Clinical trial NCT01802255: Sevoflurane- Safety in Long-term Sedation Procedures
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 type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Poisoning by Inhaled Anaesthetic
Fluoride Poisoning
Recovery From Sedation
Renal Function
Hepatic Function
Keywords: Inhalatory sedation
Sevoflurane
AnaConDa
Nephrotoxicity
Hepatotoxicity
Midazolam
Propofol
Lead sponsor: Fundación para la Investigación del Hospital Clínico de Valencia
Sponsor class: OTHER
First posted: 2013-03-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility 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

Primary outcomes:
measure: Maintenance of renal function.
timeFrame: Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week
Secondary outcomes:
measure: Assessment of liver function
timeFrame: Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week
measure: Plasma pharmacokinetics of fluoride
timeFrame: Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week
measure: Incidence of delirium
timeFrame: Baseline. Posteriorly, every 12 hours for the full length of sedation. After sedation, every 24 hours up to one week
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
affiliation: Hospital Clínico Universitario de Valencia
name: Marina Soro, MD, PhD
role: STUDY_DIRECTOR
affiliation: Hospital de Basurto
name: Luciano Aguilera, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Complejo Asistencial de León
name: Carlos Soria, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Virgen de la Arrixaca
name: Francisco Acosta, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.