Clinical trial NCT04611425: REmimazolam Infusion in the Context of Hypnotic Shortage in the Critical Care Unit During the Pandemic of COVID-19: REHSCU Study
Official title: REmimazolam Infusion in the Context of Hypnotic Shortage in the Critical Care Unit During the Pandemic of COVID-19. The Non-randomized, Non-controlled, Pilot, Open, Mono-centric REHSCU Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Respiratory Failure
COVID-19
Trauma
Stroke
Sepsis
Shock
Keywords: Remimazolam
Sedation
Shortage
Critical care
COVID-19
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: Paion UK Ltd.
First posted: 2020-11-02
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Non-controlled
Primary purpose: SUPPORTIVE_CARE

Brief summary: The worldwide COVID-19 pandemic has led to a dramatic increase in the number of patients hospitalized in intensive care units for an acute respiratory failure in all countries. This situation has quickly led to massive shortage in masks, mechanical ventilation machines and common medications such as hypnotics. All countries over the world are currently experiencing a major shortage in basic hypnotic medications (propofol, midazolam) in the intensive care as well as in the operating theatre. The Principal Investigator proposes to perform a pilot study assessing the benefit-risk ratio of Remimazolam (a novel benzodiazepine with a short half-life) in the critical care units of Nantes University Hospital during the COVID-19 pandemic.

Detailed description: The worldwide COVID-19 pandemic has led to a dramatic increase in the number of patients hospitalized in intensive care units for an acute respiratory failure in all countries. This situation has quickly led to massive shortage in masks, mechanical ventilation machines and common medications such as hypnotics. The reasons for such shortage are multiple: dramatic increase of the demand, production discontinuation because of shutdowns in multiple countries, and withholding of products by producing countries. All countries over the world are currently experiencing a major shortage in basic hypnotic medications (propofol, midazolam) in the intensive care as well as in the operating theatre. Remimazolam is a novel benzodiazepine with a short half-life that has been administered in patients undergoing major surgery, as well as in the intensive care unit. The Principal Investigator proposes to perform a pilot study assessing the benefit-risk ratio of Remimazolam in the critical care units of Nantes University Hospital during the COVID-19 pandemic.

Eligibility criteria: 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

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.

Primary outcomes:
measure: composite endpoint including a combination of cardio-vascular and sedation events, from baseline (before infusion) to 8 hours, after the beginning of Remimazolam infusion
timeFrame: 8 hours after the beginning of infusion.
Secondary outcomes:
measure: Adverse Events (all grades), related to Remimazolam.
timeFrame: 5 days
measure: Heart rate
timeFrame: 3 days
measure: Arterial pressure
timeFrame: 3 days
measure: Dose of norepinephrine
timeFrame: 3 days
measure: Electrocardiogram (ECG)
timeFrame: 3 days
measure: Sedation.
timeFrame: 3 days
measure: Other sedatives.
timeFrame: 3 days
measure: Wake-up time.
timeFrame: 3 days
measure: Pharmacokinetics of Remimazolam and its metabolites (CNS 7054): Maximum Plasma Concentration.
timeFrame: 3 days
measure: Pharmacodynamics Remimazolam and its metabolites (CNS 7054): steady state plasma levels and elimination.
timeFrame: 3 days
measure: Laboratory parameters : blood gas
timeFrame: 4 days
measure: Laboratory parameters: haemoglobin
timeFrame: 4 days
measure: Laboratory parameters: platelet count
timeFrame: 4 days
measure: Laboratory parameters: white blood cell count
timeFrame: 4 days
measure: Laboratory parameters: ionogram
timeFrame: 4 days
measure: Laboratory parameters: creatinine
timeFrame: 4 days
measure: Laboratory parameters: bilirubin
timeFrame: 4 days
measure: Laboratory parameters: albumin
timeFrame: 4 days
measure: Laboratory parameters: liver enzymes
timeFrame: 4 days
measure: Laboratory parameters: phosphorus
timeFrame: 4 days
measure: Laboratory parameters: magnesium
timeFrame: 4 days
measure: Extubation failure defined as the need to intubate a patient in the 96 hours following extubation.
timeFrame: 28 days
measure: Length of Mechanical ventilation.
timeFrame: 28 days
measure: Death.
timeFrame: 28 days
Other outcomes:
Locations:
city: Nantes
country: France
facility: CHU de Nantes
Study officials:
affiliation: Nantes University Hospital
name: Raphaël CINOTTI, MD
role: PRINCIPAL_INVESTIGATOR
References: