AGItated Patients Management: intraNASAL Midazolam vs Intramuscular Loxapine

NCT05324852 | Terminated Phase 3

• 1 other identifier: P160947J
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Emergence Delirium

Outcome Measures

Primary Outcomes (1)

• 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).

  15 minutes

Secondary Outcomes (7)

• Incidence of adverse events following the use of loxapine or midazolam

  240 minutes

• Number of deceased patients

  24 hours

• Number, type and severity level of adverse events

  240 minutes

• level of sedation obtained by loxapine or midazolam.

  15,60,120 and 240 minutes

• level of sedation obtained by loxapine or midazolam.

  15 minutes

Study Arms (2)

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

Drug: Intranasal midazolam

Intramuscular loxapine

ACTIVE COMPARATOR

Loxapine, 100mg, injectable solution in 50mg/2ml intramuscular, intra muscular administration, one time

Drug: Intramuscular loxapine

Interventions

Intranasal midazolam DRUG

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

Also known as: Midazolam

Intranasal midazolam

Intramuscular loxapine DRUG

Loxapine, 100mg, injectable solution in 50mg/2ml intramuscular, intra muscular administration, one time

Also known as: Loxapine

Intramuscular loxapine

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Lariboisière-Saint Louis clinical research unit: collaborator

Study Sites (1)

Hôpital Avicenne

Bobigny, 93000, France

Location

MeSH Terms

Conditions

Emergence Delirium

Interventions

Midazolam; Loxapine

Condition Hierarchy (Ancestors)

Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dibenzoxazepines; Heterocyclic Compounds, 3-Ring

Study Officials

• Frédéric Adnet, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Intramuscular loxapine versus intranasal midazolam

Study Record Dates

• First Submitted: March 21, 2022
• First Posted: April 12, 2022
• Study Start: April 9, 2023
• Primary Completion: April 9, 2023
• Study Completion: April 23, 2024
• Last Updated: May 28, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)