Sevoflurane- Safety in Long-term Sedation Procedures

NCT01802255 | Withdrawn Phase 3 DMC

• 2 other identifiers: ECSEVO-LT-0112011-002555-34
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Patients needing intensive care often require sedative drugs to reduce anxiety and agitation during ventilator care and invasive therapeutic and diagnostic procedures. At present there is no optimal sedative agent for these patients. The most commonly used sedative agents in intensive care units are midazolam and propofol. Both drugs have side effects of clinical importance. At present, a viable alternative to intravenous sedation is inhalatory sedation. Sevoflurane, as other inhaled anesthetic agents, is sedative in low doses. A new simplified method of administration of isoflurane or sevoflurane has been developed. The Anesthetic Conserving Device is a modified heat-moisture exchanger (HME) that permits direct infusion of sevoflurane to the airway, where it is vaporized in an evaporator rod in the device. However, the use of sevoflurane is limited to anesthesia and sedation lasting no more than 12 hours, since the possible renal problems posed by inorganic fluoride in prolonged operations remain the subject of controversy. The primary aim (and primary hypothesis) of the current trial is to determine whether sevoflurane can be administered as a sedative drug for more than 48 hours without clinically relevant physiopathological effects on kidney and liver function. Other end-points of the trial are to evaluate the quality of sedation of sevoflurane, in terms of sedation control, the rapidity and predictability of awakening, and the incidence of delirium in critical care patients.

Conditions

Poisoning by Inhaled Anaesthetic; Fluoride Poisoning; Recovery From Sedation; Renal Function; Hepatic Function

Keywords

Inhalatory sedation; Sevoflurane; AnaConDa; Nephrotoxicity; Hepatotoxicity; Midazolam; Propofol

Outcome Measures

Primary Outcomes (1)

• Maintenance of renal function.

  Measurements in plasma: creatinine and cystatin levels.

  Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week

Secondary Outcomes (3)

• Assessment of liver function

  Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week

• Plasma pharmacokinetics of fluoride

  Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week

• Incidence of delirium

  Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week

Study Arms (2)

Inhalatory sedation

EXPERIMENTAL

Sevoflurane given via AnaConDa for sedation minimum 48 hours

Drug: Sevoflurane

Intravenous sedation

ACTIVE COMPARATOR

Midazolam given intravenously for sedation minimum 48 hours

Drug: Midazolam

Interventions

Sevoflurane DRUG

Sedation with inhaled anesthetic via AnaConDa.

Also known as: Sevorane, Ultane, Sojourn

Inhalatory sedation

Midazolam DRUG

Intravenous sedation.

Also known as: Versed

Intravenous sedation

Eligibility Criteria

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

You may qualify if:

• Signing of the informed consent document (patient or relatives).
• Patient age 18 years or older.
• Expected minimum duration of sedation: 48 hours.

You may not qualify if:

• Chronic renal failure treated with replacement therapy (hemodialysis or peritoneal dialysis).
• Acute kidney injury in Stage 3 of AKIN classification
• Grade C hepatic Child-Pugh classification
• Established Acute Respiratory Distress Syndrome (ARDS).
• Central nervous system pathology with cognitive disorders that not allow performing the test of the study: severe dementia, Alzheimer's disease, depression, schizophrenia, acute stroke.
• Head trauma with Glasgow \<12.
• Patient treated with antiepileptic drugs that must be maintained during the study period
• Patients requiring the use of neuromuscular blocking agents during the infusion of study drug, except for the insertion of the endotracheal tube.
• Epidural or spinal analgesia
• Allergy or known hypersensitivity to any of the study drugs
• Patients with known or suspected genetic susceptibility to malignant hyperthermia
• Previous participation in this trial
• Participation in another clinical trial within 4 weeks prior to selection.
• Pregnant women

Sponsors & Collaborators

• F Javier Belda: lead

Study Sites (1)

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Related Publications (2)

• Kong KL, Bion JF. Sedating patients undergoing mechanical ventilation in the intensive care unit--winds of change? Br J Anaesth. 2003 Mar;90(3):267-9. doi: 10.1093/bja/aeg066. No abstract available.

  PMID: 12594134 BACKGROUND

• Rohm KD, Wolf MW, Schollhorn T, Schellhaass A, Boldt J, Piper SN. Short-term sevoflurane sedation using the Anaesthetic Conserving Device after cardiothoracic surgery. Intensive Care Med. 2008 Sep;34(9):1683-9. doi: 10.1007/s00134-008-1157-x. Epub 2008 May 24.

  PMID: 18500419 BACKGROUND

MeSH Terms

Conditions

Fluoride Poisoning

Interventions

Sevoflurane; Midazolam

Condition Hierarchy (Ancestors)

Poisoning; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Methyl Ethers; Ethers; Organic Chemicals; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Marina Soro, MD, PhD

  Hospital Clínico Universitario de Valencia

  STUDY DIRECTOR

• Luciano Aguilera, MD, PhD

  Hospital de Basurto

  PRINCIPAL INVESTIGATOR

• Carlos Soria, MD, PhD

  Complejo Asistencial de León

  PRINCIPAL INVESTIGATOR

• Francisco Acosta, MD, PhD

  Hospital Universitario Virgen de la Arrixaca

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. F Javier Belda

Study Record Dates

• First Submitted: February 9, 2013
• First Posted: March 1, 2013
• Study Start: March 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: June 1, 2015
• Last Updated: August 24, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share

Locations

ES (1)