SchizophreniaPhase 3NCT00797277
Intramuscular (IM) Olanzapine Versus IM Haloperidol Plus Lorazepam for Acute Agitation in Schizophrenia
A Phase 3 study testing IM olanzapine and IM haloperidol plus lorazepam in people with Schizophrenia and Schizoaffective Disorder, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder, Agitation
- What is being tested?
- IM olanzapine and IM haloperidol plus lorazepam
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 1 siteTaiwan
- Study dates
- Jul 2006to Jun 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
Department of Psychiatry, National Taiwan University Hospital
Taipei, 100
About this study
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
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.
Read the 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
- Being tested
- IM olanzapine, IM haloperidol plus lorazepam
- Keywords
- schizophrenia, schizoaffective disorder, olanzapine, haloperidol, lorazepam, agitation
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Psychomotor Agitation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IM olanzapineDrug
Also called zyprexa
10mg olanzapine IM
IM haloperidol plus lorazepamDrug
Also called haldol and ativan
IM 5 mg haloperidol plus IM 2 mg lorazepam
| Study group | Role | What they receive |
|---|---|---|
| IM olanzapine | Experimental | Patients of this arm received 10 mg IM olanzapine after randomization Receives: Drug: IM olanzapine |
| IM haloperidol plus lorazepam | Active comparator | Patients of this arm received 5 mg IM haloperidol plus 2 mg IM lorazepam after randomization Receives: Drug: IM haloperidol plus lorazepam |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Change of the Positive and Negative Symptom Scale Excited Component (PANSS-EC) Score 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.
Measured: from baseline to 120 minutes after first injection
Secondary outcomes (1)
Change of the Agitation-Calmness Evaluation Scale (ACES) Score From Baseline to 120 Minutes After 1st 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.
Measured: from baseline to 120 minutes after first injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2008 (estimated)
- Study startJul 2006
- Primary completionJun 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Yu-Li Hospital
- Responsible party
- Sponsor
- Investigators
- Tzung-Jeng Hwang, MD, MPH, PhD, Study director, Department of Psychiatry, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00797277
- Sponsor's protocol ID
- 950107
- Status last verified
- Sep 2014
- First submitted
- 24 Nov 2008
- Last updated
- 15 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 11982448Huang 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.
PubMed 25791540
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00797277
- Acronym / sponsor ID
- 950107
- Conditions
- Schizophrenia, Schizoaffective Disorder, Agitation
- Keywords
- schizophrenia, schizoaffective disorder, olanzapine, haloperidol, lorazepam, agitation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Collaborators
- Yu-Li Hospital
- Study start
- Jul 2006
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 25 Nov 2008 (estimated)
- Results
- Posted 15 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IM olanzapine | Experimental | Drug: IM olanzapinePatients of this arm received 10 mg IM olanzapine after randomization |
| IM haloperidol plus lorazepam | Active comparator | Drug: IM haloperidol plus lorazepamPatients of this arm received 5 mg IM haloperidol plus 2 mg IM lorazepam after randomization |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (6 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IM olanzapineAlso: zyprexa10mg olanzapine IM | Drug | IM olanzapine |
| IM haloperidol plus lorazepamAlso: haldol and ativanIM 5 mg haloperidol plus IM 2 mg lorazepam | Drug | IM haloperidol plus lorazepam |
Primary outcome
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.
1 secondary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11982448Breier 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.
- Derived from this study: PubMed 25791540Huang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tzung-Jeng Hwang, MD, MPH, PhD study director
Department of Psychiatry, National Taiwan University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing IM olanzapine and IM haloperidol plus lorazepam in people with Schizophrenia and Schizoaffective Disorder, run by National Taiwan University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00797277, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2014.