Clinical trial NCT02166853: Effects of SEvoflurane on Gas Exchange and Inflammation in Patients With ARDS (SEGA Study)
Official title: Effect of Early 48-hour Sevoflurane Inhalation on Gas Exchange and Inflammation in Patients Presenting With Acute Respiratory Distress Syndrome (ARDS) : a Monocentric, Prospective, Randomized Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Respiratory Distress Syndrome
Keywords: Acute respiratory distress syndrome (ARDS)
Sevoflurane
Mechanical ventilation
Intensive Care Unit (ICU)
Prospective study
Lung injury
Gas exchange
Inflammation
Receptor for advanced glycation end-produts (RAGE)
sRAGE
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2014-06-18
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Numerous trials support the efficacy and safety of volatile anesthetic agents, namely inhalation of sevoflurane through dedicated devices, for the sedation of ICU patients. Several preclinical studies have shown that sevoflurane inhalation improves gas exchange and decreases pulmonary and systemic inflammation in experimental models of acute respiratory distress syndrome (ARDS).

The purpose of our prospective monocentric, randomized, controlled trial is to evaluate the effects of an early 48-hour sevoflurane inhalation on gas exchange and inflammation in patients with ARDS.

Detailed description: BACKGROUND:

Acute respiratory distress syndrome (ARDS) is characterized by hypoxemic respiratory failure that can be lethal in 30 to 60% of patients. Its pathophysiological landmark, diffuse alveolar damage, is associated with alveolar inflammation, epithelial injury and alveolar fluid clairance impairment.

Several preclinical studies have shown that early sevoflurane inhalation improves gas exchange, reduces alveolar edema and attenuates pulmonary and systemic inflammation in experimental models of ARDS.

To date, no clinical trial has assessed the effects of early sevoflurane inhalation in ARDS patients.

DESIGN NARRATIVE:

The purpose of this prospective, randomized, controlled study is to evaluate the effects of a 48-hour sevoflurane inhalation strategy on gas exchange and both systemic and pulmonary inflammation in the early phase of ARDS.

After inclusion, ICU patients with moderate to severe ARDS (according to the Berlin definition of ARDS criteria; JAMA 2010) will be randomized into two groups :

* a "conventional group", in which intravenous sedation with midazolam will be administered
* a "sevoflurane group", in which patients will inhale sevoflurane during a 48 hour-period, through dedicated devices Arterial blood gases will be analyze before randomization and at 24, 48, 72, 96, and 120 hours.

Bronchoalveolar lavages (BAL) and blood samples will be assessed before randomization and at 48 hours, in order to measure tumor necrosis factor-alpha (TNFα), interleukin (IL)-1β, IL-6, IL-8 and sRAGE levels. Duplicate assays will be performed with Multiplex (TNFα/interleukins) or ELISA (sRAGE).

During the 48-hour treatment period, bispectral index (BIS®) values ranging from 40 to 50 will be targeted and neuromuscular blocking agents (cisatracurium) will be administered in both groups. Protective ventilation strategies will be applied, as well as other guidelines or recommendations on the management of ICU patients with ARDS.

Eligibility criteria: Inclusion Criteria:

* Patients with criteria for moderate to severe ARDS since less than 24 hours (
* Informed consent

Exclusion Criteria:

* Suspected or proven intracranial hypertension
* Midazolam, sevoflurane or cisatracurium allergy
* Medical history of malignant hyperthermia
* Severe liver failure
* Chemotherapy treatment in the last month
* Severe neutropenia (\< 0.5 G/l)

Primary outcomes:
measure: PaO2/FiO2 ratio
timeFrame: at 48 hours
Secondary outcomes:
measure: - Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8
timeFrame: at 48 hours
measure: Plasma and alveolar levels of sRAGE
timeFrame: at 48 hours
measure: PaO2/FiO2 ratio
timeFrame: at day 1, day 3, day 5
measure: Lowest PaO2/FiO2 during the first 5 days of the study
timeFrame: at 5 days
measure: Mean PaO2/FiO2 ratio during the first 5 days of the study
timeFrame: at 5 days
measure: Pulmonary static compliance, resistance and elastance
timeFrame: at day 1, day 2
measure: Duration of controlled mechanical ventilation
timeFrame: at day 30
measure: Total duration of mechanical ventilation (controlled/assisted)
timeFrame: at day 30
measure: Number of ventilatory-free days
timeFrame: at day 30
measure: Number of organ failure-free days
timeFrame: at day 30
measure: Vasopressor requirements
timeFrame: at 48 hours
measure: Mortality
timeFrame: at day 30
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Matthieu JABAUDON
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jabaudon M, Boucher P, Imhoff E, Chabanne R, Faure JS, Roszyk L, Thibault S, Blondonnet R, Clairefond G, Guerin R, Perbet S, Cayot S, Godet T, Pereira B, Sapin V, Bazin JE, Futier E, Constantin JM. Sevoflurane for Sedation in Acute Respiratory Distress Syndrome. A Randomized Controlled Pilot Study. Am J Respir Crit Care Med. 2017 Mar 15;195(6):792-800. doi: 10.1164/rccm.201604-0686OC.