Sevoflurane- Safety in Long-term Sedation Procedures

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Fundación para la Investigación del Hospital Clínico de Valencia
Sponsor:
Information provided by (Responsible Party):
F Javier Belda, Fundacion para la Investigacion del Hospital Clinico Universitario de Valencia
ClinicalTrials.gov Identifier:
NCT01802255
First received: February 9, 2013
Last updated: April 4, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Poisoning by Inhaled Anaesthetic
Fluoride Poisoning
Recovery From Sedation
Renal Function
Hepatic Function
Drug: Sevoflurane
Drug: Midazolam
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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.

Resource links provided by NLM:


Further study details as provided by Fundación para la Investigación del Hospital Clínico de Valencia:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Measurements in plasma: creatinine and cystatin levels.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    Determine evolutionary plasmatic levels of fluorides.

  • 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 ] [ Designated as safety issue: No ]
    The incidence of delirium will be evaluated by the CAM-ICU method.


Estimated Enrollment: 50
Study Start Date: March 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Inhalatory sedation
Sevoflurane given via AnaConDa for sedation minimum 48 hours
Drug: Sevoflurane
Treatment group: Inhalatory sedation with sevoflurane via AnaConDa.
Active Comparator: Intravenous sedation
Midazolam given intravenously for sedation minimum 48 hours
Drug: Midazolam
Control Group: Intravenous sedation with midazolam.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01802255

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

Locations
Spain
Hospital Clínico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Contact: F Javier Belda, MD, PhD         
Sponsors and Collaborators
F Javier Belda
Investigators
Study Director: Marina Soro, MD, PhD University of 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

Publications:
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
Study First Received: February 9, 2013
Last Updated: April 4, 2013
Health Authority: Spain: Comité Ético de Investigación Clínica
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Fundación para la Investigación del Hospital Clínico de Valencia:
Inhalatory sedation
Sevoflurane
AnaConDa
Nephrotoxicity
Hepatotoxicity
Midazolam
Propofol

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

ClinicalTrials.gov processed this record on August 19, 2014