Clinical trial NCT05324852: AGItated Patients Management: intraNASAL Midazolam vs Intramuscular Loxapine
Official title: AGItated Patients Management: intraNASAL Midazolam vs Intramuscular Loxapine, a Randomized Non Inferiority Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Emergence Delirium
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Lariboisière-Saint Louis clinical research unit
First posted: 2022-04-12
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Intramuscular loxapine versus intranasal midazolam
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Evolution of agitation
timeFrame: 15 minutes
Secondary outcomes:
measure: Incidence of adverse events following the use of loxapine or midazolam
timeFrame: 240 minutes
measure: Number of deceased patients
timeFrame: 24 hours
measure: Number, type and severity level of adverse events
timeFrame: 240 minutes
measure: level of sedation obtained by loxapine or midazolam.
timeFrame: 15,60,120 and 240 minutes
measure: level of sedation obtained by loxapine or midazolam.
timeFrame: 15 minutes
measure: feelings of health providers with Qualitative research.
timeFrame: 15 min and 240 min
measure: Improvement of agitation
timeFrame: 15 min
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Hôpital Avicenne
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Frédéric Adnet, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: