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

NCT ID: NCT00797277

Last Updated: 2014-09-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-31
• Study Completion Date: 2009-06-30

Brief Summary

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.

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.

Conditions

Schizophrenia; Schizoaffective Disorder; Agitation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IM olanzapine

Patients of this arm received 10 mg IM olanzapine after randomization

Group Type: EXPERIMENTAL

IM olanzapine

Intervention Type: DRUG

10mg olanzapine IM

IM haloperidol plus lorazepam

Patients of this arm received 5 mg IM haloperidol plus 2 mg IM lorazepam after randomization

Group Type: ACTIVE_COMPARATOR

IM haloperidol plus lorazepam

Intervention Type: DRUG

IM 5 mg haloperidol plus IM 2 mg lorazepam

Interventions

IM olanzapine

10mg olanzapine IM

Intervention Type: DRUG

IM haloperidol plus lorazepam

IM 5 mg haloperidol plus IM 2 mg lorazepam

Intervention Type: DRUG

Other Intervention Names

zyprexa; haldol and ativan

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yu-Li Hospital

OTHER

Sponsor Role: collaborator

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tzung-Jeng Hwang, MD, MPH, PhD

Role: STUDY_DIRECTOR

Department of Psychiatry, National Taiwan University Hospital

Locations

Department of Psychiatry, National Taiwan University Hospital

Taipei, , Taiwan

Countries

Taiwan

References

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. doi: 10.1001/archpsyc.59.5.441.

Reference Type: BACKGROUND

PMID: 11982448 (View on PubMed)

Huang CL, Hwang TJ, Chen YH, Huang GH, Hsieh MH, Chen HH, Hwu HG. Intramuscular olanzapine versus intramuscular haloperidol plus lorazepam for the treatment of acute schizophrenia with agitation: An open-label, randomized controlled trial. J Formos Med Assoc. 2015 May;114(5):438-45. doi: 10.1016/j.jfma.2015.01.018. Epub 2015 Mar 17.

Reference Type: DERIVED

PMID: 25791540 (View on PubMed)

Other Identifiers

950107

Identifier Type: -

Identifier Source: org_study_id