general anaesthesia in ICU MedDRA version: 21.1 Level: PT Classification code 10021723 Term: Induction and maintenance of anaesthesia System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Product Name: Remimazolam
Product Code: PRD2518686
Pharmaceutical Form: Powder for solution for infusion
Sponsors
CHU de Nantes
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: PRE-INCLUSION CRITERIA - Next-of-kin, Legal representative written informed consent - affiliation with French social security system or beneficiary from such system INCLUSION CRITERIA - Patients at least 18 years old - Inclusion in the first 96 hours after ICU admission, after clinical stabilization according to the attending physician’s discretion. - Expected duration of general anaesthesia = 24 hours Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: -Patients more than 85 years-old -Refusal to participate -Severe patients with moribund state within the 24 hours after admission to the ICU -Withdrawal of Life Sustaining Therapies within the 24 hours after admission to the ICU -Any pregnant or breast-feeding patient, -Patients with known anaphylactic reactions to benzodiazepines, flumazenil, or a medical condition such that these agents are contraindicated (according to local label) -Patients with allergy/hypersensitivity to bovine lactose, dextran or any other excipient in the remimazolam product -Presence of acute alcoholic or illicit drug intoxication or benzodiazepine intoxication -Inclusion in another clinical (drug) trial -Patient under guardianship or trusteeship -Patient under judicial protection -Severe hepatic impairment defined as a Child-Pugh score > 10.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to assess the balance safety-efficacy of Remimazolam in the ICU during the first 8 hours after the beginning of infusion.;Secondary Objective: -Adverse Events (all grades), related to Remimazolam -hemodynamic stability -the level of sedation -the necessity to use or switch to other sedatives during the 48-hour time-frame -laboratory parameters -length of mechanical ventilation -extubation failure -steady state plasma levels and elimination of Remimazolam and its main metabolite -wake-up time (if applicable) -in-ICU mortality or at Day-28 if the patient is not discharged.;Primary end point(s): The primary endpoint is a composite endpoint including a combination of cardio-vascular and sedation events, from baseline (before infusion) to 8 hours, after the beginning of Remimazolam infusion. Since the patient’s clinical situation could rapidly evolved in the ICU, we chose to assess these endpoints during a short time-frame. 1) Safety. Cardiovascular event. Hypotension will be defined as a Mean Arterial Pressure =65mmHg or an increase =50% of the dose of norepinephrine (if appropriate), sustained over one hour after the beginning of Remimazolam. 2) Efficacy. Sedation event. We will check if Remimazolam provides an adequate level of sedation assessed with the Richmond Assessment Sedation Scale. The level of sedation will be set by the attending physician and is usually set at-1/0. We will also monitor the need to use standard hypnotic drugs within this time frame as rescue medication in case of Remimazolam inefficacy (propofol, midazolam, dexmedetomidine).;Timepoint(s) of evaluation of this end point: from baseline (before infusion) to 8 hours, after the beginning of Remimazolam infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints will be assessed as follows. These endpoints will be assessed the day of the initiation of Remimazolam, during the infusion, and at various time-points during the ICU. -Adverse Events observed during the 48-hour infusion and up to 3 days after end of dosing Adverse Event of Special Interest that will be monitored are the cardio-vascular events (hypotension, bradycardia), from the beginning to the end of Remimazolam infusion. An exhaustive monitoring of Adverse Events will be performed from Day-0 (inclusion), Day-1 and Day-2 (during infusion), to Day-5 (3 days after discontinuation). Owing to the very short half-life of Remimazolam, only adverse reaction monitoring will be performed afterwards. -Hemodynamic stability. Heart rate, systolic, diastolic and mean arterial pressure, dose of norepinephrine, modification of ECG. From Day-1 to Day-3 (ie 24 hours after the end of infusion). -Sedation. The level of sedation will be assessed with clinical scales such as Richmond Assessment Sedation Scale, Bispectral Index (when available). The monitoring with Bispectral Index, will be left at the attending physician’s discretion. From Day-1 to Day-3 (ie 24 hours after the end of infusion). -Other sedatives. During the infusion, the dose of Remimazolam will be monitored. The necessity to use or switch to other sedatives (midazolam, dexmedetomidine, propofol) in case of remimazolam inefficacy, will be monitored. From Day-1 to Day-3 (ie 24 hours after the end of infusion). -We will collect the wake-up time (in minutes) defined as Richmond Assessment Sedation Scale 4 of -1/0, only in non-neurologic patients and if general anesthesia is definitely stopped at the end of remimazolam infusion. From Day-1 to Day-3 (ie 24 hours after the end of infusion). -Pharmacokinetics and pharmacodynamics of Remimazolam and its metabolites, will be measured during the infusion and at the end. We will perform 9 Pharmocokinetic blood samplings du | — |
Countries
France
Contacts
Public ContactDirection Recherche et Innovation
CHU de Nantes
Outcome results
None listed