Effects of SEvoflurane on Gas Exchange and Inflammation in Patients With ARDS (SEGA Study)

NCT ID: NCT02166853

Last Updated: 2016-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2016-03-31

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.

Conditions

Acute Respiratory Distress Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

conventional group

a "conventional group", in which intravenous sedation with midazolam will be administered

Group Type: EXPERIMENTAL

midazolam

Intervention Type: DRUG

Sedation with intravenous midazolam

sevoflurane group

a "sevoflurane group", in which patients will inhale sevoflurane during a 48 hour-period, through dedicated devices

Group Type: EXPERIMENTAL

sevoflurane

Intervention Type: DRUG

Sedation with inhaled sevoflurane

Interventions

sevoflurane

Sedation with inhaled sevoflurane

Intervention Type: DRUG

midazolam

Sedation with intravenous midazolam

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Clermont-Ferrand

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthieu JABAUDON

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Clermont-Ferrand

Locations

CHU Clermont-Ferrand

Clermont-Ferrand, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 27611637 (View on PubMed)

Other Identifiers

2013-005389-21

Identifier Type: -

Identifier Source: secondary_id

CHU-0195

Identifier Type: -

Identifier Source: org_study_id