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

NCT01052389 | Completed Phase 4 DMC

• 2 other identifiers: GiSAS 0012007-000278-22
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Schizophrenia

Keywords

Schizophrenia; Pragmatic RCT; Aripiprazole; Olanzapine; Haloperidol; Metabolic syndrome; Drug discontinuation

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  12 months

• Global functioning and symptomatology (GAF)

  12 months.

• Time to discontinuation due to efficacy

  12 months.

• Time to discontinuation due to side effects

  12 months

• Worsening of metabolic profile

  12 months

Study Arms (3)

Aripiprazole

EXPERIMENTAL

Aripiprazole (N05AX12)

Drug: Aripiprazole

Olanzapine

EXPERIMENTAL

Olanzapine (N05AH03)

Drug: Olanzapine

Haloperidol

EXPERIMENTAL

Haloperidol (N05AD01)

Drug: Haloperidol

Interventions

Aripiprazole DRUG

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.

Also known as: ATC code: N05AX12

Aripiprazole

Olanzapine DRUG

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.

Also known as: ATC code: N05AH03

Olanzapine

Haloperidol DRUG

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).

Also known as: ATC code: N05AD01

Haloperidol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Department of Mental Health

Genoa, Liguria, 16125, Italy

Location

Related Publications (3)

• 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.

  PMID: 38958149 DERIVED

• 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.

  PMID: 21710401 DERIVED

• 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.

  PMID: 21554991 DERIVED

Related Links

• GiSAS Study
• UE Clinical Trials Register

MeSH Terms

Conditions

Schizophrenia; Metabolic Syndrome

Interventions

Aripiprazole; Olanzapine; Haloperidol

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzodiazepines; Benzazepines; Butyrophenones; Ketones; Organic Chemicals

Study Officials

• Angelo Barbato, M.D.

  'Mario Negri' Institute for Pharmacological Research

  PRINCIPAL INVESTIGATOR

• Alberto Parabiaghi, M.D.

  'Mario Negri' Institute for Pharmacological Research

  STUDY DIRECTOR

• Barbara D'Avanzo, Phil.D.

  'Mario Negri' Institute for Pharmacological Research

  STUDY CHAIR

• Mauro Tettamanti, Biol.D.

  'Mario Negri' Institute for Pharmacological Research

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2010
• First Posted: January 20, 2010
• Study Start: July 1, 2007
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2013
• Last Updated: April 10, 2014

Record last verified: 2014-04

Locations

IT (1)