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

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier:
NCT01052389
First received: January 18, 2010
Last updated: April 9, 2014
Last verified: April 2014
  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:


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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
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
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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:
No publications provided by Mario Negri Institute for Pharmacological Research

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 and Disorders with Psychotic Features
Mental Disorders
Haloperidol
Olanzapine
Haloperidol decanoate
Aripiprazole
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Serotonin Agents

ClinicalTrials.gov processed this record on July 26, 2014