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Sevoflurane- Safety in Long-term Sedation Procedures

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ClinicalTrials.gov Identifier: NCT01802255
Recruitment Status : Recruiting
First Posted : March 1, 2013
Last Update Posted : March 24, 2017
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Poisoning by Inhaled Anaesthetic Fluoride Poisoning Recovery From Sedation Renal Function Hepatic Function Drug: Sevoflurane Drug: Midazolam Phase 3

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Study of the Safety of Administration of Sevoflurane for Long-term Critically Ill Patients Sedation Undergoing Mechanical Ventilation. Prospective, Controlled, Randomized, Multicenter, Clinical Trial.
Study Start Date : March 2013
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Inhalatory sedation
Sevoflurane given via AnaConDa for sedation minimum 48 hours
Drug: Sevoflurane
Sedation with inhaled anesthetic via AnaConDa.
Other Name: Sevorane, Ultane, Sojourn
Active Comparator: Intravenous sedation
Midazolam given intravenously for sedation minimum 48 hours
Drug: Midazolam
Intravenous sedation.
Other Name: Versed

Outcome Measures

Primary Outcome Measures :
  1. Maintenance of renal function. [ Time Frame: Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week ]
    Measurements in plasma: creatinine and cystatin levels.

Secondary Outcome Measures :
  1. Assessment of liver function [ Time Frame: Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week ]
    Measurements in plasma: SGOT (aspartate aminotransferase, AST), SGPT (alanine aminotransferase, ALT), LDH (lactate dehydrogenase) alkaline phosphatase, conjugated and total bilirubin, cholesterol, triglycerides, albumin, total proteins, electrolytes and glycogen.

  2. Plasma pharmacokinetics of fluoride [ Time Frame: Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week ]
    Determine evolutionary plasmatic levels of fluorides.

  3. Incidence of delirium [ Time Frame: Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week ]
    The incidence of delirium will be evaluated by the CAM-ICU method.

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

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

Exclusion Criteria:

  • 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
Contacts and Locations

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): NCT01802255

Contact: F Javier Belda, MD, PhD fjbelda@uv.es

Hospital Clínico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Contact: F Javier Belda, MD, PhD         
Sponsors and Collaborators
F Javier Belda
Study Director: Marina Soro, MD, PhD Hospital Clínico Universitario de Valencia
Principal Investigator: 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
More Information

Responsible Party: F Javier Belda, Prof. Dr. F Javier Belda, Fundacion para la Investigacion del Hospital Clinico Universitario de Valencia
ClinicalTrials.gov Identifier: NCT01802255     History of Changes
Other Study ID Numbers: ECSEVO-LT-011
2011-002555-34 ( EudraCT Number )
First Posted: March 1, 2013    Key Record Dates
Last Update Posted: March 24, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Shared data will be anonymous

Keywords provided by F Javier Belda, Fundacion para la Investigacion del Hospital Clinico Universitario de Valencia:
Inhalatory sedation

Additional relevant MeSH terms:
Fluoride Poisoning
Chemically-Induced Disorders
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Anesthetics, Inhalation