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

Acute Respiratory Distress Syndrome Clinical Trial

— SEGA  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02166853
• Other study ID #: CHU-0195
• Secondary ID: 2013-005389-21
• Status: Completed
• Phase: Phase 4
• First received: June 16, 2014
• Last updated: March 3, 2016
• Start date: April 2014
• Est. completion date: March 2016

Study information

• Verified date: March 2016
• Source: University Hospital, Clermont-Ferrand
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: March 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 99 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Inflammation
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

Drug:
• sevoflurane
Sedation with inhaled sevoflurane
• midazolam
Sedation with intravenous midazolam

Locations

Country	Name	City	State
France	CHU Clermont-Ferrand	Clermont-Ferrand

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PaO2/FiO2 ratio		at 48 hours	No
Secondary	- Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFa, interleukin (IL)-1ß, IL-6, IL-8		at 48 hours	No
Secondary	Plasma and alveolar levels of sRAGE		at 48 hours	No
Secondary	PaO2/FiO2 ratio		at day 1, day 3, day 5	No
Secondary	Lowest PaO2/FiO2 during the first 5 days of the study		at 5 days	No
Secondary	Mean PaO2/FiO2 ratio during the first 5 days of the study		at 5 days	No
Secondary	Pulmonary static compliance, resistance and elastance		at day 1, day 2	No
Secondary	Duration of controlled mechanical ventilation		at day 30	No
Secondary	Total duration of mechanical ventilation (controlled/assisted)		at day 30	No
Secondary	Number of ventilatory-free days		at day 30	No
Secondary	Number of organ failure-free days		at day 30	No
Secondary	Vasopressor requirements		at 48 hours	No
Secondary	Mortality		at day 30	No