Efficacy and Safety of Inhaled Isoflurane Delivered Via the Sedaconda ACD-S Compared to Intravenous Propofol for Sedation of Mechanically Ventilated Intensive Care Unit Adult Patients (INSPiRE-ICU1)

Sedana Medical277 enrolled

Overview

This is a study to compare safety and efficacy of inhaled isoflurane administered via the Sedaconda ACD-S device system versus intravenous propofol for sedation of mechanically ventilated patients in the Intensive Care Unit (ICU) setting.

This is a phase 3, multicenter, randomized, controlled, open-label, assessor-blinded study to evaluate the efficacy and safety of inhaled isoflurane delivered via the Sedaconda ACD-S compared to intravenous propofol for sedation of mechanically ventilated Intensive Care Unit (ICU) adult patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

277

Conditions

Sedation

Interventions

IsofluraneDRUG

Inhaled isoflurane administered by Sedaconda ACD-S

PropofolDRUG

Intravenous infusion of propofol

Isoflurane (run-ins)DRUG

Inhaled isoflurane administered by Sedaconda ACD-S 3-5 run-in patients were enrolled at each site prior to randomization

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adults ≥18 years of age; * Patients who are anticipated to require \>12 hours of invasive mechanical ventilation and continuous sedation in the ICU; and * Receipt of continuous sedation due to clinical need for sedation to RASS \<0. Exclusion Criteria: * Need for RASS -5; * Sedation for invasive mechanical ventilation immediately prior to Baseline for \>72 hours; * Severe neurological condition before ICU admission that causes the patient to lack ability to participate in the study (ie, unable to be assessed for RASS and CPOT); * Ventilator tidal volume \<200 or \>1000 mL at Baseline; * Need for extracorporeal membrane oxygenation (ECMO), extracorporeal CO2 removal (ECCO2R), high frequency oscillation ventilation (HFOV), or high frequency percussive ventilation (HFPV) at Screening; * Comfort care only (end of life care); * Contraindication to propofol or isoflurane; * Known or family history of MH; * Severe hemodynamic compromise, defined as the need for norepinephrine ≥0.3 mcg/kg/min (or equivalent vasopressor dose) to maintain blood pressure within acceptable range, assumed to be mean arterial pressure ≥65 mmHg unless prescribed clinically; * Allergy to isoflurane or propofol, or have propofol infusion syndrome. * History of ventricular tachycardia/Long QT Syndrome; * Requirement of IV benzodiazepine or barbiturate administration for seizures or dependencies, including alcohol withdrawal * Neuromuscular disease that impairs spontaneous ventilation (eg, C5 or higher spinal cord injury, amyotrophic lateral sclerosis, etc); * Concurrent enrollment in another study that, in the Investigator's opinion, would impact the patient's safety or assessments of this study; * Participation in other study involving investigational drug(s) or devices(s) within 30 days prior to Randomization; * Anticipated requirement of treatment with continuous infusion of a neuromuscular blocking agent for \>4 hours; * Female patients who are pregnant or breast-feeding; * Imperative need for continuous active humidification through mechanical ventilation circuit; * Attending physician's refusal to include the patient; or * Inability to obtain informed consent.

Locations (14)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Emory University

Atlanta, Georgia, United States

University of Chicago

Chicago, Illinois, United States

Outcomes

Primary Outcomes

The Percentage of Time Sedation Depth is Maintained Within the Target Range, in Absence of Rescue Sedation, as Assessed According to the RASS Scale, in Isoflurane- vs Propofol-treated Patients

The Target Range is RASS -1 to -4. The Richmond Agitation-Sedation Scale (RASS) is used to measure the level of agitation or sedation in patients, particularly in critical care settings. It is a 10-point scale ranging from -5 to +4: +4 Combative - Violent, immediate danger to staff. +3 Very agitated - Pulls or removes tubes or catheters; aggressive. +2 Agitated - Frequent non-purposeful movement, fights ventilator. +1 Restless - Anxious but movements are not aggressive. 0 Alert and calm. -1 Drowsy - Not fully alert, but has sustained awakening (eye-opening/eye contact) to voice for more than 10 seconds. -2 Light sedation - Briefly awakens with eye contact to voice for less than 10 seconds. -3 Moderate sedation - Movement or eye opening to voice, but no eye contact. -4 Deep sedation - No response to voice, but movement or eye opening to physical stimulation. -5 Unarousable - No response to voice or physical stimulation.

Time frame: From start to end of study treatment (up to 48 (±6) hours)

Secondary Outcomes

Key Secondary: The Effect of Isoflurane vs Propofol on Use of Opioids During the Study Treatment Period

To compare the effect of isoflurane vs propofol on use of opioids during the study treatment period by measuring change in mean fentanyl-equivalent opioid dose during the study treatment period compared to mean opioid dose during the 60 minutes prior to baseline

Time frame: From 60 minutes prior to Baseline until end of study treatment (60 minutes + up to 48 (±6) hours)

Key Secondary: The Effect of Isoflurane vs Propofol on the Wake up Time at End of Study Drug Treatment

Time frame: Up to 4 hours after stop of study drug treatment (up to 54 (±6) hours)

Key Secondary: The Effect of Isoflurane vs Propofol on Cognitive Recovery After End of Study Drug Treatment

Cognitive recovery will be assessed by the 7-point scale of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU-7) at 60 (±10) minutes after end of study drug treatment in patients not re-sedated with benzodiazepine or propofol infusions. The scale ranges from 0 to 7, with higher scores indicating more severe delirium.

Data from ClinicalTrials.gov

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