SchizophreniaPhase 4GiSASNCT01052389
Pragmatic RCT Comparing Aripiprazole, Olanzapine and Haloperidol in the Treatment of Schizophrenia
A Phase 4 study testing Aripiprazole, Olanzapine and Haloperidol in people with Schizophrenia, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
Trial summary
The GiSAS study is a multi-centre randomized clinical trial that will involve about 80 italian community psychiatric services in Italy and will recruit 800 patients affected by schizophrenia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Aripiprazole, Olanzapine and Haloperidol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteItaly
- Study dates
- Jul 2007to Jun 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- men and women, 18 years of age and over, who meet DSM-IV criteria for schizophrenia, based upon the Mini International Neuropsychiatric Interview;
- patients entering the study must, according to their own judgment in consultation with their physician, have a condition appropriate for (a) starting treatment with an oral antipsychotic medication or (b) changing antipsychotic treatment.
Who cannot join
- diagnosis of metabolic syndrome, defined as the fulfilling of at least 3 of the diagnostic criteria for the metabolic syndrome derived from Adult Treatment Protocol III (ATP III);
- diagnosis of diabetes mellitus type II;
- presence of an organic condition clearly contraindicating treatment with one of the studied drugs, e.g., pregnancy or breast-feeding;
- one of the studied treatments is positively known to be ineffective or not tolerable and consequently contraindicated;
- the patient has never been exposed to antipsychotic drugs;
- according to clinician's opinion, it is unlikely that the patient can be followed for the whole duration of the study (1 year).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: GiSAS Trial: Aripiprazole, Olanzapine, and Haloperidol in the Long Term Treatment of Schizophrenia.
The GiSAS study is a multi-centre randomized clinical trial that will involve about 80 italian community psychiatric services in Italy and will recruit 800 patients affected by schizophrenia.
In a sample of schizophrenic outpatients, it is hypothesized that there are significant differences in the overall tolerability and effectiveness of aripiprazole, olanzapine and haloperidol at 12 months.
Read more
It is a pragmatic trial. Thus, participants are selected to represent a broad range of "real-world" patients, all treatment medications are non-blinded and after randomization, the assigned drugs will be prescribed according to usual care practice.
The measure for effectiveness is retention of patients on the assigned treatment. The measure for tolerability is the onset of metabolic syndrome.
Read the detailed description
Specific aim.
The GiSAS study is a randomized controlled superiority trial that aims to evaluate the tolerability and effectiveness of aripiprazole, olanzapine and haloperidol in outpatients with schizophrenia over a 12-month period.
Inclusion criteria.
- Age≥18.
- Patients entering the study must have a condition appropriate for changing the antipsychotic treatment or starting a new one.
Exclusion criteria.
- Diagnosis of metabolic syndrome.
- Diagnosis of diabetes mellitus type II.
- The patient has never been exposed to antipsychotic drugs.
- One of the studied treatments is clearly contraindicated.
Recruitment.
The study will be conducted in a broad array of clinical settings in order to provide generalizable and practically relevant study findings. The recruitment period will last 12 months in each participating center.
Study design.
The GiSAS study is a multi-centre RCT that will involve about 80 italian psychiatric services and will recruit 800 patients affected by schizophrenia.
In a non-selected sample of schizophrenic patients, it is hypothesized that there are significant differences in the overall safety, tolerability and acceptability of aripiprazole, olanzapine and haloperidol and consequently in their effectiveness.
It is a pragmatic trial. Thus, participants are selected to represent a broad range of "real-world" patients, including those with comorbid conditions (i.e. substance use disorders, medical problems.
Patients will be assessed:
- at baseline (all subjects);
- when monotherapy treatment is stopped;
- at 12 months (all subjects).
Pharmacological treatments.
In this study, the following drugs will be tested: (a) aripiprazole, (b) olanzapine, (c) haloperidol. All treatment medications are non-blinded.
After randomization, the assigned drugs will be prescribed according to usual care practice. Patients will be prescribed daily oral dose of the assigned drug, based on individual response and side-effects. For patients already taking an antipsychotic medication prior to study entry, tapering the previous medication over a period of four weeks will be allowed.
All the drugs used in each arm of GiSAS trial are currently licensed and marketed in Italy for the treatment of schizophrenia. No other antipsychotic medication will be allowed.
Concomitant psychotropic medication (e.g. benzodiazepines, antidepressants) and the use of non-psychotropic drugs will be allowed and routinely recorded.
Primary outcomes.
The measure for effectiveness is retention of patients on the assigned treatment at 12 months. The measure for tolerability is the onset of metabolic syndrome at 12 months (primary endpoint). Switching to another antipsychotic, adding a second antipsychotic or stopping antipsychotic treatment will be considered as drug discontinuation. Reasons for discontinuation will be registered and will be taken into account when creating the secondary outcomes.
In order to capture whether, when and why participants stop the assigned treatment or add concomitant medication, the patients' ongoing treatments will be monitored at least once a month.
The primary endpoint (i.e. Metabolic Syndrome) is assessed centrally by blinded independent observers.
All statistical analyses will be blinded and will include all randomized subjects following the intent-to-treat principle.
- Conditions
- Schizophrenia
- Being tested
- Aripiprazole, Olanzapine, Haloperidol
- Keywords
- Schizophrenia, Pragmatic RCT, Aripiprazole, Olanzapine, Haloperidol, Metabolic syndrome, Drug discontinuation
- Medical subject headings
- Schizophrenia, Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AripiprazoleDrug
Also called ATC code: N05AX12
Patients allocated to aripiprazole will be prescribed daily oral dose of drug, based on individual response and side-effects. Suggested starting dose will be 10 mg/day and dose range will be 10-30 mg/day.
OlanzapineDrug
Also called ATC code: N05AH03
Patients allocated to olanzapine will be prescribed daily oral dose of drug, based on individual patients' response and side-effect burden. Suggested starting dose will be 5 mg/day and dose range will be 10-20 mg/day.
HaloperidolDrug
Also called ATC code: N05AD01
Patients allocated to haloperidol FGA arm will be prescribed daily oral dose of drug, based on individual patients' response and side-effect burden.
Suggested starting dose will be 1-3 mg/day and dose range 3-10 mg/day (chlorpromazine equivalents: suggested starting dose 50-100 mg/day; dose range 150-300 mg/day).
| Study group | Role | What they receive |
|---|---|---|
| Aripiprazole | Experimental | Aripiprazole (N05AX12) Receives: Drug: Aripiprazole |
| Olanzapine | Experimental | Olanzapine (N05AH03) Receives: Drug: Olanzapine |
| Haloperidol | Experimental | Haloperidol (N05AD01) Receives: Drug: Haloperidol |
What is being measured
The primary outcome is the main question the study is designed to answer.
The measure for tolerability is the onset of metabolic syndrome as defined by meeting at least 3 of the following criteria: (1) abdominal obesity, (2) high triglycerides, (3) high HDL, (4) high blood pressure and (5) hyperglycaemia.
Measured: 12 months
Secondary outcomes (6)
The primary measure for effectiveness is retention of patients on the assigned treatment at 12 months. Switching to another antipsychotic, adding a second antipsychotic or stopping antipsychotic treatment will be considered as drug discontinuation.
The trial takes account of two main outcomes, one for tolerability and one for effectiveness. Together, in fact, they must provide the most clinically relevant and convincing evidence directly related to the primary objective of the trial. The proportion of subjects who developed MS at one year was compared between the study groups and was adopted as primary endpoint. However, as the study design and conduction were focused on the one-year retention of the allocated monotherapy, the study power was estimated for this secondary endpoint too
Measured: 12 months
Global functioning and symptomatology (GAF)
Measured: 12 months.
Time to discontinuation due to efficacy
Measured: 12 months.
Time to discontinuation due to side effects
Measured: 12 months
Worsening of metabolic profile
Defined as the onset of at least one metabolic syndrome criterion; onset of serum lipids abnormalities (dyslipidemia)
Measured: 12 months
Neuroleptic side effects' self-rating (LUNSERS)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2010 (estimated)
- Study startJul 2007
- Primary completionJun 2012
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Mario Negri Institute for Pharmacological ResearchThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Angelo Barbato, M.D., Principal investigator, 'Mario Negri' Institute for Pharmacological ResearchAlberto Parabiaghi, M.D., Study director, 'Mario Negri' Institute for Pharmacological ResearchBarbara D'Avanzo, Phil.D., Study chair, 'Mario Negri' Institute for Pharmacological ResearchMauro Tettamanti, Biol.D., Study chair, 'Mario Negri' Institute for Pharmacological Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01052389
- Sponsor's protocol ID
- GiSAS 001
- Other IDs
- 2007-000278-22
- Acronym
- GiSAS
- Status last verified
- Apr 2014
- First submitted
- 18 Jan 2010
- Last updated
- 10 Apr 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ibragimov K, Keane GP, Carreno Glaria C, Cheng J, Llosa AE. Haloperidol (oral) versus olanzapine (oral) for people with schizophrenia and schizophrenia-spectrum disorders. Cochrane Database Syst Rev. 2024 Jul 3;7(7):CD013425. doi: 10.1002/14651858.CD013425.pub2.
PubMed 38958149Ghio L, Natta W, Barbato A, Marcenaro M, Gotelli S, Jones PB, Parabiaghi A. Schizophrenia trial participation: perceived inclusion barriers and beliefs about antipsychotics. Pharmacopsychiatry. 2011 Jun;44(4):123-8. doi: 10.1055/s-0031-1277147. Epub 2011 Jun 27.
PubMed 21710401Parabiaghi A, D'Avanzo B, Tettamanti M, Barbato A; GiSAS Study Group. The GiSAS study: rationale and design of a pragmatic randomized controlled trial on aripiprazole, olanzapine and haloperidol in the long-term treatment of schizophrenia. Contemp Clin Trials. 2011 Sep;32(5):675-84. doi: 10.1016/j.cct.2011.04.008. Epub 2011 Apr 30.
PubMed 21554991
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GiSAS Trial: Aripiprazole, Olanzapine, and Haloperidol in the Long Term Treatment of Schizophrenia.
- ClinicalTrials.gov ID
- NCT01052389
- Acronym / sponsor ID
- GiSAS / GiSAS 001
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, Pragmatic RCT, Aripiprazole, Olanzapine, Haloperidol, Metabolic syndrome, Drug discontinuation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Jul 2007
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 20 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The GiSAS study is a multi-centre randomized clinical trial that will involve about 80 italian community psychiatric services in Italy and will recruit 800 patients affected by schizophrenia.
In a sample of schizophrenic outpatients, it is hypothesized that there are significant differences in the overall tolerability and effectiveness of aripiprazole, olanzapine and haloperidol at 12 months.
It is a pragmatic trial. Thus, participants are selected to represent a broad range of "real-world" patients, all treatment medications are non-blinded and after randomization, the assigned drugs will be prescribed according to usual care practice.
The measure for effectiveness is retention of patients on the assigned treatment. The measure for tolerability is the onset of metabolic syndrome.
Detailed description
Specific aim.
The GiSAS study is a randomized controlled superiority trial that aims to evaluate the tolerability and effectiveness of aripiprazole, olanzapine and haloperidol in outpatients with schizophrenia over a 12-month period.
Inclusion criteria.
- Age≥18.
- Patients entering the study must have a condition appropriate for changing the antipsychotic treatment or starting a new one.
Exclusion criteria.
- Diagnosis of metabolic syndrome.
- Diagnosis of diabetes mellitus type II.
- The patient has never been exposed to antipsychotic drugs.
- One of the studied treatments is clearly contraindicated.
Recruitment.
The study will be conducted in a broad array of clinical settings in order to provide generalizable and practically relevant study findings. The recruitment period will last 12 months in each participating center.
Study design.
The GiSAS study is a multi-centre RCT that will involve about 80 italian psychiatric services and will recruit 800 patients affected by schizophrenia.
In a non-selected sample of schizophrenic patients, it is hypothesized that there are significant differences in the overall safety, tolerability and acceptability of aripiprazole, olanzapine and haloperidol and consequently in their effectiveness.
It is a pragmatic trial. Thus, participants are selected to represent a broad range of "real-world" patients, including those with comorbid conditions (i.e. substance use disorders, medical problems.
Patients will be assessed:
- at baseline (all subjects);
- when monotherapy treatment is stopped;
- at 12 months (all subjects).
Pharmacological treatments.
In this study, the following drugs will be tested: (a) aripiprazole, (b) olanzapine, (c) haloperidol. All treatment medications are non-blinded.
After randomization, the assigned drugs will be prescribed according to usual care practice. Patients will be prescribed daily oral dose of the assigned drug, based on individual response and side-effects. For patients already taking an antipsychotic medication prior to study entry, tapering the previous medication over a period of four weeks will be allowed.
All the drugs used in each arm of GiSAS trial are currently licensed and marketed in Italy for the treatment of schizophrenia. No other antipsychotic medication will be allowed.
Concomitant psychotropic medication (e.g. benzodiazepines, antidepressants) and the use of non-psychotropic drugs will be allowed and routinely recorded.
Primary outcomes.
The measure for effectiveness is retention of patients on the assigned treatment at 12 months. The measure for tolerability is the onset of metabolic syndrome at 12 months (primary endpoint). Switching to another antipsychotic, adding a second antipsychotic or stopping antipsychotic treatment will be considered as drug discontinuation. Reasons for discontinuation will be registered and will be taken into account when creating the secondary outcomes.
In order to capture whether, when and why participants stop the assigned treatment or add concomitant medication, the patients' ongoing treatments will be monitored at least once a month.
The primary endpoint (i.e. Metabolic Syndrome) is assessed centrally by blinded independent observers.
All statistical analyses will be blinded and will include all randomized subjects following the intent-to-treat principle.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Aripiprazole | Experimental | Drug: AripiprazoleAripiprazole (N05AX12) |
| Olanzapine | Experimental | Drug: OlanzapineOlanzapine (N05AH03) |
| Haloperidol | Experimental | Drug: HaloperidolHaloperidol (N05AD01) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- men and women, 18 years of age and over, who meet DSM-IV criteria for schizophrenia, based upon the Mini International Neuropsychiatric Interview;
- patients entering the study must, according to their own judgment in consultation with their physician, have a condition appropriate for (a) starting treatment with an oral antipsychotic medication or (b) changing antipsychotic treatment.
Key exclusion criteria (6 listed)
- diagnosis of metabolic syndrome, defined as the fulfilling of at least 3 of the diagnostic criteria for the metabolic syndrome derived from Adult Treatment Protocol III (ATP III);
- diagnosis of diabetes mellitus type II;
- presence of an organic condition clearly contraindicating treatment with one of the studied drugs, e.g., pregnancy or breast-feeding;
- one of the studied treatments is positively known to be ineffective or not tolerable and consequently contraindicated;
- the patient has never been exposed to antipsychotic drugs;
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 |
|---|---|---|
| AripiprazoleAlso: ATC code: N05AX12Patients allocated to aripiprazole will be prescribed daily oral dose of drug, based on individual response and side-effects. Suggested starting dose will be 10 mg/day and dose range will be 10-30 mg/day. | Drug | Aripiprazole |
| OlanzapineAlso: ATC code: N05AH03Patients allocated to olanzapine will be prescribed daily oral dose of drug, based on individual patients' response and side-effect burden. Suggested starting dose will be 5 mg/day and dose range will be 10-20 mg/day. | Drug | Olanzapine |
| HaloperidolAlso: ATC code: N05AD01Patients allocated to haloperidol FGA arm will be prescribed daily oral dose of drug, based on individual patients' response and side-effect burden. Suggested starting dose will be 1-3 mg/day and dose range 3-10 mg/day (chlorpromazine equivalents: suggested starting dose 50-100 mg/day; dose range 150-300 mg/day). | Drug | Haloperidol |
Primary outcome
The measure for tolerability is the onset of metabolic syndrome as defined by meeting at least 3 of the following criteria: (1) abdominal obesity, (2) high triglycerides, (3) high HDL, (4) high blood pressure and (5) hyperglycaemia.
Time frame: 12 months
6 secondary outcomes
The primary measure for effectiveness is retention of patients on the assigned treatment at 12 months. Switching to another antipsychotic, adding a second antipsychotic or stopping antipsychotic treatment will be considered as drug discontinuation.
Time frame: 12 months
Global functioning and symptomatology (GAF)
Time frame: 12 months.
Time to discontinuation due to efficacy
Time frame: 12 months.
Time to discontinuation due to side effects
Time frame: 12 months
Worsening of metabolic profile
Time frame: 12 months
Neuroleptic side effects' self-rating (LUNSERS)
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2014.
- Derived from this study: PubMed 38958149Ibragimov K, Keane GP, Carreno Glaria C, Cheng J, Llosa AE. Haloperidol (oral) versus olanzapine (oral) for people with schizophrenia and schizophrenia-spectrum disorders. Cochrane Database Syst Rev. 2024 Jul 3;7(7):CD013425. doi: 10.1002/14651858.CD013425.pub2.
- Derived from this study: PubMed 21710401Ghio L, Natta W, Barbato A, Marcenaro M, Gotelli S, Jones PB, Parabiaghi A. Schizophrenia trial participation: perceived inclusion barriers and beliefs about antipsychotics. Pharmacopsychiatry. 2011 Jun;44(4):123-8. doi: 10.1055/s-0031-1277147. Epub 2011 Jun 27.
- Derived from this study: PubMed 21554991Parabiaghi A, D'Avanzo B, Tettamanti M, Barbato A; GiSAS Study Group. The GiSAS study: rationale and design of a pragmatic randomized controlled trial on aripiprazole, olanzapine and haloperidol in the long-term treatment of schizophrenia. Contemp Clin Trials. 2011 Sep;32(5):675-84. doi: 10.1016/j.cct.2011.04.008. Epub 2011 Apr 30.
- UE Clinical Trials RegisterLink provided by the sponsor.
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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.
Angelo Barbato, M.D. principal investigator
'Mario Negri' Institute for Pharmacological Research
Alberto Parabiaghi, M.D. study director
'Mario Negri' Institute for Pharmacological Research
Barbara D'Avanzo, Phil.D. study chair
'Mario Negri' Institute for Pharmacological Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Aripiprazole, Olanzapine and Haloperidol in people with Schizophrenia, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
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 2 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 10 Apr 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 Italy. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 measure for tolerability is the onset of metabolic syndrome as defined by meeting at least 3 of the following criteria: (1) abdominal obesity, (2) high triglycerides, (3) high HDL, (4) high blood pressure and (5) hyperglycaemia. (time frame: 12 months). 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 NCT01052389, which also lists 3 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 10 Apr 2014.