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Sevoflurane in Subarachnoidal Haemorrhage (Sevoflurane)

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ClinicalTrials.gov Identifier: NCT02946437
Recruitment Status : Recruiting
First Posted : October 27, 2016
Last Update Posted : April 6, 2018
Sponsor:
Information provided by (Responsible Party):
Emanuela Keller, University of Zurich

Brief Summary:
Feasibility and safety of short term application of sevoflurane in patients with SAH treated with aneurysm coiling or clipping in the setting of a neurointensive care unit.

Condition or disease Intervention/treatment Phase
Subarachnoid Haemorrhage (SAH) Drug: Sevoflurane Drug: Propofol Drug: Midazolam Device: MIRUS™System Phase 2

Detailed Description:
After admission to the ICU, before the coiling / clipping intervention has been performed, the patients are screened for eligibility. When the patients are coming back to the ICU, after successful aneurysm coiling or clipping, data of artificial ventilation, systemic and other cerebral parameters will be collected continuously by online monitoring, starting at baseline and stopping at discharge of the ICU. Sevoflurane will be vaporized and administrated by the MIRUS™System directly to the inspiratory part of the ventilation circuit for the next 4 hours. In the following 14 days of the stay on the ICU, standard monitoring parameters, the appearance of vasospasm and brain oedema will be recorded. Besides the continuous online monitoring, laboratory assessment will be performed daily. At day 7±2 and day 14±2 after bleeding a MRI or CT examination will be performed, according to the clinical condition of the patient, to detect secondary brain injuries, as ischemia or brain oedema. At ICU discharge, the neurological outcome will be assesses applying GOS.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Short Term Application of Sevoflurane in Patients With Subarachnoid Haemorrhage: a Feasibility and Safety Study
Study Start Date : August 2015
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : March 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arm Intervention/treatment
Experimental: Sevoflurane

Sevoflurane postconditioning will start after the bleeding source is excluded by coiling or clipping as soon as the patient returns to the ICU and will be continued for 4 hours. 0.5-1.5vol% sevoflurane will be administrated into the ventilation circuit by a MIRUS™System.

The used dose (0.5-1.5vol%) is a lower dose as used for anaesthesia for a surgical intervention (0.5-3vol%), but high enough to provide sufficient sedation.

Drug: Sevoflurane
Postconditioning with sevoflurane (0.5-1.5vol%) for 4 hours after coiling or clipping of cerebral aneurysm in patients with severe SAH
Other Name: Sevorane®

Device: MIRUS™System
The MIRUS™System is the normally used standard equipment for the administration of volatile anaesthetics to patients.

Active Comparator: Propofol or Midazolam
Propofol or midazolam will be administrated intravenously before and after the postconditioning with sevoflurane as in the standard sedation regimen of the Neurointensive Care Unit, University Hospital Zurich (propofol 0.3-4.0mg/kg/h cont. i.v.; midazolam 0.03-0.2mg/kg/h cont. i.v.)
Drug: Propofol
Before and after postconditioning with sevoflurane the patients will be sedated with intravenous sedatives (midazolam or propofol). The quality of sedation before the postconditioning (propofol or midazolam) will be compared to the sedation one hour after starting the postconditioning (sevoflurane) in the same patient.
Other Name: Disoprivan®

Drug: Midazolam
Before and after postconditioning with sevoflurane the patients will be sedated with intravenous sedatives (midazolam or propofol). The quality of sedation before the postconditioning (propofol or midazolam) will be compared to the sedation one hour after starting the postconditioning (sevoflurane) in the same patient.
Other Name: Dormicum®

MIRUS™System
MIRUS™ is a newly developed device, considered as vaporizer system, which can be used in the setting of operating rooms or in intensive care units. The MIRUS™System is successfully in use in daily clinical practice. This type of device is similar to the well-known AnaConDa® system (AnaConDa®, Sedana Medical, Uppsala, S) with several advantages. Since 2005 the anaesthetic-conserving device AnaConDa® facilitates, from a technical viewpoint, the routine use of volatile anaesthetics in intensive care patients as part of prolonged sedation, using ICU ventilators (Soukup J et al., 2009). The MIRUS™System forms a closed loop. It measures the end-tidal concentration of the anaesthetic gas and governs the application of the anaesthetic gas according to these values and the ventilation parameters.
Drug: Sevoflurane
Postconditioning with sevoflurane (0.5-1.5vol%) for 4 hours after coiling or clipping of cerebral aneurysm in patients with severe SAH
Other Name: Sevorane®

Device: MIRUS™System
The MIRUS™System is the normally used standard equipment for the administration of volatile anaesthetics to patients.




Primary Outcome Measures :
  1. Feasibility: Incidence of concerns/problems in the use of sevoflurane by intensivist and ICU nurse at the stopping of sevoflurane postconditioning. [ Time Frame: 4 hours ]
    • Incidence of concerns of users in relation to the application of standard sedation with propofol or midazolam
    • Incidence of complications with sevoflurane preparation, sevoflurane application, MIRUS™-installation, MIRUS™-function, MIRUS™-removal
    • User friendliness compared to settings for artificial ventilation supplemented with NO


Secondary Outcome Measures :
  1. Quality of sedation [ Time Frame: 5 hours ]
    • Incidence of insufficient sedation during postconditioning with sevoflurane, measured with:

      • Ramsay Sedation Scale (RSS <2)
      • Richmond Agitation-Sedation Scale (RASS >0)
      • Bispectral index (BIS >30)
      • Incidence of use of additional sedative medication as midazolam, propofol
    • in relation to the sedation regimen before and after the postconditioning (dose and use of additional sedative medication as midazolam, propofol)

  2. Neuroprotective effects [ Time Frame: 14 days ]
    • Number of days during the 14 days monitoring period with signs of DIND

      • incidence of new neurological deficits on daily clinical visits
      • incidence of 2 consecutive metabolic crisis identified by microdialysis, defined as lactate/pyrovate-ratio (L/P-ratio) >40
      • incidence of PtiO2 <20mmHg at least 60 minutes- immediately before the measurement
      • incidence of new perfusion deficits in perfusion-CT and/ or -MRI, new infarctions in contrast enhanced CT/ MRI
    • Neurological outcome (GOS) will be assessed at ICU discharge and compared to data from the literature.



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients of either sex aged 18-85 years
  • Patients with severe aneurysmal SAH, Hunt/Hess 3 to 5.
  • The ruptured aneurysm is successfully excluded with coiling or clipping
  • Sedation and mechanical ventilation necessary due to the clinical situation
  • ICP monitoring in use due to the clinical situation
  • ICP < 20mmHg without medical treatment
  • Systolic blood pressure values (BP syst) > 120 mmHg with no need for catecholamines
  • Female patients of childbearing potential with negative pre-treatment serum pregnancy test
  • Informed consent obtained

Exclusion Criteria:

  • Significant kidney disease, defined as plasma creatinine >120 µmol/l
  • Significant liver disease, defined as Aspartate-Aminotransferase (AST) >200 U/l
  • Significant elongation of the QTc interval: female < 470 msec/ male < 450 msec; based on 'Bazett's Formula'
  • History of epilepsia and/ or occurring seizures with aneurysm rupture
  • Pneumocephalus after surgery excluded by CT scan performed immediately after clipping
  • History of allergic disorders
  • History for, or relatives with a history for malignant hyperthermia
  • History or signs for neuromuscular disease
  • Pre-existing disability
  • Patients participating in an interventional clinical trial within the last 30 days before start of treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02946437


Contacts
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Contact: Emanuela Keller, MD Prof +41-44-255 56 71 emanuela.keller@usz.ch
Contact: Carl Izumi Muroi, MD +41-44-255-56-24 carl.muroi@usz.ch

Locations
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Switzerland
University Hospital Zurich Recruiting
Zurich, Switzerland, 8091
Contact: Emanuela Keller, MD Prof.    +41 44 255 56 71    emanuela.keller@usz.ch   
Sponsors and Collaborators
University of Zurich
Investigators
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Principal Investigator: Emanuela Keller, MD Prof. University of Zurich

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Responsible Party: Emanuela Keller, Prof. Dr. med., University of Zurich
ClinicalTrials.gov Identifier: NCT02946437     History of Changes
Other Study ID Numbers: 2014-0397
2015DR2134 ( Other Identifier: Swissmedic )
First Posted: October 27, 2016    Key Record Dates
Last Update Posted: April 6, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Emanuela Keller, University of Zurich:
severe SAH
prevention of vasospasm and/ or brain oedema
Sevoflurane
Postconditioning

Additional relevant MeSH terms:
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Brain Diseases
Hemorrhage
Subarachnoid Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Propofol
Midazolam
Sevoflurane
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Adjuvants, Anesthesia
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Anesthetics, Inhalation