tolerability of xenon as assessed with a ratio of adverse events, serious adverse events and suspected unexpected serious adverse reactions (SUSARs) during the follow-up of one year between the xenon group and the control group.
Measured: during the follow-up of one year
Composite of radiological early brain injury (EBI) and delayed cerebral ischemia (DCI)
Composite of radiological EBI (within 72 hours after start of SAH symptoms) and DCI (Criterion of DCI: 1. a new focal neurological deficit (such as hemiparesis, aphasia, apraxia, hemianopia, or neglect) /decrease in level of consciousness (i.e. decrease of at least 2 points on the Glasgow Coma Scale; either on the total score or on one of its individual components, such as eye, motor on either side, or verbal). This should last for at least 1 hour and not is due to other causes (e.g. hydrocephalus, seizures, metabolic derangement, infection, sedation) and is not apparent immediately after aneurysm occlusion, and cannot be attributed to other causes by means of clinical assessment, CT or MRI scanning of the brain, and appropriate laboratory studies, 2. a new infarct on follow-up imaging (i.e. in any of the following: 2nd MRI, CT, CTA, DSA and perfusion CT) after 4 days post-SAH, or 3. both 1 and 2), and poor outcome at 3-months (good: mRS 0-2; poor: mRS 3-6) at 3-months and at 1 year
Measured: 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
Neurogenic Stress Cardiomyopathy and Stunned Myocardium (i.e. myocardial injury caused by sympathetic storm and autonomic dysregulation with hs-troponin elevation, left ventricular dysfunction or ECG changes)
Measured: follow-up of 1 year
Intracerebral pressure (ICP)
ICP level
Duration of therapy for ICP control/monitoring
Measured: during ICU stay up to 14 days after onset of aSAH symptoms
Intracerebral pressure (ICP)
Need for ICP therapies (hypothermia, decompressive craniotomy)
Measured: during ICU stay up to 14 days after onset of aSAH symptoms
Intracerebral pressure (ICP)
Duration of therapy for ICP control/monitoring
Measured: during ICU stay up to 14 days after onset of aSAH symptoms
Plasma catecholamine level
Plasma level of noradrenaline , adrenaline, and dopamine
Measured: within 3 hours of ICU arrival, at 24h, 48h and 72 h after onset of aSAH symptoms
Selected biomarkers
Selected biomarkers of brain injury: neurofilament light (NF-L), glial fibrillary acidic protein (GFAP), calcium binding protein S100B (S100B), ubiquitin carboxyterminal hydrolase L1 (UCH-L1), total tau, cytokines (tumour necrosis factor alpha, interleukins 6 and 10)
Measured: within 3 hours of ICU arrival and at 24h, at 48h and at 72h after onset of aSAH symptoms
Development of prognostication models
Development of prognostication models with a selected combination of brain imaging, clinical data, biomarkers and metabolomics by applying artificial intelligence and machine learning for long-term outcome after aSAH
Measured: long-term outcome at 3 months, at 1 and at 2 years after onset of aSAH symptoms
Development of prognostication models
Development of prognostication models with a selected combination of brain imaging, clinical data, biomarkers and metabolomics by applying artificial intelligence and machine learning for DCI after aSAH
Measured: between day 4 and 6 weeks after onset of aSAH symtoms
Development of prognostication models
Development of prognostication models with a selected combination of brain imaging, clinical data, biomarkers and metabolomics by applying artificial intelligence and machine learning for vasospasm after aSAH
Measured: within 21 days after onset of aSAH symptoms
Development of prognostication models
Development of prognostication models with a selected combination of brain imaging, clinical data, biomarkers and metabolomics by applying artificial intelligence and machine learning for EBI after aSAH
Measured: within 72 hours after onset of aSAH symtoms
Difference of MRI parameters between xenon and control group
Difference of MRI parameters (fractional anisotropy, axial diffucivity, radial diffucivity of diffusion tensor imaging, DTI) between xenon and control group and in predicting risk for EBI
Measured: within 72 hours after onset of aSAH symptoms
Difference of MRI parameters between xenon and control group
Difference of MRI parameters (fractional anisotropy, axial diffucivity, radial diffucivity of DTI) between xenon and control group and in predicting risk for vasospasm
Measured: within 21 days after onset of aSAH symptoms
Difference of MRI parameters between xenon and control group
Difference of MRI parameters (fractional anisotropy, axial diffucivity, radial diffucivity of DTI) between xenon and control group and in predicting risk for DCI
Measured: between day 4 and 6 weeks after onset of aSAH symptoms
Difference of MRI parameters between xenon and control group
Difference of MRI parameters (fractional anisotropy, axial diffucivity, radial diffucivity of DTI) between xenon and control group and in predicting risk for good/poor neurological outcome at 3 moths, at 1 year and at 2 years after onset of aSAH symptoms (mRS 0-2/mRS 3-6).
Measured: at 3 months, at 1 year and at 2 years after onset of aSAH symptoms
Difference of CTA findings
Difference of CTA ischemic findings between xenon and control group and in predicting risk for EBI
Measured: within 72 hours after onset of aSAH symptoms
Difference of CTA findings
Difference of ischemic findings in CTA between xenon and control group and in predicting risk for vasospasm
Measured: within 21 days after onset of aSAH symptoms
Difference of CTA findings
Difference of ischemic findings in CTA between xenon and control group and in predicting risk for DCI
Measured: between day 4 and 6 weeks after onset of aSAH symptoms
Difference of CTA findings between xenon and control group
Difference of ischemic findings in CTA between xenon and control group and in predicting risk for good/poor neurological outcome at 3 moths, at 1 year and at 2 years after onset of aSAH symptoms (mRS 0-2/mRS 3-6).
Measured: at 3 months, at 1 year and at 2 years after onset of aSAH symptoms
Difference of DSA findings between xenon and control group
Difference of DSA findings indicating ischemic pattern of perfusion between xenon and control group and in predicting risk for EBI
Measured: within 72 hours after onset of aSAH symptoms
Difference of DSA findings between xenon and control group
Difference of DSA findings indicating ischemic pattern of perfusion between xenon and control group and in predicting risk for vasospasm
Measured: within 21 days after onset of aSAH symptoms
Difference of DSA findings between xenon and control group
Difference of DSA findings indicating ischemic pattern of perfusion between xenon and control group and in predicting risk for DCI
Measured: between day 4 and 6 weeks after onset of aSAH symptoms
Difference of DSA findings between xenon and control group
Difference of DSA findings indicating ischemic pattern of perfusion between xenon and control group and in predicting risk for good/poor neurological outcome at 3 moths, at 1 year and at 2 years after onset of aSAH symptoms (mRS 0-2/mRS 3-6).
Measured: at 3 months, at 1 year and at 2 years after onset of aSAH symptoms
Activity of microglia cells assessed with PET
It will be explored whether [11C](R)-PK11195 can be used to test the hypothesis of neuroprotective effect of xenon and to explore the role of inflammatory process for DCI after SAH. This could be demonstrated by showing less microglial activation in xenon group than in the reference therapy group and in the patients with good outcome, i.e. no DCI; Difference of activity of microglia cells between xenon and control group and in predicting risk for DCI
Measured: DCI between day 4 and 6 weeks after onset of aSAH symptoms; The 1st PETscan 4 ±1 weeks after onset of aSAH symptoms and the 2nd scan at 3 months after onset of SAH symptoms.
Activity of microglia cells assessed with PET
It will be explored whether [11C](R)-PK11195 can be used to test the hypothesis of neuroprotective effect of xenon and to explore the role of inflammatory process for neurological outcome after SAH. This could be demonstrated by showing less microglial activation in xenon group than in the reference therapy group and in the patients with good outcome, i.e. mRS 0-2;
Measured: The 1st scan at 4 ±1 weeks after and the 2nd scan at 3 months after onset of SAH symptoms. Outcome: at 3 months, at 1 year and at 2 years after onset of aSAH symptoms
Cerebral fluid dynamics
Predictive value of CFD simulations assessed with 3 dimensional DSA within 4 days of ICU arrival in predicting risk for EBI within 72 hours after onset of aSAH symptoms
Measured: Measures performed within 72 hours of ICU arrival
Cerebral fluid dynamics
Predictive value of CFD simulations assessed with 3 dimensional DSA within 21 days of ICU arrival in predicting risk for neurological outcome at 3 months, at 1 year and at 2 years after SAH (mRS 0-2)
Measured: Measures performed within 21 days of ICU arrival; outcome at 3 months, at 1 year and at 2 years after onset of aSAH symptoms
Cerebral fluid dynamics
Predictive value of CFD simulations assessed with 3 dimensional DSA within 21 days of ICU arrival in predicting risk for DCI within 6 weeks after onset of aSAH symptoms
Measured: Measures performed within 21 days of ICU arrival; DCI within 6 weeks after onset of aSAH symptoms
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2021
- Study start22 Apr 2025
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Subarachnoid Hemorrhage, AneurysmalStudies of the same condition, open and under way.
- More trials run by Turku University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Study design is a single blind randomized two-armed parallel follow-up study.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Turku University Hospital
- Sponsor type
- Other government
- Collaborators
- Academy of Finland
- Responsible party
- Principal investigator, Timo Laitio, Turku University Hospital
- Investigators
- Timo T Laitio, MD, PhD, Principal investigator, Turku University Hospital and University of Turku, Turku , Finland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04696523
- Sponsor's protocol ID
- 109/2019 Xe-SAH
- Other IDs
- 2019-001542-17, 2019
- Acronym
- Xe-SAH
- Status last verified
- Apr 2025
- First submitted
- 2 Jan 2021
- Last updated
- 1 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data of this study will be available to investigators whose proposed use of the data has been approved by an independent review committee. Individual participant data that underlie the results reported in this Article will be shared (text, tables, figures, and appendices), after de-identification, along with the study protocol. These data will be available 6 months after the Article's pulication and will be available for 12 months from publication. Data can be used for individual participant data meta-analysis. Requests and proposals should be directed to timo.laitio@elisanet.fi. To gain access, data requestors will need to sign a data access agreement.
Publications
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.
PubMed 26978207Arola 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.
PubMed 29169472Laaksonen 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.
PubMed 37337295
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Xenon on Brain Injury, Neurological Outcome and Survival in Patients After Aneurysmal Subarachnoid Hemorrhage
- ClinicalTrials.gov ID
- NCT04696523
- Acronym / sponsor ID
- Xe-SAH / 109/2019 Xe-SAH
- Conditions
- Subarachnoid Hemorrhage, Aneurysmal, Cerebral Injury, Cerebral Ischemia, Cerebral Infarction, Cardiac Event, Cardiac Failure
- Keywords
- xenon, neuroprotection, aneurysmal subarachnoid hemorrhage
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Turku University HospitalOther government
- Collaborators
- Academy of Finland
- Study start
- 22 Apr 2025 (actual)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 6 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Assessments of efficacy:
- A brain Computer tomography angiography (CTA) and / or 3 D Digital subtraction angiography (DSA) (whenever possible instead of 2D DSA) will be performed at hospital arrival and whenever clinically indicated.
- 1st 3 Tesla MRI 72 ± 24 hours after onset of aSAH symptoms; 2nd 3 Tesla MRI 42 ± 4 days after onset of aSAH symptoms.
- 3D DSA: Computational fluid dynamic simulations (CFD), artificial intelligence and machine learning.
- Brain Positron emission tomography (PET): The 1st 4 ± 1 weeks and the 2nd at 3 months after onset of aSAH symptoms.
- Biochemical assessment: A blood samples of 20 ml for determination of plasma catecholamines, plasma metabolomics (see details of metabolomics in section 18.4.7), cardiac enzyme release (P-hs-troponin-T and heart fatty-acid binding protein), selected biomarkers will be analysed at intensive crae unit (ICU) arrival and at 24h, at 48h and at 72h after onset of SAH symptoms. In addition, a sample of spinal fluid will be collected through external ventricular drainage (EVD) at ICU arrival or as soon as it is in place and at 24h, at 48h and at 72h after onset of SAH symptoms for assessment of metabolomics
- Electrocardiograph (ECG) at ICU arrival and at 24h, at 48h and at 72h after onset of aSAH symptoms.
- Neurological evaluation: at 3, 12 and at 24 months after aSAH with GOSe, Modified ranking score (mRS).
Statistical methods: 1) Basic statistical tests (t-tests, Mann-Whitney, Chi square, etc); 2) Survival analysis methods; 3) An analysis of variance for repeated measurements; 4) A sample size of 100 is estimated on the basis of a recent studies in SAH patients to provide 80% power with a 2-sided α level of 0.05 to detect a mean difference of 0.02 (SD 0.035) in the global fractional anisotropy of white matter between the xenon group and the control group (98). Accordingly, this mean difference is estimated to have a predictive value for DCI and poor neurological outcome (i.e. mRS 3-6).Significance level of 0.05 and an estimation of 95 % confidence intervals will be used in the statistical analyses.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Study design is a single blind randomized two-armed parallel follow-up study.
| Arm | Type | Receives |
|---|---|---|
| Air/Oxygen | Active comparator | Drug: air/oxygenControl arm: air/oxygen with standard of care |
| xenon | Experimental | Drug: XenonXenon arm: xenon inhalation in air/oxygen with standard of care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- To be considered eligible to participate in this study, a SAH subject must meet the inclusion criteria listed below:
- 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
Key exclusion criteria (13 listed)
- An aSAH subject may not be enrolled in the trial if he/she meets any one of the exclusion criteria below:
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XenonXenon arm will be treated with xenon inhalation with endtidal concentration of 50 % in air/oxygen and with standard of care | Drug | xenon |
| air/oxygenControl group will be treated with air/oxygen | Drug | Air/Oxygen |
Primary outcome
Fractional anisotropy of the white matter
Time frame: 48-96 hours after start of aSAH symptoms
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.
30 secondary outcomes
Fractional anisotropy of white matter at cerebellum and/or at corpus callosum as assessed with the 1st MRI.
Time frame: 48-96 hours after start of aSAH symptoms
Safety and tolerability of xenon
Time frame: during the follow-up of one year
Composite of radiological early brain injury (EBI) and delayed cerebral ischemia (DCI)
Time frame: 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
Time frame: follow-up of 1 year
Intracerebral pressure (ICP)
Time frame: during ICU stay up to 14 days after onset of aSAH symptoms
Intracerebral pressure (ICP)
Time frame: during ICU stay up to 14 days after onset of aSAH symptoms
Intracerebral pressure (ICP)
Time frame: during ICU stay up to 14 days after onset of aSAH symptoms
Plasma catecholamine level
Time frame: within 3 hours of ICU arrival, at 24h, 48h and 72 h after onset of aSAH symptoms
Selected biomarkers
Time frame: within 3 hours of ICU arrival and at 24h, at 48h and at 72h after onset of aSAH symptoms
Development of prognostication models
Time frame: long-term outcome at 3 months, at 1 and at 2 years after onset of aSAH symptoms
Development of prognostication models
Time frame: between day 4 and 6 weeks after onset of aSAH symtoms
Development of prognostication models
Time frame: within 21 days after onset of aSAH symptoms
Development of prognostication models
Time frame: within 72 hours after onset of aSAH symtoms
Difference of MRI parameters between xenon and control group
Time frame: within 72 hours after onset of aSAH symptoms
Difference of MRI parameters between xenon and control group
Time frame: within 21 days after onset of aSAH symptoms
Difference of MRI parameters between xenon and control group
Time frame: between day 4 and 6 weeks after onset of aSAH symptoms
Difference of MRI parameters between xenon and control group
Time frame: at 3 months, at 1 year and at 2 years after onset of aSAH symptoms
Difference of CTA findings
Time frame: within 72 hours after onset of aSAH symptoms
Difference of CTA findings
Time frame: within 21 days after onset of aSAH symptoms
Difference of CTA findings
Time frame: between day 4 and 6 weeks after onset of aSAH symptoms
Difference of CTA findings between xenon and control group
Time frame: at 3 months, at 1 year and at 2 years after onset of aSAH symptoms
Difference of DSA findings between xenon and control group
Time frame: within 72 hours after onset of aSAH symptoms
Difference of DSA findings between xenon and control group
Time frame: within 21 days after onset of aSAH symptoms
Difference of DSA findings between xenon and control group
Time frame: between day 4 and 6 weeks after onset of aSAH symptoms
Difference of DSA findings between xenon and control group
Time frame: at 3 months, at 1 year and at 2 years after onset of aSAH symptoms
Activity of microglia cells assessed with PET
Time frame: DCI between day 4 and 6 weeks after onset of aSAH symptoms; The 1st PETscan 4 ±1 weeks after onset of aSAH symptoms and the 2nd scan at 3 months after onset of SAH symptoms.
Activity of microglia cells assessed with PET
Time frame: The 1st scan at 4 ±1 weeks after and the 2nd scan at 3 months after onset of SAH symptoms. Outcome: at 3 months, at 1 year and at 2 years after onset of aSAH symptoms
Cerebral fluid dynamics
Time frame: Measures performed within 72 hours of ICU arrival
Cerebral fluid dynamics
Time frame: Measures performed within 21 days of ICU arrival; outcome at 3 months, at 1 year and at 2 years after onset of aSAH symptoms
Cerebral fluid dynamics
Time frame: Measures performed within 21 days of ICU arrival; DCI within 6 weeks after onset of aSAH symptoms
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2025.
- Results publication: PubMed 26978207Laitio 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.
- Results publication: PubMed 29169472Arola 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.
- Derived from this study: PubMed 37337295Laaksonen 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.
- Individual participant dataSharing planned: Yes. The data of this study will be available to investigators whose proposed use of the data has been approved by an independent review committee. Individual participant data that underlie the results reported in this Article will be shared (text, tables, figures, and appendices), after de-identification, along with the study protocol. These data will be available 6 months after the Article's pulication and will be available for 12 months from publication. Data can be used for individual participant data meta-analysis. Requests and proposals should be directed to timo.laitio@elisanet.fi. To gain access, data requestors will need to sign a data access agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Timo T Laitio, MD, PhD principal investigator
Turku University Hospital and University of Turku, Turku , Finland
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Xenon and air/oxygen in people with Subarachnoid Hemorrhage, Aneurysmal and Cerebral Injury, run by Turku University Hospital at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Finland, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Timo T Laitio, MD, PhD (+358504653201, timo.laitio@tyks.fi), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fractional anisotropy of the white matter (time frame: 48-96 hours after start of aSAH symptoms). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04696523, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2025.