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

Condition(s) targeted: Schizophrenia; Schizoaffective Disorder; Agitation

Intervention: IM olanzapine (Drug); haloperidol plus lorazepam IM (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: National Taiwan University Hospital

Official(s) and/or principal investigator(s):
Tzung-Jeng Hwang, MD, Study Director, Affiliation: Department of Psychiatry, National Taiwan University Hospital

Overall contact:
Tzung-Jeng Hwang, MD, Phone: 886-2-23123456, Ext: 66792, Email: tjhwang@ntu.edu.tw

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.

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

Study design: Treatment, Randomized, Single Blind (Subject), Active Control, Parallel Assignment, Efficacy Study

Primary outcome: Positive and Negative Symptom Scale Excited Component (PANSS-EC)

Secondary outcome: Agitation-Calmness Evaluation Scale (ACES)

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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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.

Tzung-Jeng Hwang, MD, Phone: 886-2-23123456, Ext: 66792, Email: tjhwang@ntu.edu.tw

Department of Psychiatry, National Taiwan University Hospital, Taipei 100, Taiwan; Recruiting
Tzung-Jeng Hwang, MD, Phone: +886-2-23123456, Ext: 66792, Email: tjhwang@ntu.edu.tw

Related publications:

Breier A, Meehan K, Birkett M, David S, Ferchland I, Sutton V, Taylor CC, Palmer R, Dossenbach M, Kiesler G, Brook S, Wright P. A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia. Arch Gen Psychiatry. 2002 May;59(5):441-8.

Starting date: July 2006
Ending date: February 2009
Last updated: November 24, 2008