Sedation in Mechanically Ventilated Paediatric Patients 3 to 17 (Less than 18) Years Old MedDRA version: 20.0 Level: PT Classification code 10039897 Term: Sedation System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: LLT Classification code 10049683 Term: Monitored anesthesia care sedation System Organ Class: 100000004865 MedDRA version: 21.1 Level: LLT Classification code 10062825 Term: Monitored anaesthesia care sedation System Organ Class: 100000004865
Conditions
Sponsors
Sedana Medical AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Paediatric patients at least 3 years to 17 (less than 18, patients who will turn 18 years during the study [including follow-up] will not be included) years at the time of randomisation, admitted to an ICU/with planned ICU admission. 2. Expected mechanical (invasive) ventilation and sedation for at least 12 hours. 3. Informed consent obtained from the patient, patient’s legal guardian(s) as required by local regulations. Where applicable, assent obtained from the patient to participate in the clinical study. 4. Germany only: Women of childbearing potential who are sexually active: The patient does already use a highly effective contraception method or agrees to use a highlyeffective contraception method from signing the informed consent form (screening) until the operation / study treatment. According to Clinical Trials Facilitation Group (CTFG) recommendations, methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) • progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) • intrauterine device • intrauterine hormone-releasing system (IUS) • bilateral tubal occlusion • vasectomised partner • sexual abstinence or absence of sexual relations with men Are the trial subjects under 18? yes Number of subjects for this age range: 100 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Ongoing seizures requiring acute treatment. 2. Continuous sedation for more than 72 hours at time of randomisation. 3. Less than 24 hours post cardiopulmonary resuscitation. 4. Uncompensated circulatory shock. 5. Known hypersensitivity to isoflurane or to other halogenated anaesthetics (such as halothane), benzodiazepines, non-investigational medicinal product(s) (analgesics, additional rescue sedatives that may be required during the study) or to any of their formulation ingredients. 6. Known or suspected genetic susceptibility to malignant hyperthermia. 7. Patients with acute asthma or obstructive lung disease symptoms requiring treatment at inclusion. 8. Patient with tidal volumes below 30 mL or above 800 mL. 9. Inability to perform reliable COMFORT-B assessment in the opinion of the Investigator e.g. due to (not limited to): Severe traumatic brain injury, intracranial pathology (tumour, haemorrhage, infections), with a profound effect on the level of consciousness, severe mental retardation, major congenital anomalies of the central nervous system, severe myasthenia gravis, spinal muscular atrophy, or other severe neurologic disease, ongoing neuromuscular blockade which precludes COMFORT-B scoring. 10. Patients with intracranial pressure (ICP) monitoring or with suspected increase in ICP 11. Patients with treatment-induced whole-body hypothermia. 12. Patients with pheochromocytoma. 13. Patients with prolonged QT interval or with significant risk for prolonged QT interval. 14. Patient not expected to survive next 48 hours or not committed to full medical care. 15. Female patients who are pregnant or breast-feeding. 16. Previous participation in the study (a patient can only participate once). 17. Known participation in any other clinical study that included drug treatment within three months of the first administration of the IMP. 18. Any for the study relevant medical history, or ongoing clinically significant disease, disorder or laboratory result which, in the opinion of the Investigator, precludes participation in the study for medical or ethical reasons.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The primary endpoint assessment will start 2 hours after initiating study sedative treatment (or in the case of ongoing sedation, 2 hours after terminating ongoing sedatives). The primary endpoint assessment will be collected either until the study treatment is replaced with the standard treatment (at 48± 6 hours from study treatment initiation) or when the wake-up for extubation is started, whichever comes first.;Main Objective: 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 Objective: Secondary objectives, efficacy • 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 and other sedatives in isoflurane- vs midazolam-treated patients. Secondary objectives, safety Please see protocol;Primary end point(s): Percentage of time of adequately maintained sedation within the COMFORT-B interval (light, moderate or deep sedation) prescribed at randomisation, monitored every 2 hours for a minimum of 12 hours (up to 48 hours ± 6 hours). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints, efficacy • Dose of opiates, study drugs and other analgesics required, from first blinded COMFORT-B assessment (at +2 hours) to end of study treatment period, given per 24 hours. • Mean dose of study drugs, opiates and other analgesics required, during the last 4 hours of study treatment, as compared to the first 4 hours of study treatment after first blinded COMFORT-B assessment. • Mean dose of rescue propofol (mg/kg/24 hours) and mean dose of rescue ketamine/es- ketamine (converted to ketamine-equivalents mg/kg/24 hours), and mean dose of a2- adrenergic agonists (mg/kg/24 hours) to maintain the COMFORT-B score in the individually prescribed range, in isoflurane- vs midazolam-treated children (time window: from 2 hours after initiating study sedative treatment to end of sedative treatment). • Number of doses of rescue sedation (propofol, ketamine, es-ketamine) given per 24 hours from first blinded COMFORT-B assessment (at +2 hours) to end of study treatment period. Secondary endpoints, safety • Time from end of study drug administration to extubation if study drug is terminated for extubation. • Proportion of observations with spontaneous breathing efforts during study treatment. • Need for additional inotropic/vasopressor agent and change in VIS score during study treatment period compared to baseline. • Presence of withdrawal symptoms as assessed using the SOS-PD scale in patients exposed to more than a total of 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. • Presence of delirium as assessed using the SOS-PD scale in patients admitted to the ICU for at least 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. • Proportion of patients experiencing psychomotor dysfunction or neurological symptoms during sedati | — |
Countries
France, Germany, Spain, Sweden
Contacts
Public Contactclinical@sedanamedical.com
Sedana Medical AB
Outcome results
None listed