Sevoflurane in Subarachnoidal Haemorrhage

NCT02946437 | Withdrawn Phase 2

• 2 other identifiers: 2014-03972015DR2134
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Subarachnoid Haemorrhage (SAH)

Keywords

severe SAH; prevention of vasospasm and/ or brain oedema; Sevoflurane; Postconditioning

Outcome Measures

Primary Outcomes (1)

• 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

  4 hours

Secondary Outcomes (2)

• Quality of sedation

  5 hours

• Neuroprotective effects

  14 days

Study Arms (3)

Sevoflurane

EXPERIMENTAL

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; Device: MIRUS™System

Propofol or Midazolam

ACTIVE COMPARATOR

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; Drug: Midazolam

MIRUS™System

OTHER

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; Device: MIRUS™System

Interventions

Sevoflurane DRUG

Postconditioning with sevoflurane (0.5-1.5vol%) for 4 hours after coiling or clipping of cerebral aneurysm in patients with severe SAH

Also known as: Sevorane®

MIRUS™System; Sevoflurane

Propofol DRUG

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.

Also known as: Disoprivan®

Propofol or Midazolam

Midazolam DRUG

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.

Also known as: Dormicum®

Propofol or Midazolam

MIRUS™System DEVICE

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

MIRUS™System; Sevoflurane

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (1)

University Hospital Zurich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Brain Edema

Interventions

Sevoflurane; Propofol; Midazolam

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Methyl Ethers; Ethers; Organic Chemicals; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Emanuela Keller, MD Prof.

  University of Zurich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: October 7, 2016
• First Posted: October 27, 2016
• Study Start: November 1, 2015
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: June 2, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)