Effect & Safety of Inhaled Isoflurane vs IV Midazolam for Sedation in Mechanically Ventilated Children 3-17 Years Old
- Registration Number
- NCT04684238
- Lead Sponsor
- Sedana Medical
- Brief Summary
This is a study to compare safety and efficacy of inhaled isoflurane delivered by the AnaConDa-S versus intravenous midazolam for sedation in mechanically ventilated children admitted to an intensive care unit.
- Detailed Description
This is a phase III, multi-centre, prospective, randomized, active-controlled, assessor-blind study. Primary endpoint: percentage of time of adequately maintained sedation, in absence of rescue sedation, within the COMFORT-B interval (light, moderate, or deep sedation) prescribed at randomization, monitored every 2 hours for an expected minimum of 12 hours (up to 48 hours).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 97
- Patients at least 3 years to 17 (less than 18) years at the time of randomization, admitted to an ICU/with planned ICU admission.
- Expected mechanical (invasive) ventilation and sedation for at least 12 hours.
- Informed consent obtained from the patient, patient's legal guardian(s)
- Ongoing seizures requiring acute treatment.
- Continuous sedation for more than 72 hours at time of randomization.
- Less than 24 hours post cardiopulmonary resuscitation.
- Uncompensated circulatory shock.
- Known or suspected genetic susceptibility to malignant hyperthermia.
- Patients with acute asthma or obstructive lung disease symptoms requiring treatment at inclusion.
- Patient with tidal volume below 30 mL or above 800 mL.
- Inability to perform reliable COMFORT-B assessment in the opinion of the Investigator
- Patients with intracranial pressure (ICP) monitoring or with suspected increase in ICP
- Patients with treatment-induced whole-body hypothermia.
- Patients with pheochromocytoma.
- Patients with prolonged QT interval or with significant risk for prolonged QT interval.
- Patient not expected to survive next 48 hours or not committed to full medical care.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Drug: Midazolam Midazolam Midazolam for sedation in the ICU Drug: Isoflurane Isoflurane Volatile for sedation in the ICU
- Primary Outcome Measures
Name Time Method Percentage of time adequate sedation depth Minimum of 12 hours up to 48 hours (± 6 hours). To compare the percentage of time adequate sedation depth is maintained within the individually prescribed target range in absence of rescue sedation as assessed according to the COMFORT-B scale, in isoflurane vs midazolam treated paediatric patients for an expected minimum of 12 hours.
- Secondary Outcome Measures
Name Time Method Compare the 30 days/hospital mortality From start of study treatment up to 30 days Compare the 30 days/hospital mortality in isoflurane- vs midazolam-treated patients
Compare the proportion of time with spontaneous breathing During study treatment Compare the proportion of time with spontaneous breathing in isoflurane- vs midazolam treated patients.
Compare the use of opiates Minimum of 12 hours up to 48 hours (± 6 hours). Compare the use of opiates, and the development of tolerance to the sedative regimen as measured by the change in dose of study drug,opiates and other analgesics, over time in isoflurane- vs midazolam treated patients.
Compare the need for rescue sedatives Minimum of 12 hours up to 48 hours (± 6 hours). Compare the need for rescue sedatives and other sedatives in isoflurane- vs midazolam-treated patients.
Compare time from sedation termination to extubation Time from end of study drug administration to extubation Compare time from sedation termination to extubation in isoflurane- vs midazolam-treated patients.
Evaluate haemodynamic effect as indicated by inotropic/vasopressor agent During study treatment period compared to baseline Evaluate haemodynamic effect as indicated by inotropic/vasopressor agent administration in patients sedated with isoflurane compared with midazolam.
Evaluate the frequency of withdrawal symptom Patients exposed > 96 hours sedation (including pre-study sedation period) until the end of the 48-hour post study treatment monitoring or ICU discharge, whichever comes first. Evaluate the frequency of withdrawal symptoms in isoflurane- vs midazolam-treated patients.
Evaluate the frequency of delirium Patients admitted to the ICU ≥48 hours (including period prior to study enrolment) until the end of the 48-hour post study treatment monitoring or ICU discharge, whichever comes first. Evaluate the frequency of delirium in isoflurane- vs midazolam-treated patients
Evaluate the frequency of neurological symptoms or psychomotor dysfunction During study treatment and up to 48 hours after discontinuation of isoflurane and midazolam Evaluate the frequency of neurological symptoms or psychomotor dysfunction during and up to 48 hours after discontinuation of isoflurane and midazolam treatment, and the association with duration of treatment, and total exposure (MAC hours and midazolam doses) over time.
Compare ventilator-free days From start of study treatment up to 30 days Compare ventilator-free days up to 30 days in isoflurane- vs midazolam-treated patients.
Compare the time in ICU/hospital From start of study treatment up to 30 days Compare the time in ICU/hospital up to 30 days in isoflurane- vs midazolam-treated patients.
Compare the safety profile Baseline to end of study treatment, safety lab from baseline up to 48hrs post treatment, AEs from start study treatment up to day 30 Compare the safety profile in terms of experienced adverse events, safety laboratory values, blood gases, vital signs, body temperature and urinary output in isoflurane- vs midazolam-treated patients.
Compare ICU-free days From start of study treatment up to 30 days Compare ICU-free days up to 30 days in isoflurane- vs midazolam-treated patients.
Trial Locations
- Locations (24)
CHU de NANTES, Hôpital Mère-Enfant
🇫🇷Nantes, France
Hôpital Robert-Debré AP-HP
🇫🇷Paris, France
Hospital Infantil Universitario Niño Jesús Pediatric Intensive Care Unit
🇪🇸Madrid, Spain
Royal Manchester Children's Hospital
🇬🇧Manchester, United Kingdom
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Universitätsklinikum Jena
🇩🇪Jena, Germany
Hôpital Femme-Mère-Enfant Groupe Hospitalier Est
🇫🇷Lyon, France
Hôpitaux Universitaires Paris Sud Site Bicetre
🇫🇷Paris, France
Hôpitaux Universitaires de Strasbourg Hôpital de Hautepierre
🇫🇷Strasbourg, France
Centre Hospitalier Universitaire de Reims
🇫🇷Reims, France
Universitätsklinikum Hamburg-Eppendorf (UKE)
🇩🇪Hamburg, Germany
Universitätsklinikum Köln
🇩🇪Cologne, Germany
Hospital Universitario Reina Sofía
🇪🇸Córdoba, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Materno Infantil Sant Joan de Deu Hospital
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Regional Universitario, Carlos Haya
🇪🇸Málaga, Spain
Karolinska Universitetssjukhus Solna
🇸🇪Solna, Sweden
Hospital Universitario Virgen del Rocio de Sevilla
🇪🇸Sevilla, Spain
University Hospitals of Leicester NHS Trust
🇬🇧Leicester, United Kingdom
Universitätsklinik Freiburg
🇩🇪Freiburg, Germany
Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom