- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00797277
Intramuscular (IM) Olanzapine Versus IM Haloperidol Plus Lorazepam for Acute Agitation in Schizophrenia
An Open-label, Randomized Trial of Intramuscular (IM) Olanzapine Versus Intramuscular Combination of Haloperidol and Lorazepam in the Treatment of Acute Agitation in Schizophrenia
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Taipei, Taiwan, 100
- Department of Psychiatry, National Taiwan University Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: IM olanzapine
Patients of this arm received 10 mg IM olanzapine after randomization
|
10mg olanzapine IM
Other Names:
|
Active Comparator: IM haloperidol plus lorazepam
Patients of this arm received 5 mg IM haloperidol plus 2 mg IM lorazepam after randomization
|
IM 5 mg haloperidol plus IM 2 mg lorazepam
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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.
|
from baseline to 120 minutes after first injection
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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.
|
from baseline to 120 minutes after first injection
|
Collaborators and Investigators
Collaborators
Investigators
- Study Director: Tzung-Jeng Hwang, MD, MPH, PhD, Department of Psychiatry, National Taiwan University Hospital
Publications and helpful links
General 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. doi: 10.1001/archpsyc.59.5.441.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Schizophrenia Spectrum and Other Psychotic Disorders
- Dyskinesias
- Psychomotor Disorders
- Schizophrenia
- Psychotic Disorders
- Psychomotor Agitation
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiemetics
- Gastrointestinal Agents
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Dopamine Agents
- Dopamine Antagonists
- Hypnotics and Sedatives
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Anticonvulsants
- Anti-Dyskinesia Agents
- Olanzapine
- Haloperidol
- Haloperidol decanoate
- Lorazepam
Other Study ID Numbers
- 950107
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Schizophrenia
-
Organon and CoCompletedSchizophrenia, Paranoid | Schizophrenia, Disorganized | Schizophrenia, Undifferentiated
-
Organon and CoCompletedSchizophrenia, Paranoid | Schizophrenia, Disorganized | Schizophrenia, Undifferentiated
-
Bradley LegaRecruiting
-
All India Institute of Medical Sciences, BhubaneswarRecruitingTreatment Resistant SchizophreniaIndia
-
King's College LondonSouth London and Maudsley NHS Foundation TrustRecruitingTreatment-resistant Schizophrenia | Healthy Controls | Treatment-responsive SchizophreniaUnited Kingdom
-
University of Sao PauloUnknownRefractory Schizophrenia | Super Refractory SchizophreniaBrazil
-
Ohio State UniversityRecruitingTreatment-resistant SchizophreniaUnited States
-
University Hospital, BrestRecruitingSchizophrenia | Schizophrenia Prodromal | Schizophrenia, ChildhoodFrance
-
NYU Langone HealthNot yet recruitingTreatment-resistant SchizophreniaUnited States
-
Johns Hopkins UniversityNational Institute of Mental Health (NIMH)RecruitingTreatment-resistant SchizophreniaUnited States
Clinical Trials on IM olanzapine
-
University of Illinois at ChicagoCompletedIntensity Modulated Total Marrow Irradiation (IM-TMI) for Advanced Hematologic Malignancies (IM-TMI)Acute Myeloid Leukemia | Chronic Myeloid Leukemia | Acute Leukemia | Lymphoblastic Leukemia | Non Hodgkins LymphomaUnited States
-
Fundación Eduardo AnituaRecruiting
-
University Hospitals, LeicesterPublic Health England; Crucell Holland BV; National Institute of Biological Standards...Completed
-
CurvaFix, Inc.RecruitingPelvic Fracture | Acetabular Fracture | Pelvic Ring Fracture | Pelvic Fracture AcetabulumUnited States
-
AstraZenecaCompletedHealthy Volunteer | Coronavirus Disease 2019 (COVID-19)China
-
US Department of Veterans AffairsWithdrawn
-
Children's Fractures Interest Group, DenmarkRecruitingChild, Only | Implant Complication | Forearm Fracture | Fracture Healing | Fracture Fixation, IntramedullaryDenmark
-
Stryker Japan K.K.Unknown
-
Centers for Disease Control and PreventionInternational Centre for Diarrhoeal Disease Research, BangladeshTerminated
-
University of SydneyTelethon Kids Institute; Bionet Co., Ltd; Technovalia; Institute for Clinical Pathology...CompletedSARS-CoV2 COVID-19Australia