Clinical Trial Results:
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.
Summary
|
|
EudraCT number |
2020-003689-37 |
Trial protocol |
FR |
Global end of trial date |
24 Oct 2021
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
01 Jan 2023
|
First version publication date |
01 Jan 2023
|
Other versions |
|
Summary report(s) |
Final report_summary |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
RC20_0319
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT04611425 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
CHU de Nantes
|
||
Sponsor organisation address |
1 place Alexis Ricordeau, Nantes, France,
|
||
Public contact |
Direction Recherche et Innovation, CHU de Nantes, +33 0253482835, bp-prom-regl@chu-nantes.fr
|
||
Scientific contact |
Direction Recherche et Innovation, CHU de Nantes, +33 0253482835, bp-prom-regl@chu-nantes.fr
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
04 Oct 2022
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
24 Oct 2021
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
to assess the balance safety-efficacy of Remimazolam in the ICU during the first 8 hours after the beginning of infusion.
|
||
Protection of trial subjects |
Remimazolam is a novel benzodiazepine with promising pharmacokinetic and pharmacodynamic properties. It has been used in hundreds of patients worldwide in major cardiac and non-cardiac surgeries involving co-morbid patients, and in the critical care theatre. The safety data are extremely reassuring. The benefit/risk balance of the REHSCU study, in order to confirm the safety and efficacy of Remimazolam in the ICU in the context of a major hypnotic shortage in the setting of the COVID-19 pandemic, is highly favourable.
|
||
Background therapy |
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 shortages in masks, mechanical ventilation machines and common medications such as hypnotics. The reasons for such shortages 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 very short half-life that has been administered in patients undergoing major surgery, as well as in the intensive care unit. We propose to perform a pilot study assessing the benefit-risk ratio of Remimazolam in our critical care units during the COVID-19 pandemic. | ||
Evidence for comparator |
Non applicable. | ||
Actual start date of recruitment |
30 Nov 2020
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
France: 30
|
||
Worldwide total number of subjects |
30
|
||
EEA total number of subjects |
30
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
22
|
||
From 65 to 84 years |
8
|
||
85 years and over |
0
|
|
|||||||
Recruitment
|
|||||||
Recruitment details |
With the inclusion criteria we have adopted, thirty patients will therefore be required. Inclusion : 11 months. Follow-up : 5 days. | ||||||
Pre-assignment
|
|||||||
Screening details |
- Next-of-kin, Legal representative written informed consent or emergency consent - Affiliation with French social security system or beneficiary from such system | ||||||
Period 1
|
|||||||
Period 1 title |
Overall Trial (overall period)
|
||||||
Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
|
||||||
Blinding used |
Not blinded | ||||||
Arms
|
|||||||
Arm title
|
Remimazolam | ||||||
Arm description |
Remimazolam (CNS 7056) is a novel benzodiazepine. It is administered via a catheter (central or peripheric) intra-venously. Patients will receive Remimazolam for a maximum of 48 hours after the beginning of infusion. Sedation may be interrupted any time, if the patient no longer needs general anaesthesia. The attending physician will be responsible for this decision. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Remimazolam
|
||||||
Investigational medicinal product code |
|||||||
Other name |
|||||||
Pharmaceutical forms |
Solution for injection/infusion
|
||||||
Routes of administration |
Intravenous use
|
||||||
Dosage and administration details |
the initial dose of infusion will be within a 0.2-0.5 mg/min range. The dose of Remimazolam will be adapted to our protocol of sedation-analgesia protocol. The maximum dose of Remimazolam will be set at 1 mg/min.
|
||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall Trial
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All patients received Remimazolam. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Remimazolam
|
||
Reporting group description |
Remimazolam (CNS 7056) is a novel benzodiazepine. It is administered via a catheter (central or peripheric) intra-venously. Patients will receive Remimazolam for a maximum of 48 hours after the beginning of infusion. Sedation may be interrupted any time, if the patient no longer needs general anaesthesia. The attending physician will be responsible for this decision. |
|
|||||||
End point title |
Efficacy [1] | ||||||
End point description |
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).
|
||||||
End point type |
Primary
|
||||||
End point timeframe |
8 hours after the beginning of infusion
|
||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: it is a description of the study |
|||||||
|
|||||||
No statistical analyses for this end point |
|
|||||||
End point title |
Safety [2] | ||||||
End point description |
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.
|
||||||
End point type |
Primary
|
||||||
End point timeframe |
8 hours after the beginning of infusion
|
||||||
Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: it is a description of the study |
|||||||
|
|||||||
No statistical analyses for this end point |
|
|||||||
End point title |
Biological data | ||||||
End point description |
Routine laboratory tests
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
4 days
|
||||||
|
|||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
5 days
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall trial
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
08 Apr 2021 |
Addition of an emergency procedure for patient inclusion
Extension of the recruitment period by an additional 12 months |
||
06 May 2021 |
Update of the relative's information note following the implementation of the emergency procedure |
||
02 Jul 2021 |
Changement de PI sur site |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported. |