Pragmatic RCT Comparing Aripiprazole, Olanzapine and Haloperidol in the Treatment of Schizophrenia - Full Text View

Purpose

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.

Condition	Intervention	Phase
Schizophrenia	Drug: Aripiprazole Drug: Olanzapine Drug: Haloperidol	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	GiSAS Trial: Aripiprazole, Olanzapine, and Haloperidol in the Long Term Treatment of Schizophrenia.

Resource links provided by NLM:

Genetics Home Reference related topics: schizophrenia

MedlinePlus related topics: Schizophrenia

Drug Information available for: Haloperidol Haloperidol decanoate Aripiprazole Olanzapine Olanzapine pamoate

U.S. FDA Resources

Further study details as provided by Mario Negri Institute for Pharmacological Research:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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
Global functioning and symptomatology (GAF) [ Time Frame: 12 months. ] [ Designated as safety issue: No ]
Time to discontinuation due to efficacy [ Time Frame: 12 months. ] [ Designated as safety issue: No ]
Time to discontinuation due to side effects [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Worsening of metabolic profile [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Defined as the onset of at least one metabolic syndrome criterion; onset of serum lipids abnormalities (dyslipidemia)
Neuroleptic side effects' self-rating (LUNSERS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]


Enrollment:	300
Study Start Date:	July 2007
Study Completion Date:	June 2013
Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Aripiprazole Aripiprazole (N05AX12)	Drug: Aripiprazole 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. Other Name: ATC code: N05AX12
Experimental: Olanzapine Olanzapine (N05AH03)	Drug: Olanzapine 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. Other Name: ATC code: N05AH03
Experimental: Haloperidol Haloperidol (N05AD01)	Drug: Haloperidol 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). Other Name: ATC code: N05AD01

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Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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).

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01052389

Locations


Italy
Department of Mental Health
Genoa, Liguria, Italy, 16125

Sponsors and Collaborators

Mario Negri Institute for Pharmacological Research

Bristol-Myers Squibb

Investigators


Principal Investigator:	Angelo Barbato, M.D.	'Mario Negri' Institute for Pharmacological Research
Study Director:	Alberto Parabiaghi, M.D.	'Mario Negri' Institute for Pharmacological Research
Study Chair:	Barbara D'Avanzo, Phil.D.	'Mario Negri' Institute for Pharmacological Research
Study Chair:	Mauro Tettamanti, Biol.D.	'Mario Negri' Institute for Pharmacological Research

More Information

Additional Information:

GiSAS Study This link exits the ClinicalTrials.gov site

UE Clinical Trials Register This link exits the ClinicalTrials.gov site

IRCCS 'Mario Negri' Institute for Pharmacological Research This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ghio 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.

Parabiaghi 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.


Responsible Party:	Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier:	NCT01052389 History of Changes
Other Study ID Numbers:	GiSAS 001 2007-000278-22
Study First Received:	January 18, 2010
Last Updated:	April 9, 2014
Health Authority:	Italy: The Italian Medicines Agency European Union: European Medicines Agency

Keywords provided by Mario Negri Institute for Pharmacological Research:


Schizophrenia Pragmatic RCT Aripiprazole Olanzapine	Haloperidol Metabolic syndrome Drug discontinuation

Additional relevant MeSH terms:


Schizophrenia Schizophrenia Spectrum and Other Psychotic Disorders Mental Disorders Aripiprazole Olanzapine Haloperidol Haloperidol decanoate Antipsychotic Agents Tranquilizing Agents Central Nervous System Depressants Physiological Effects of Drugs Psychotropic Drugs Antiemetics	Autonomic Agents Peripheral Nervous System Agents Gastrointestinal Agents Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Serotonin Agents Dopamine Antagonists Dopamine Agents Anti-Dyskinesia Agents

ClinicalTrials.gov processed this record on September 27, 2016

Pragmatic RCT Comparing Aripiprazole, Olanzapine and Haloperidol in the Treatment of Schizophrenia (GiSAS)