Sedation
Conditions
Keywords
sedation, mechanical ventilation, propofol, ICU, isoflurane
Brief summary
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.
Detailed description
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.
Interventions
DRUGIsoflurane
Inhaled isoflurane administered by Sedaconda ACD-S
DRUGPropofol
Intravenous infusion of propofol
Sponsors
Sedana Medical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | From start to end of study treatment (up to 48 (±6) hours) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Key Secondary: The Effect of Isoflurane vs Propofol on Use of Opioids During the Study Treatment Period | From 60 minutes prior to Baseline until end of study treatment (60 minutes + up to 48 (±6) hours) | 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. |
| Key Secondary: The Effect of Isoflurane vs Propofol on the Wake up Time at End of Study Drug Treatment | 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 | At 60 minutes (±10 minutes) after end of study drug treatment (up to 49 (±6) hours) | 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 |
| Key Secondary: The Effect of Isoflurane vs Propofol on Spontaneous Breathing Effort During the Study Drug Treatment Period | From start to end of study treatment, up to 48 (±6) hours | Proportion of ventilator parameter observations with spontaneous breathing efforts during the study drug treatment period |
| Other Secondary: The Effect of Isoflurane vs Propofol on Time From Sedation Termination to Extubation in Patients for Whom Study Drug is Terminated for Extubation | From end of study drug treatment to extubation (up to 7 Days after randomization) | — |
| Other Secondary: The Effect of Isoflurane vs Propofol on Days Alive and Free of Mechanical Ventilation Through Study Day 30 | From start of study treatment up to 30 days | — |
| Other Secondary: To Compare the Effect of Isoflurane vs Propofol on Days Alive and Free of the ICU | From start of study treatment up to 30 days | — |
| Other Secondary: The Effect of Isoflurane vs Propofol on Delirium and Coma Free Days Until 7 Days After End of Study Treatment | From start of study treatment until 7 days after end of treatment (up to 9 days post study drug treatment initiation) | — |
| Other Secondary: The Effect of Isoflurane vs Propofol on Mortality at 30 Days After Randomization | At 30 days after randomization | Participants reported represent participants that died between randomization and 30 days in the Safety population |
| Other Secondary: The Effect of Isoflurane vs Propofol on Mortality at 3 Months After Randomization | At 3 months after randomization | Participants reported represent participants that died between randomization and 3 months in the Safety population |
| Other Secondary: The Effect of Isoflurane vs Propofol on Mortality at 6 Months After Randomization | At 6 months after randomization | Participants reported represent participants that died between randomization and 6 months in the Safety population |
| Other Secondary: Sedaconda ACD-S Device Deficiencies in Patients Receiving Isoflurane | From start to end of study treatment (up to 48 (±6) hours) | — |
| Other Secondary: The Use of Restraints in Patients Receiving Isoflurane vs Propofol | From start to end of study treatment (up to 48 (±6) hours) | Incidence of restraints measured twice daily |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJeremy Beitler, M.D.
Columbia University
Participant flow
Pre-assignment details
3-5 run-in patients treated with isoflurane were enrolled at each site prior to randomization. Run-ins are not analyzed separately, only included in the safety population together with the randomized patients that received at least one dose of study drug. In total 47 run-ins (46 with at least one dose of study drug), 142 randomized isoflurane participants (127 with at least one dose of study drug) and 93 randomized propofol participants (87 with at least one dose of study drug).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 23 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 65.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 11 Participants |
| Race (NIH/OMB) White | 193 Participants |
| Region of Enrollment United States | 282 participants |
| Sex: Female, Male Female | 105 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 58 / 173 | 34 / 87 |
| other Total, other adverse events | 92 / 173 | 52 / 87 |
| serious Total, serious adverse events | 33 / 173 | 24 / 87 |
Outcome results
None listed