Acute Respiratory FailurePhase 2REHSCUNCT04611425
REmimazolam Infusion in the Context of Hypnotic Shortage in the Critical Care Unit During the Pandemic of COVID-19: REHSCU Study
A Phase 2 study testing Remimazolam in people with Acute Respiratory Failure and COVID-19, run by Nantes University Hospital at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Acute Respiratory Failure, COVID-19, Trauma
- What is being tested?
- Remimazolam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 30 Nov 2020to 22 Oct 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Patient under guardianship or trusteeship
- Patient under judicial protection
- Severe hepatic impairment defined as a Child-Pugh score > 10.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this 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
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.
Read the 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.
- Being tested
- Remimazolam
- Keywords
- Remimazolam, Sedation, Shortage, Critical care, COVID-19
- Medical subject headings
- COVID-19, Wounds and Injuries, Stroke, Sepsis, Shock
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemimazolamDrug
Also called Remimazolam (CNS 7056)
Patients will receive an infusion of Remimazolam for a maximum duration of 48 hours. The dose of Remimazolam will be adapted according to the ICU units protocol of analgesia-sedation management, based on validated scale (Richmond Assessment Sedation Scale). Owing to previous data gathered through a previous study in Japan, the initial dose of infusion will be within a 0.2-0.5 mg/min range. The dose of Remimazolam can be increased or decreased by 0.1mg/min when needed. The maximum dose of Remimazolam will be set at 1 mg/min.
| Study group | Role | What they receive |
|---|---|---|
| Remimazolam | Experimental | Patients will receive an infusion of Remimazolam for a maximum duration of 48 hours.
The dose of Remimazolam will be adapted according to our ICU protocol of analgesia-sedation management, based on validated scale (Richmond Assessment Sedation Scale) Receives: Drug: Remimazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
composite endpoint including a combination of cardio-vascular and sedation events, from baseline (before infusion) to 8 hours, after the beginning of Remimazolam infusion
For 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.
For Efficacy: Sedation event: the investigator 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. The investigator will also monitor the need to use standard hypnotic drugs within this time frame as further medication (propofol, midazolam, dexmedetomidine) in case of Remimazolam inefficacy (Richmond Assessment Sedation Scale).
Measured: 8 hours after the beginning of infusion.
Secondary outcomes (24)
Adverse Events (all grades), related to Remimazolam.
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).
Measured: 5 days
Heart rate
Hemodynamic stability follow-up of heart rate, from day1 to day3.
Measured: 3 days
Arterial pressure
Hemodynamic stability follow-up with systolic, diastolic and mean arterial pressure from day1 to day3.
Measured: 3 days
Dose of norepinephrine
Hemodynamic stability follow-up with the dose of norepinephrine from day1 to day3.
Measured: 3 days
Electrocardiogram (ECG)
Hemodynamic stability follow-up with electrocardiogram from day1 to day3.
Measured: 3 days
Sedation.
The level of sedation will be assessed with clinical scale (Richmond Assessment Sedation Scale, scores from -5:unarousable to+4 : Combative or Bispectral Index, index from 100 (awake subject) to 0 (very deep sleep) .From day1 to day3.
Measured: 3 days
Other sedatives.
The use or switch to other sedatives (midazolam, dexmedetomidine, propofol) in case of remimazolam inefficacy, will be monitored, from day1 to day3.
Measured: 3 days
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.
Measured: 3 days
Pharmacokinetics of Remimazolam and its metabolites (CNS 7054): Maximum Plasma Concentration.
maximum plasma concentration of Remimazolam and its metabolites, measured during the infusion and at the end. 9 Pharmacokinetic blood samplings during the infusion, and at Day-3, after Remimazolam discontinuation. In total 9 (nine) blood samples of 2 ml will be collected during the 48-hour infusion and during elimination phase (up to 24 hours post Remimazolam infusion).
Measured: 3 days
Pharmacodynamics Remimazolam and its metabolites (CNS 7054): steady state plasma levels and elimination.
measured during the infusion and at the end. 9 Pharmacodynamics blood samplings during the infusion, and at Day-3, after Remimazolam discontinuation. In total 9 (nine) blood samples of 2 ml will be collected during the 48-hour infusion and during elimination phase (up to 24 hours post Remimazolam infusion).
Measured: 3 days
Laboratory parameters : blood gas
Routine laboratory tests for blood gas will be made within this time frame: from day0 to day3.
Measured: 4 days
Laboratory parameters: haemoglobin
Routine laboratory tests for haemoglobin will be made within this time frame: from day0 to day3.
Measured: 4 days
Laboratory parameters: platelet count
Routine laboratory tests for platelet count will be made within this time frame: from day0 to day3.
Measured: 4 days
Laboratory parameters: white blood cell count
Routine laboratory tests for white blood cell count will be made within this time frame: from day0 to day3.
Measured: 4 days
Laboratory parameters: ionogram
Routine laboratory tests for ionogram will be made within this time frame: from day0 to day3.
Measured: 4 days
Laboratory parameters: creatinine
Routine laboratory tests for creatinine will be made within this time frame: from day0 to day3.
Measured: 4 days
Laboratory parameters: bilirubin
Routine laboratory tests for bilirubin will be made within this time frame: from day0 to day3.
Measured: 4 days
Laboratory parameters: albumin
Routine laboratory tests for albumin will be made within this time frame: from day0 to day3.
Measured: 4 days
Laboratory parameters: liver enzymes
Routine laboratory tests for liver enzymes will be made within this time frame: from day0 to day3.
Measured: 4 days
Laboratory parameters: phosphorus
Routine laboratory tests for phosphorus will be made within this time frame: from day0 to day3.
Measured: 4 days
Laboratory parameters: magnesium
Routine laboratory tests for magnesium will be made within this time frame: from day0 to day3.
Measured: 4 days
Extubation failure defined as the need to intubate a patient in the 96 hours following extubation.
Extubation failure will be defined as the need to intubate a patient in the 96 hours following extubation.
Measured: 28 days
Length of Mechanical ventilation.
Defined as the duration between the initiation and the successful weaning of mechanical ventilation. From Day-1 to ICU discharge or Day-28
Measured: 28 days
Death.
in the ICU or at Day-28 if the patient is not discharged
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2020
- Study start30 Nov 2020
- Primary completion2 Dec 2020
- Study completion22 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory FailureStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Non-controlled
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Paion UK Ltd.
- Responsible party
- Sponsor
- Investigators
- Raphaël CINOTTI, MD, Principal investigator, Nantes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04611425
- Sponsor's protocol ID
- RC20_0319
- Acronym
- REHSCU
- Status last verified
- Oct 2021
- First submitted
- 7 Oct 2020
- Last updated
- 4 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Grillot N, Vourc'h M, Hourmant Y, Bouras M, Rozec B, Rouhani A, Stoehr T, Jobert A, Roquilly A, Cinotti R. A phase 2 open-label pilot study of Remimazolam for sedation in critically ill patients. Anaesth Crit Care Pain Med. 2025 May;44(3):101510. doi: 10.1016/j.accpm.2025.101510. Epub 2025 Mar 31.
PubMed 40174701
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04611425
- Acronym / sponsor ID
- REHSCU / RC20_0319
- Keywords
- Remimazolam, Sedation, Shortage, Critical care, COVID-19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Collaborators
- Paion UK Ltd.
- Study start
- 30 Nov 2020 (actual)
- Primary completion
- 2 Dec 2020 (actual)
- Study completion
- 22 Oct 2021 (actual)
- First posted
- 2 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Non-controlled
| Arm | Type | Receives |
|---|---|---|
| Remimazolam | Experimental | Drug: RemimazolamPatients will receive an infusion of Remimazolam for a maximum duration of 48 hours. The dose of Remimazolam will be adapted according to our ICU protocol of analgesia-sedation management, based on validated scale (Richmond Assessment Sedation Scale) |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
- Patient under guardianship or trusteeship
- Patient under judicial protection
Key exclusion criteria (8 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RemimazolamAlso: Remimazolam (CNS 7056)Patients will receive an infusion of Remimazolam for a maximum duration of 48 hours. The dose of Remimazolam will be adapted according to the ICU units protocol of analgesia-sedation management, based on validated scale (Richmond Assessment Sedation Scale). Owing to previous data gathered through a previous study in Japan, the initial dose of infusion will be within a 0.2-0.5 mg/min range. The dose of Remimazolam can be increased or decreased by 0.1mg/min when needed. The maximum dose of Remimazolam will be set at 1 mg/min. | Drug | Remimazolam |
Primary outcome
composite endpoint including a combination of cardio-vascular and sedation events, from baseline (before infusion) to 8 hours, after the beginning of Remimazolam infusion
Time frame: 8 hours after the beginning of infusion.
For 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. For Efficacy: Sedation event: the investigator 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. The investigator will also monitor the need to use standard hypnotic drugs within this time frame as further medication (propofol, midazolam, dexmedetomidine) in case of Remimazolam inefficacy (Richmond Assessment Sedation Scale).
24 secondary outcomes
Adverse Events (all grades), related to Remimazolam.
Time frame: 5 days
Heart rate
Time frame: 3 days
Arterial pressure
Time frame: 3 days
Dose of norepinephrine
Time frame: 3 days
Electrocardiogram (ECG)
Time frame: 3 days
Sedation.
Time frame: 3 days
Other sedatives.
Time frame: 3 days
Wake-up time.
Time frame: 3 days
Pharmacokinetics of Remimazolam and its metabolites (CNS 7054): Maximum Plasma Concentration.
Time frame: 3 days
Pharmacodynamics Remimazolam and its metabolites (CNS 7054): steady state plasma levels and elimination.
Time frame: 3 days
Laboratory parameters : blood gas
Time frame: 4 days
Laboratory parameters: haemoglobin
Time frame: 4 days
Laboratory parameters: platelet count
Time frame: 4 days
Laboratory parameters: white blood cell count
Time frame: 4 days
Laboratory parameters: ionogram
Time frame: 4 days
Laboratory parameters: creatinine
Time frame: 4 days
Laboratory parameters: bilirubin
Time frame: 4 days
Laboratory parameters: albumin
Time frame: 4 days
Laboratory parameters: liver enzymes
Time frame: 4 days
Laboratory parameters: phosphorus
Time frame: 4 days
Laboratory parameters: magnesium
Time frame: 4 days
Extubation failure defined as the need to intubate a patient in the 96 hours following extubation.
Time frame: 28 days
Length of Mechanical ventilation.
Time frame: 28 days
Death.
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Derived from this study: PubMed 40174701Grillot N, Vourc'h M, Hourmant Y, Bouras M, Rozec B, Rouhani A, Stoehr T, Jobert A, Roquilly A, Cinotti R. A phase 2 open-label pilot study of Remimazolam for sedation in critically ill patients. Anaesth Crit Care Pain Med. 2025 May;44(3):101510. doi: 10.1016/j.accpm.2025.101510. Epub 2025 Mar 31.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raphaël CINOTTI, MD principal investigator
Nantes University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Remimazolam in people with Acute Respiratory Failure and COVID-19, run by Nantes University Hospital at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: 8 hours after the beginning of infusion.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04611425, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.