Emergence DeliriumPhase 3AGINASALNCT05324852
AGItated Patients Management: intraNASAL Midazolam vs Intramuscular Loxapine
A Phase 3 study testing Intranasal midazolam and Intramuscular loxapine in people with Emergence Delirium, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Emergence Delirium
- What is being tested?
- Intranasal midazolam and Intramuscular loxapine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteFrance
- Study dates
- 9 Apr 2023to 23 Apr 2024
- Phase
- Phase 3
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: AGItated Patients Management: intraNASAL Midazolam vs Intramuscular Loxapine, a Randomized Non Inferiority Trial
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.
Read the 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.
- Conditions
- Emergence Delirium
- Being tested
- Intranasal midazolam, Intramuscular loxapine
- Medical subject headings
- Emergence Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intranasal midazolamDrug
Also called Midazolam
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
Intramuscular loxapineDrug
Also called Loxapine
Loxapine, 100mg, injectable solution in 50mg/2ml intramuscular, intra muscular administration, one time
| Study group | Role | What they receive |
|---|---|---|
| Intranasal midazolam | Experimental | 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 Receives: Drug: Intranasal midazolam |
| Intramuscular loxapine | Active comparator | Loxapine, 100mg, injectable solution in 50mg/2ml intramuscular, intra muscular administration, one time Receives: Drug: Intramuscular loxapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 15 minutes
Secondary outcomes (7)
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.
Measured: 240 minutes
Number of deceased patients
mortality at 24 hours
Measured: 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
Measured: 240 minutes
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.
Measured: 15,60,120 and 240 minutes
level of sedation obtained by loxapine or midazolam.
Proportion of patients with additional sedation required
Measured: 15 minutes
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.
Measured: 15 min and 240 min
Improvement of agitation
The proportion of patients with sufficient improvement of agitation at 15 minutes defined by a RASS < -1
Measured: 15 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2022
- Study start9 Apr 2023
- Primary completion9 Apr 2023
- Study completion23 Apr 2024
Why it stopped: Sponsor decision:
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Emergence DeliriumStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Intramuscular loxapine versus intranasal midazolam
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Lariboisière-Saint Louis clinical research unit
- Responsible party
- Sponsor
- Investigators
- Frédéric Adnet, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05324852
- Sponsor's protocol ID
- P160947J
- Acronym
- AGINASAL
- Status last verified
- May 2024
- First submitted
- 21 Mar 2022
- Last updated
- 28 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AGItated Patients Management: intraNASAL Midazolam vs Intramuscular Loxapine, a Randomized Non Inferiority Trial
- ClinicalTrials.gov ID
- NCT05324852
- Acronym / sponsor ID
- AGINASAL / P160947J
- Conditions
- Emergence Delirium
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision:
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Lariboisière-Saint Louis clinical research unit
- Study start
- 9 Apr 2023 (actual)
- Primary completion
- 9 Apr 2023 (actual)
- Study completion
- 23 Apr 2024 (actual)
- First posted
- 12 Apr 2022 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Intramuscular loxapine versus intranasal midazolam
| Arm | Type | Receives |
|---|---|---|
| Intranasal midazolam | Experimental | Drug: Intranasal midazolamMidazolam, 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 |
| Intramuscular loxapine | Active comparator | Drug: Intramuscular loxapineLoxapine, 100mg, injectable solution in 50mg/2ml intramuscular, intra muscular administration, one time |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
- Agitation Pain Tolerance Tachypnea ( fr > 20)
- 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.
Key exclusion criteria (14 listed)
- 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 :
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 |
|---|---|---|
| Intranasal midazolamAlso: MidazolamMidazolam, 5 mg, injectable solution in 5mg/ml, intranasal administration, atomize into nose with Mucosal Atomizer Device (MAD) 5mg(1ml) up each nostril , one time | Drug | Intranasal midazolam |
| Intramuscular loxapineAlso: LoxapineLoxapine, 100mg, injectable solution in 50mg/2ml intramuscular, intra muscular administration, one time | Drug | Intramuscular loxapine |
Primary outcome
Evolution of agitation
Time frame: 15 minutes
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).
7 secondary outcomes
Incidence of adverse events following the use of loxapine or midazolam
Time frame: 240 minutes
Number of deceased patients
Time frame: 24 hours
Number, type and severity level of adverse events
Time frame: 240 minutes
level of sedation obtained by loxapine or midazolam.
Time frame: 15,60,120 and 240 minutes
level of sedation obtained by loxapine or midazolam.
Time frame: 15 minutes
feelings of health providers with Qualitative research.
Time frame: 15 min and 240 min
Improvement of agitation
Time frame: 15 min
Results and safety
The study was stopped early (reason given: Sponsor decision:). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2024.
- Individual participant dataSharing planned: No
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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.
Frédéric Adnet, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intranasal midazolam and Intramuscular loxapine in people with Emergence Delirium, run by Assistance Publique - Hôpitaux de Paris 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 7 inclusion and 14 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: stopped early, as of the sponsor's last update on 28 May 2024. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 was stopped early (reason given: Sponsor decision:). Results are not available in the source record.
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?
Evolution of agitation (time frame: 15 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 May 2024.