IM Olanzapine Versus IM Haloperidol Plus Lorazepam for Acute Agitation in Schizophrenia

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2008 by National Taiwan University Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Yu-Li Hospital
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00797277
First received: November 24, 2008
Last updated: NA
Last verified: November 2008
History: No changes posted
  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: haloperidol plus lorazepam IM
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: An Open-Label, Randomized Trial of Intramuscular 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:
  • Positive and Negative Symptom Scale Excited Component (PANSS-EC) [ Time Frame: 15, 30, 60, 120 minutes after first injection ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Agitation-Calmness Evaluation Scale (ACES) [ Time Frame: 15, 30, 60, 120 minutes after first injection ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: July 2006
Estimated Study Completion Date: February 2009
Estimated Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1. IM olanzapine Drug: IM olanzapine
10mg olanzapine IM
Other Name: zyprexa
Active Comparator: 2. IM haloperidol pus lorazepam Drug: haloperidol plus lorazepam IM
5 mg haloperidol plus 2 mg lorazepam, IM
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 patients with schizophrenia. The latter combination is used quite often as a traditional way to treat agitated schizophrenia patients.

Study Design:

This is a randomized, single-blind, 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 (SAS3) and Barnes Akathisia Scales (BAS).

Statistical Procedures:

The efficacy analyses are based on intent-to treat (ITT) population defined as consisting of all randomized subjects. The last observation carried forward (LOCF) dataset is used to estimate the missing data. The primary treatment comparisons are 2-hour PANSS-EC scores after first injection. Continuous efficacy data (eg, change from baseline) are evaluated by analysis of covariance (ANCOVA), adjusting for baseline values and the fixed factors treatment, 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. The 95% confidence interval is used to provide the test of hypothesis of efficacy of olanzapine is superior to haloperidol plus lorazepam. Categorical efficacy data are analysed using the Cochran-Mantel-Haenszel test with center control. For primary efficacy analyses, the hypothesis was one-sided and evaluated at the 0.025 significant levels. For other analyses, the test was two-sided and evaluated at the 0.05 significant levels.

Response is defined a priori as a 40% reduction or more in PANSS-EC scores. Response rate is also analysed using the Cochran-Mantel-Haenszel test with center control, and the Breslow-Day test to investigate the homogeneity of odds ratio across sites.

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00797277

Contacts
Contact: Tzung-Jeng Hwang, MD 886-2-23123456 ext 66792 tjhwang@ntu.edu.tw

Locations
Taiwan
Department of Psychiatry, National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Tzung-Jeng Hwang, MD    +886-2-23123456 ext 66792    tjhwang@ntu.edu.tw   
Sponsors and Collaborators
National Taiwan University Hospital
Yu-Li Hospital
Investigators
Study Director: Tzung-Jeng Hwang, MD Department of Psychiatry, National Taiwan University Hospital
  More Information

Publications:
Responsible Party: Tzung-Jeng Hwang, MD, National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT00797277     History of Changes
Other Study ID Numbers: 950107
Study First Received: November 24, 2008
Last Updated: November 24, 2008
Health Authority: Taiwan: Department of Health

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

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Psychomotor Agitation
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Psychomotor Disorders
Neurobehavioral Manifestations
Signs and Symptoms
Haloperidol
Lorazepam
Olanzapine
Haloperidol decanoate
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on July 22, 2014