Effect of Xenon on Brain Injury After Aneurysmal Subarachnoid Hemorrhage — Xe-SAH  

Cerebral Infarction Clinical Trial

Official title: Effect of Xenon on Brain Injury, Neurological Outcome and Survival in Patients After Aneurysmal Subarachnoid Hemorrhage

Status Not yet recruiting

Clinical 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). 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.

Clinical Trial Description

Assessments of efficacy:

1. 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.

2. 1st 3 Tesla MRI 72 ± 24 hours after onset of aSAH symptoms; 2nd 3 Tesla MRI 42 ± 4 days after onset of aSAH symptoms.

3. 3D DSA: Computational fluid dynamic simulations (CFD), artificial intelligence and machine learning.

4. Brain Positron emission tomography (PET): The 1st 4 ± 1 weeks and the 2nd at 3 months after onset of aSAH symptoms.

5. 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

6. Electrocardiograph (ECG) at ICU arrival and at 24h, at 48h and at 72h after onset of aSAH symptoms.

7. 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. ;

Related Conditions & MeSH terms

• Brain Injuries
• Brain Ischemia
• Cardiac Event
• Cardiac Failure
• Cerebral Infarction
• Cerebral Injury
• Cerebral Ischemia
• Heart Failure
• Hemorrhage
• Infarction
• Ischemia
• Subarachnoid Hemorrhage
• Subarachnoid Hemorrhage, Aneurysmal
• Wounds and Injuries

• NCT number: NCT04696523
• Study type: Interventional
• Source: Turku University Hospital
• Contact: Timo T Laitio, MD, PhD
• Phone: +358504653201
• Email: timo.laitio@tyks.fi
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: October 1, 2023
• Completion date: December 31, 2027