Back to resultsAGItated Patients Management: intraNASAL Midazolam vs Intramuscular Loxapine (AGINASAL)
Primary Purpose
Emergence Delirium
Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Intranasal midazolam
Intramuscular loxapine
Sponsored by
About this trial
This is an interventional treatment trial for Emergence Delirium
Eligibility Criteria
Inclusion Criteria:
- Age 18 to 60 years;
- Agitated Patient whose somatic or psychiatric aetiology cannot be diagnosed in an emergency situation and who need a sedation in a hospital emergency setting due to the presence of unmanageable agitation with 3 major criteria.
Major criteria :
Agitation Pain Tolerance Tachypnea ( fr > 20)
And 1 minor criteria among :
Sweating Tactile Hyperthermia Medical care Non compliance Lack of tiring Unusual Strenght Inappropriately clothed, nudity
• Medical insurance The protocol can start if the THREE major inclusion criteria and ONE of the minor inclusion criteria are checked PRESENT and ALL the non-inclusion criteria are checked no.
Exclusion Criteria:
Subjects who meet any of the following criteria will be excluded from randomization into the study:
- Pregnancy
- Prisoners
Contraindications to intranasal Midazolam or intramuscular Loxapine :
- Hypersensitivity to benzodiazepines or to any of the excipients (Sodium Chloride, Hydrochloric Acid, Sodium Hydroxide, Water for Injection)
- Known hypersensitivity to loxapine or to any of the excipients (Polysorbate 80, propylene glycol, 20% v/v hydrochloric acid, water for injections, Nitrogen (Inert gas)
- Individuals who are in comatose states or have central nervous system (CNS) depression due to alcohol or are taking other depressant drugs
- Individuals with severe depressive states, spastic diseases, and with Parkinson's disease, except in the case of dyskinesias due to levodopa treatment
- In combination with dopamine agonists except levodopa (amantadine, bromocriptine, lisuride, pergolide, piribedil, ropinirole, cabergoline, pramipexole, apomorphine) outside the patient with Parkinson's disease
- Individuals with a history of cerebrovascular accident or epilepsia
- Individuals in whom a significant elevation of blood pressure would constitute a serious hazard, such as patients with significant hypertension;
- Individuals with severe cardiac decompensation
- Patients with severe respiratory failure or acute respiratory depression
- Individuals with acute narrow angle glaucoma.
Sites / Locations
- Hôpital AvicenneRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Intranasal midazolam
Intramuscular loxapine
Arm Description
Midazolam, 5 mg, injectable solution in 5mg/ml, if weight < 50 kg : 5mg; if weight ≥50kg : 10mg, intranasal administration, atomize into nose with Mucosal Atomizer Device (MAD) 5mg(1ml) up each nostril , one time
Loxapine, 100mg, injectable solution in 50mg/2ml intramuscular, intra muscular administration, one time
Outcomes
Primary Outcome Measures
Evolution of agitation
The proportion of patients with sufficient improvement of agitation at 15 minutes defined by a reduction of at least 3 points on the CGI (Clinical Global Impression).
Secondary Outcome Measures
Incidence of adverse events following the use of loxapine or midazolam
The adverse effects over 240 minutes : oxygen desaturation [<90%], airway obstruction requiring intervention, tracheal intubation, cardiac arrhythmias, prolonged QTc interval, hypotension, extrapyramidal side effects, akathisia, and anaphylaxis.
Number of deceased patients
mortality at 24 hours
Number, type and severity level of adverse events
The adverse effects over 240 minutes : oxygen desaturation [<90%], airway obstruction requiring intervention, tracheal intubation, cardiac arrhythmias, prolonged QTc interval, hypotension, extrapyramidal side effects, akathisia, and anaphylaxis
level of sedation obtained by loxapine or midazolam.
The proportion of patients with sufficient improvement of agitation at 240 minutes defined by a reduction of at least 3 points on the CGI.
Proportion of patients clinically improved on the improvement subscale of the clinical global impressions scale at 15, 60, 120, and 240 minutes.
level of sedation obtained by loxapine or midazolam.
Proportion of patients with additional sedation required
feelings of health providers with Qualitative research.
Duration of violent and acute behavioural disturbance Staff injuries. Proportion of patients requiring the doctor to be called back.
Improvement of agitation
The proportion of patients with sufficient improvement of agitation at 15 minutes defined by a RASS < -1
Full Information
NCT ID
NCT05324852
First Posted
March 21, 2022
Last Updated
August 9, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Lariboisière-Saint Louis clinical research unit
1. Study Identification
Unique Protocol Identification Number
NCT05324852
Brief Title
AGItated Patients Management: intraNASAL Midazolam vs Intramuscular Loxapine
Acronym
AGINASAL
Official Title
AGItated Patients Management: intraNASAL Midazolam vs Intramuscular Loxapine, a Randomized Non Inferiority Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 14, 2023 (Actual)
Primary Completion Date
May 15, 2025 (Anticipated)
Study Completion Date
June 15, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Lariboisière-Saint Louis clinical research unit
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is a non-inferiority phase III randomized trial evaluating the effect of intranasal midazolam versus intramuscular loxapine on the rapid tranquilization of agitated patient in emergency department. Intranasal midazolam is safe and may allow a management of extreme agitation state and prevent adverse effects.
Detailed Description
This study is a prospective, multicenter, open-label randomized, controlled, parallel-group 2-arm phase III non-inferiority trial. Patients with agitation at emergency department will be randomized to two arms of treatment: one experimental arm with intranasal midazolam 5mg (investigational medicinal product), and one control arm with comparator treatment intramuscular loxapine 100mg. The duration of participation for each patient is at least 28 days (+7 days if follow-up not completed on D28). An endpoint Adjudication Committee will be scheduled.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Emergence Delirium
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Intramuscular loxapine versus intranasal midazolam
Masking
None (Open Label)
Allocation
Randomized
Enrollment
830 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intranasal midazolam
Arm Type
Experimental
Arm Description
Midazolam, 5 mg, injectable solution in 5mg/ml, if weight < 50 kg : 5mg; if weight ≥50kg : 10mg, intranasal administration, atomize into nose with Mucosal Atomizer Device (MAD) 5mg(1ml) up each nostril , one time
Arm Title
Intramuscular loxapine
Arm Type
Active Comparator
Arm Description
Loxapine, 100mg, injectable solution in 50mg/2ml intramuscular, intra muscular administration, one time
Intervention Type
Drug
Intervention Name(s)
Intranasal midazolam
Other Intervention Name(s)
Midazolam
Intervention Description
Midazolam, 5 mg, injectable solution in 5mg/ml, intranasal administration, atomize into nose with Mucosal Atomizer Device (MAD) 5mg(1ml) up each nostril , one time
Intervention Type
Drug
Intervention Name(s)
Intramuscular loxapine
Other Intervention Name(s)
Loxapine
Intervention Description
Loxapine, 100mg, injectable solution in 50mg/2ml intramuscular, intra muscular administration, one time
Primary Outcome Measure Information:
Title
Evolution of agitation
Description
The proportion of patients with sufficient improvement of agitation at 15 minutes defined by a reduction of at least 3 points on the CGI (Clinical Global Impression).
Time Frame
15 minutes
Secondary Outcome Measure Information:
Title
Incidence of adverse events following the use of loxapine or midazolam
Description
The adverse effects over 240 minutes : oxygen desaturation [<90%], airway obstruction requiring intervention, tracheal intubation, cardiac arrhythmias, prolonged QTc interval, hypotension, extrapyramidal side effects, akathisia, and anaphylaxis.
