Clinical trial NCT03216941: Randomised Trial Ketiapine Olanzapine Fast Sedation Agitated Patients Emergency Ward
Official title: Prospective Randomised Double Blind Trial of Ketiapine and Olanzapine Comparative Efficacy for Fast Sedation of Severely Agitated Patients in Emergency Psychiatric Ward
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Psychomotor Agitation
Psychiatric Disorder
Emergency Psychiatric
Tranquilizers
Keywords: Psychomotor agitation; Tranquilizing agents
Lead sponsor: Universidad Nacional de Rosario
Sponsor class: OTHER
First posted: 2017-07-13
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double-blind controlled trial to compare the effectiveness of intramuscular olanzapine and ketamine as first medication(s) used to treat patients with agitation caused by psychosis.
Primary purpose: TREATMENT

Brief summary: comparison of intramuscular olanzapine and ketamine efficacy as first medication for fast sedation of patients with agitation and aggressive behavior. Five hundred patients with agitation caused by psychiatric disorder were randomly assigned under double-blind conditions to receive olanzapine or ketiapine. The Overt Agitation Severity Scale, Overt Aggression Scale and Ramsay Sedation Scale will be applied within 12 hours after the first dosage.

Detailed description: double-blind controlled trial to compare effectiveness of intramuscular olanzapine and ketamine as first medication to fast sedation of patients with agitation caused by psychiatric conditions. Randomization will be performed by permuted blocks allocation in which ketiamine or olanzapine standard treatment will be assigned to blocks of five patients and distributed in this order: olanzapine and ketiamine. This assignment will be repeated until the total number of subjects (500) be reached.

agitation status will be operationalized using Overt Agitation Severity Scale Total Score (OASS) equal or greater than 20 and Overt Aggressive Scale (OAS) with four or more positive items. Full physical and neurological examination will be completed as soon as possible, whenever patient is considered eligible for the study. Written Informed consent should be provided before and after participating in this study, and should be reviewed and approved by the institutional review board. Written consent obtained before admission to the emergency ward by legal guardian and after 12 hours by the patient (whenever he or she is is able to understand the information) or by the guardian. This study will comply with principles of the Declaration of Helsinki and Good Clinical Practice and approved by the Institutional Review Board (IRB) of Hospital Larcade of San Miguel County (Province of Buenos AIres (Project msm001) inter-rater reproducibility will be evaluated by two raters which will repeatedly apply OASS, OAS and RSS to patients admitted to the emergency room before the study until the intraclass correlation coefficient (ICC) reach a score of 0.80 or greater medications will be packaged in identical color-coded boxes and dosage of of olanzapine and ketiamine will be determined according to standard protocols and previous studies.

If a subject needs another intervention will be removed from the study. subjects will be assessed from 1 to 12 hours after administration of selected medication.

psychiatrists will be masked to patient's treatment assignment, and patients will be instructed not to reveal current treatment to investigators.

clinical safety of treatment will be assessed by notification and with an close-ended inquiry into adverse events together with full physical examination and vital signs measurements. Statistical analyses mean and standard deviation (SD) and comparisons of baseline demographic and clinical characteristics with one-way analysis of variance (ANOVA), chi-square test for categorical variables and mixed-effect analyses of covariance (ANCOVAs) with medication (olanzapine, ketiamine) as between-groups factor and time (1 hour, 2 hours, 4 hours, 6 hours and 12 hours) as a within-group factor. OASS at time zero, OAS at time zero, and presence of excessive sedation will be fixe covariates, and symptom ratings (OASS, OAS and RSS) will be time-varying covariates.

differences between groups at each time point and variance with post-hoc Duncan's tests will be calculated to compare mean OASS, OAS and RSS scores between groups.

Eligibility criteria: Inclusion Criteria:

* signs of agitation,
* age between 18 and 64 years,
* bipolar (maniac or mixed episode)
* psychotic disorder diagnosis
* disorders due to drug abuse,
* organic disorder,
* anxiety or personality disorder
* Overt Agitation Severity Scale Total Score (OASS) equal or greater than 20
* Overt Aggressive Scale (OAS) with four or more positive items.

Exclusion Criteria:

* failure to agree to participate in the study,
* incapability of completing all steps
* unstable clinical disease -
* pregnancy

Primary outcomes:
measure: sedation status
timeFrame: 1 to 12 hours
Secondary outcomes:
measure: adverse effects
timeFrame: 1 to 24 hours
Other outcomes:
Locations:
city: San Miguel
country: Argentina
facility: hospital Larcade
state: Buenos Aires
Study officials:
References: