Intramuscular (IM) Olanzapine Versus IM Haloperidol Plus Lorazepam for Acute Agitation in Schizophrenia

This study has been completed.
Sponsor:
Collaborator:
Yu-Li Hospital
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00797277
First received: November 24, 2008
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

The aim of this study was to compare the efficacy and safety of intramuscular 10 mg olanzapine versus intramuscular 5 mg haloperidol plus lorazepam 2 mg in the treatment of acute agitated schizophrenic patients of Taiwanese populations.


Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Agitation
Drug: IM olanzapine
Drug: IM haloperidol plus lorazepam
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Randomized Trial of Intramuscular (IM) Olanzapine Versus Intramuscular Combination of Haloperidol and Lorazepam in the Treatment of Acute Agitation in Schizophrenia

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • The Change of the Positive and Negative Symptom Scale Excited Component (PANSS-EC) Score From Baseline to 120 Minutes After First Injection [ Time Frame: from baseline to 120 minutes after first injection ] [ Designated as safety issue: No ]
    The primary efficacy measure was PANSS-EC, which was derived from the PANSS by its originators using a principal-components factor analysis, and includes the items of tension, uncooperativeness, hostility, poor impulse control and excitement.22 The score of each item ranges from 1 (normal) to 7 (most severe), with a total sum score ranging from 5 to 35. The changes in PANSS-EC from baseline to 2 hours after the first injection were compared.


Secondary Outcome Measures:
  • Change of the Agitation-Calmness Evaluation Scale (ACES) Score From Baseline to 120 Minutes After 1st Injection [ Time Frame: from baseline to 120 minutes after first injection ] [ Designated as safety issue: Yes ]
    Agitation was further assessed by the Agitation Calmness Evaluation Scale (ACES) (Copyright 1998, Eli Lilly and Company), a single-item scale developed by Eli Lilly and Company on which 1 indicates marked agitation; 2, moderate agitation; 3, mild agitation; 4, normal; 5, mild calmness; 6, moderate calmness; 7, marked calmness; 8, deep sleep; and 9, unable to be aroused.


Enrollment: 67
Study Start Date: July 2006
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IM olanzapine
Patients of this arm received 10 mg IM olanzapine after randomization
Drug: IM olanzapine
10mg olanzapine IM
Other Name: zyprexa
Active Comparator: IM haloperidol plus lorazepam
Patients of this arm received 5 mg IM haloperidol plus 2 mg IM lorazepam after randomization
Drug: IM haloperidol plus lorazepam
IM 5 mg haloperidol plus IM 2 mg lorazepam
Other Name: haldol and ativan

Detailed Description:

To date, there have been no published reports of clinical studies of IM olanzapine versus IM haloperidol plus lorazepam in acute schizophrenia patients with moderate to severe degree of agitation. The latter combination of treatment is used quite often as a traditional way to treat agitated schizophrenia patients.

Study Design:

This is a randomized, active-controlled, parallel-group study, consisting of screening and treatment phase. Patients completing the screening phase would be randomized to receive either 10mg olanzapine IM or 5 mg haloperidol plus 2 mg lorazepam IM . The ratio of randomization was 1:1. Treatment assignments are based on a computer-generated randomization code supplied by central unit with block designs. Patients can receive a maximum of 3 injections within the first 24-hour period. Second and third injections are used under the clinical judgment of investigators. The second injection is allowed after 2-hour has elapsed since first injection. The third injection is allowed after 4-hour have passed since the second injection. Prohibited medications include antiarrythmics, antipsychotics, antidepressants, anticonvulsants, antiemetics, and other psychotropic drugs.

Efficacy Assessments:

Patients are assessed by the study investigators at the screening visit and at 15, 30, 60, 120 minutes after first injection. The primary efficacy measure is PANSS-EC, which includes the items tension, uncooperativeness, hostility, poor impulse control, excitement and is derived from the PANSS by its originators using a principal-components factor analysis. Agitation is further assessed by the Agitation-Calmness Evaluation Scale (ACES) (Copyright 1998, Eli Lilly and Company; all rights reserved). Clinical Global Impression-Severity(CGI-S)scale37 is used to assess general psychiatric condition. For each patient, the same rater conducted the assessment throughout the study.

Safety assessments:

During the 24-hour treatment period, safety is assessed by clinical examination and laboratory investigations, recording spontaneously reported adverse events, completing the Simpson-Angus Scale (SAS) and Barnes Akathisia Scales (BAS).

Statistical Procedures:

The efficacy analyses were based on intent to treat (ITT) population defined as consisting of all randomized subjects. The last observation carried forward (LOCF) dataset was used to estimate the missing data. Data were analysed using statistical program R Language version 2.8.0 (http://www.r-project.org/), with significance set at p < .05. Demographic characteristics and clinical parameters at baseline were compared by treatment group using the t-test for continuous variables and chi-square test for categorical variables. The primary treatment comparison was 2-hour PANSS-EC scores after first injection. Continuous efficacy and safety data were evaluated by multiple linear regression, adjusting for treatment group, center, and treatment-by-center interaction. The treatment-by-center interaction was tested at the 0.10 significant levels and dropped from the model if it was not statistically significant. To compare the number difference in adverse events between two treatment groups, Fisher's exact test was used due to low cell counts.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and non-pregnant, non-lactating women aged 18 to 65 years with a primary diagnosis of schizophrenia (DSM-IV)
  • were hospitalized due to an acute relapse
  • were clinically agitated with a minimum total score of ≧ 14 on the five items of the PANSS-EC and at least one individual item score of ≧ 4 using the 1-7 scoring system prior to first IM injection of study drug.

Exclusion Criteria:

  • female subjects who were either pregnant or breast-feeding;
  • patients with acute, serious or unstable medical conditions;
  • treatment with benzodiazepines within 4 hours prior to the first IM study drug administration;
  • treatment with an injection depot neuroleptic within 1 injection interval prior to study drug administration;
  • history of allergic reaction or intolerance to study medication(s);
  • had a known diagnosis of dementia of any type, as defined in the DSM-IV.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00797277

Locations
Taiwan
Department of Psychiatry, National Taiwan University Hospital
Taipei, Taiwan, 100
Sponsors and Collaborators
National Taiwan University Hospital
Yu-Li Hospital
Investigators
Study Director: Tzung-Jeng Hwang, MD, MPH, PhD Department of Psychiatry, National Taiwan University Hospital
  More Information

Publications:
Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT00797277     History of Changes
Other Study ID Numbers: 950107
Study First Received: November 24, 2008
Results First Received: August 12, 2013
Last Updated: September 11, 2014
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
schizophrenia
schizoaffective disorder
olanzapine
haloperidol
lorazepam
agitation

Additional relevant MeSH terms:
Psychomotor Agitation
Psychotic Disorders
Schizophrenia
Dyskinesias
Mental Disorders
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Psychomotor Disorders
Schizophrenia and Disorders with Psychotic Features
Signs and Symptoms
Haloperidol
Haloperidol decanoate
Lorazepam
Olanzapine
Anti-Anxiety Agents
Anti-Dyskinesia Agents
Anticonvulsants
Antiemetics
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
GABA Agents
GABA Modulators
Gastrointestinal Agents
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 29, 2014