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Trial registered on ANZCTR


Registration number
ACTRN12610000954022
Ethics application status
Approved
Date submitted
2/11/2010
Date registered
8/11/2010
Date last updated
8/11/2010
Type of registration
Retrospectively registered

Titles & IDs
Public title
An open randomised clinical trial involving Haloperidol, Olanzapine, Quetiapine, Risperidone, and Ziprasidone in first episode never-treated psychosis
Scientific title
Antipsychotic discontinuation in first-episode never-treated psychosis: an open randomised clinical trial involving Haloperidol, Olanzapine, Quetiapine, Risperidone, and Ziprasidone
Secondary ID [1] 252998 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Antipsychotic discontinuation in first episode psychosis 258601 0
Condition category
Condition code
Mental Health 258694 258694 0 0
Schizophrenia
Mental Health 258744 258744 0 0
Psychosis and personality disorders
Mental Health 258745 258745 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients were randomized to open-label antipsychotic treatment with the following dose ranges: olanzapine 7.5-40 mg/day, risperidone 1.5-7.0 mg/day, quetiapine 100–1500 mg/day, and ziprasidone 40–240 mg/day. Study medication was administered orally with the doses prescribed at the treating psychiatrist's discretion. Participants randomized to each second generation antipsychotic received the assigned antipsychotic for 12 months on a daily basis.
Intervention code [1] 257524 0
Treatment: Drugs
Comparator / control treatment
Haloperidol arm: orally administration for 12 months on a daily basis. Doses ranged from 1.5-8.5 mg/day at the treating psychiatrist's discretion.
Control group
Active

Outcomes
Primary outcome [1] 259605 0
Retention of patients on treatment was considered a measure for effectiveness (primary outcome measure) and defined as the time to discontinuation from the antipsychotic to which patients were originally randomized.
Timepoint [1] 259605 0
Baseline (antipsychotic-naive), 6 weeks, 3 months, 9 months and 12 months.
Secondary outcome [1] 266171 0
Symptom change at each timepoint as measured by the Positive and Negative Syndrome Scale (PANSS)
Timepoint [1] 266171 0
Baseline (antipsychotic-naive), 6 weeks, 3 months, 9 months and 12 months.
Secondary outcome [2] 266246 0
Symptom change at each timepoint as measured by the Calgary Depression Symptom Scale (CDSS)
Timepoint [2] 266246 0
Baseline (antipsychotic-naive), 6 weeks, 3 months, 9 months and 12 months
Secondary outcome [3] 266247 0
Premorbid Adjustment using the PAS
Timepoint [3] 266247 0
Baseline

Eligibility
Key inclusion criteria
Showing psychotic symptoms at admission (having a score of 4 or more on PANSS positive scale items 1, 3, 5, or 6) and being naive of antipsychotic, antidepressant or mood stabilizer treatment.

Signing a consent document
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Presence of a major medical or neurological disease, mental retardation, suspicion of substance use directly contributing to the emergence of symptoms (not merely a comorbid condition) and previous treatment with psychotropic drugs.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients were recruited from psychiatric emergency units from 3 hospitals located in the metropolitan area of Barcelona, Spain.
Eligible subjects met inclusion criteria and did not meet exclusion criteria.
Allocation was performed by the psychiatrist's in charge of the patient's inclusion and consisted in contacting by phone the holder of the allocation procedure at a central administration site. Patients were immediately randomized to antipsychotic treatment to haloperidol, olanzapine, risperidone, quetiapine, or ziprasidone.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer generated randomization followed a 1:1:1:1:1 procedure into the 5 treatment groups.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 3012 0
Spain
State/province [1] 3012 0
Barcelona

Funding & Sponsors
Funding source category [1] 257978 0
Charities/Societies/Foundations
Name [1] 257978 0
Fundacio La Marato TV3
Address [1] 257978 0
Ganduxer 117, 08022 Barcelona
Country [1] 257978 0
Spain
Primary sponsor type
Commercial sector/Industry
Name
Lilly
Address
Avda de la Industria 30, 28108 Alcobendas, Madrid
Country
Spain
Secondary sponsor category [1] 257173 0
None
Name [1] 257173 0
Address [1] 257173 0
Country [1] 257173 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259980 0
Comite de Etica de Investigacion Clinica. Hospital San Rafael
Ethics committee address [1] 259980 0
Passeig Vall Hebron 107-117, 08028 Barcelona
Ethics committee country [1] 259980 0
Spain
Date submitted for ethics approval [1] 259980 0
Approval date [1] 259980 0
01/11/2001
Ethics approval number [1] 259980 0

Summary
Brief summary
The goal of this study was to perform a pragmatic, open, randomized clinical trial comparing the 12-month effectiveness (measured by time to discontinuation) of several second-generation antipsychotic drugs, with that of low doses of haloperidol in never-treated FEP.
Method: 150 patients were randomized to open-label antipsychotic treatment with haloperidol, olanzapine, risperidone, quetiapine, and ziprasidone. Retention of patients on treatment was considered a measure for effectiveness (primary outcome measure). Secondary outcomes included symptom change by antipsychotic as measured by the Positive and Negative Syndrome Scale (PANSS).
Trial website
none
Trial related presentations / publications
Ramirez N, Arranz B, Salavert J, Alvarez E, Corripio I, Duenas RM, Perez V, San L
Predictors of schizophrenia in patients with a first episode psychosis
Psychiatry Res 175: 11-14 (2010)


Arranz B, San L, Ramirez N, Duenas RM, Perez V, Salavert J, Corripio I, Alvarez E
Clinical and serotonergic predictors of nonaffective acute remitting psychosis in patients with a first-episode psychosis
Acta Psychiatr Scand 119 : 71-77 (2009)


Arranz B, Rosel P, San L, Ramirez N, Duenas RM, Salavert J, Centeno M, del Moral E.
Low baseline 5-HT2A receptors predict clinical response to olanzapine in first-episode schizophrenia patients
Psychiatry Res 153 : 103-109 (2007)


Arranz B, San L, Duenas RM, Centeno M, Ramirez N, Salavert J, del Moral E
Lower weight gain with the orally disintegrating olanzapine than with standard tablets in first-episode never treated psychotic patients
Hum Psychopharmacol Clin Exp 22 :11-15 (2007)


Reynolds GP, Arranz B, Templeman L, Fertuzinhos S, San L
Negative and depressive symptom response to antipsychotic treatment of drug-naive psychotic patients is predicted by a 5-HT1A receptor gene polymorphism
Am J Psychiatry 163: 1826-1829 (2006)


Templeman LA, Reynolds GP, Arranz B, San L
Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis
Pharmacogenet Genomics 15(4): 195-200 (2005)


Arranz B, Rosel P, Ramirez N, Duenas MR, Fernandez P, Sanchez JM, Navarro M.A., San L
Insulin resistance and increased leptin concentrations in antipsychotic-free and not in naive first-episode schizophrenic patients
J Clin Psychiatry 65 :1335-1342 (2004)
Public notes

Contacts
Principal investigator
Name 31858 0
Address 31858 0
Country 31858 0
Phone 31858 0
Fax 31858 0
Email 31858 0
Contact person for public queries
Name 15105 0
Luis San, MD, PhD
Address 15105 0
Passeig Sant Joan de Deu, 2
ES 08950 Esplugues de Llobregat, Barcelona
Country 15105 0
Spain
Phone 15105 0
+34 629736820
Fax 15105 0
Email 15105 0
12636LSM@COMB.CAT
Contact person for scientific queries
Name 6033 0
Luis San, MD, PhD
Address 6033 0
Passeig Sant Joan de Deu, 2
ES 08950 Esplugues de Llobregat, Barcelona
Country 6033 0
Spain
Phone 6033 0
+34 629736820
Fax 6033 0
Email 6033 0
12636LSM@COMB.CAT

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary