Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Sevoflurane in Subarachnoidal Haemorrhage (Sevoflurane)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02946437
Recruitment Status : Withdrawn (Patients failed to be enrolled because of tight exclusion criteria.)
First Posted : October 27, 2016
Last Update Posted : June 2, 2020
Sponsor:
Information provided by (Responsible Party):
Emanuela Keller, University of Zurich

Tracking Information
First Submitted Date  ICMJE October 7, 2016
First Posted Date  ICMJE October 27, 2016
Last Update Posted Date June 2, 2020
Actual Study Start Date  ICMJE November 1, 2015
Actual Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 24, 2016)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2018)
  • 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)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2016)
  • 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)
  • 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 CBF < 25ml/100g/min measured with NIRS ICG dye dilution
      • data of continuous NIRS oximetry (aHboxy, aHbdeoxy, aHbtotal, SbtO2)
      • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sevoflurane in Subarachnoidal Haemorrhage
Official Title  ICMJE Short Term Application of Sevoflurane in Patients With Subarachnoid Haemorrhage: a Feasibility and Safety Study
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Subarachnoid Haemorrhage (SAH)
Intervention  ICMJE
  • 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®
  • 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®
  • Device: MIRUS™System
    The MIRUS™System is the normally used standard equipment for the administration of volatile anaesthetics to patients.
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: Sevoflurane
    • Device: MIRUS™System
  • 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.)
    Interventions:
    • Drug: Propofol
    • Drug: Midazolam
  • 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.
    Interventions:
    • Drug: Sevoflurane
    • Device: MIRUS™System
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: May 28, 2020)
0
Original Estimated Enrollment  ICMJE
 (submitted: October 24, 2016)
10
Actual Study Completion Date  ICMJE December 31, 2019
Actual Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02946437
Other Study ID Numbers  ICMJE 2014-0397
2015DR2134 ( Other Identifier: Swissmedic )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Emanuela Keller, University of Zurich
Study Sponsor  ICMJE University of Zurich
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Emanuela Keller, MD Prof. University of Zurich
PRS Account University of Zurich
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP