search
Back to results

Sevoflurane in Subarachnoidal Haemorrhage (Sevoflurane)

Primary Purpose

Subarachnoid Haemorrhage (SAH)

Status
Withdrawn
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
Sevoflurane
Propofol
Midazolam
MIRUS™System
Sponsored by
University of Zurich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Subarachnoid Haemorrhage (SAH) focused on measuring severe SAH, prevention of vasospasm and/ or brain oedema, Sevoflurane, Postconditioning

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Hospital Zurich

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Other

Arm Label

Sevoflurane

Propofol or Midazolam

MIRUS™System

Arm Description

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.

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.)

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.

Outcomes

Primary Outcome Measures

Feasibility: Incidence of concerns/problems in the use of sevoflurane by intensivist and ICU nurse at the stopping of sevoflurane postconditioning.
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

Quality of sedation
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
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.

Full Information

First Posted
October 7, 2016
Last Updated
May 28, 2020
Sponsor
University of Zurich
search

1. Study Identification

Unique Protocol Identification Number
NCT02946437
Brief Title
Sevoflurane in Subarachnoidal Haemorrhage
Acronym
Sevoflurane
Official Title
Short Term Application of Sevoflurane in Patients With Subarachnoid Haemorrhage: a Feasibility and Safety Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Patients failed to be enrolled because of tight exclusion criteria.
Study Start Date
November 1, 2015 (Actual)
Primary Completion Date
December 31, 2019 (Actual)
Study Completion Date
December 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Zurich

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Subarachnoid Haemorrhage (SAH)
Keywords
severe SAH, prevention of vasospasm and/ or brain oedema, Sevoflurane, Postconditioning

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sevoflurane
Arm Type
Experimental
Arm Description
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.
Arm Title
Propofol or Midazolam
Arm Type
Active Comparator
Arm Description
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.)
Arm Title
MIRUS™System
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Sevoflurane
Other Intervention Name(s)
Sevorane®
Intervention Description
Postconditioning with sevoflurane (0.5-1.5vol%) for 4 hours after coiling or clipping of cerebral aneurysm in patients with severe SAH
Intervention Type
Drug
Intervention Name(s)
Propofol
Other Intervention Name(s)
Disoprivan®
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Midazolam
Other Intervention Name(s)
Dormicum®
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
MIRUS™System
Intervention Description
The MIRUS™System is the normally used standard equipment for the administration of volatile anaesthetics to patients.
Primary Outcome Measure Information:
Title
Feasibility: Incidence of concerns/problems in the use of sevoflurane by intensivist and ICU nurse at the stopping of sevoflurane postconditioning.
Description
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
Time Frame
4 hours
Secondary Outcome Measure Information:
Title
Quality of sedation
Description
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)
Time Frame
5 hours
Title
Neuroprotective effects
Description
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.
Time Frame
14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emanuela Keller, MD Prof.
Organizational Affiliation
University of Zurich
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Zurich
City
Zurich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Sevoflurane in Subarachnoidal Haemorrhage

We'll reach out to this number within 24 hrs