Time Frame
240 minutes
Title
Number of deceased patients
Description
mortality at 24 hours
Time Frame
24 hours
Title
Number, type and severity level of adverse events
Description
The adverse effects over 240 minutes : oxygen desaturation [<90%], airway obstruction requiring intervention, tracheal intubation, cardiac arrhythmias, prolonged QTc interval, hypotension, extrapyramidal side effects, akathisia, and anaphylaxis
Time Frame
240 minutes
Title
level of sedation obtained by loxapine or midazolam.
Description
The proportion of patients with sufficient improvement of agitation at 240 minutes defined by a reduction of at least 3 points on the CGI.
Proportion of patients clinically improved on the improvement subscale of the clinical global impressions scale at 15, 60, 120, and 240 minutes.
Time Frame
15,60,120 and 240 minutes
Title
level of sedation obtained by loxapine or midazolam.
Description
Proportion of patients with additional sedation required
Time Frame
15 minutes
Title
feelings of health providers with Qualitative research.
Description
Duration of violent and acute behavioural disturbance Staff injuries. Proportion of patients requiring the doctor to be called back.
Time Frame
15 min and 240 min
Title
Improvement of agitation
Description
The proportion of patients with sufficient improvement of agitation at 15 minutes defined by a RASS < -1
Time Frame
15 min
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18 to 60 years;
Agitated Patient whose somatic or psychiatric aetiology cannot be diagnosed in an emergency situation and who need a sedation in a hospital emergency setting due to the presence of unmanageable agitation with 3 major criteria.
Major criteria :
Agitation Pain Tolerance Tachypnea ( fr > 20)
And 1 minor criteria among :
Sweating Tactile Hyperthermia Medical care Non compliance Lack of tiring Unusual Strenght Inappropriately clothed, nudity
• Medical insurance The protocol can start if the THREE major inclusion criteria and ONE of the minor inclusion criteria are checked PRESENT and ALL the non-inclusion criteria are checked no.
Exclusion Criteria:
Subjects who meet any of the following criteria will be excluded from randomization into the study:
Pregnancy
Prisoners
Contraindications to intranasal Midazolam or intramuscular Loxapine :
Hypersensitivity to benzodiazepines or to any of the excipients (Sodium Chloride, Hydrochloric Acid, Sodium Hydroxide, Water for Injection)
Known hypersensitivity to loxapine or to any of the excipients (Polysorbate 80, propylene glycol, 20% v/v hydrochloric acid, water for injections, Nitrogen (Inert gas)
Individuals who are in comatose states or have central nervous system (CNS) depression due to alcohol or are taking other depressant drugs
Individuals with severe depressive states, spastic diseases, and with Parkinson's disease, except in the case of dyskinesias due to levodopa treatment
In combination with dopamine agonists except levodopa (amantadine, bromocriptine, lisuride, pergolide, piribedil, ropinirole, cabergoline, pramipexole, apomorphine) outside the patient with Parkinson's disease
Individuals with a history of cerebrovascular accident or epilepsia
Individuals in whom a significant elevation of blood pressure would constitute a serious hazard, such as patients with significant hypertension;
Individuals with severe cardiac decompensation
Patients with severe respiratory failure or acute respiratory depression
Individuals with acute narrow angle glaucoma.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Frédéric Adnet, MD, PhD
Phone
01 48 96 44 08
Email
frederic.adnet@avc.aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Eric Vicaut, MD, PhD
Phone
01.40.05.49.73
Email
sec.urc@lrb.aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frédéric Adnet, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Avicenne
City
Bobigny
ZIP/Postal Code
93000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frédéric Pr ADNET
Phone
148964408
Ext
+33
Email
frederic.adnet@aphp.fr
First Name & Middle Initial & Last Name & Degree
Sabine Dr GUINEMER
Phone
148964408
Ext
+33
Email
sabine.guinemer@aphp.fr
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
AGItated Patients Management: intraNASAL Midazolam vs Intramuscular Loxapine
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