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Comparative Study of Aripiprazole, Quetiapine and Ziprasidone in the Treatment of First Episode Nonaffective Psychosis (PAFIP2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02305823
Recruitment Status : Completed
First Posted : December 3, 2014
Last Update Posted : March 14, 2017
Sponsor:
Collaborators:
Centro de Investigación Biomédica en Red de Salud Mental
Instituto de Investigación Marqués de Valdecilla
Information provided by (Responsible Party):
Benedicto Crespo-Facorro, Fundación Marques de Valdecilla

Brief Summary:
The selection of antipsychotic in early stages of the illness is mainly determined by its clinical effectiveness. Second generation antipsychotics (SGAs) are the first line drug treatment for individuals suffering from schizophrenia. It is clear that SGAs are not a homogeneous group and clinical effects and profile of side effects differ between SGAs. Differences among antipsychotics in terms of effectiveness have turned out to be a topic of increasing research interest, although comparisons between the different SGAs are scarce. In first episode of psychosis, SGAs have shown a higher treatment effectiveness compared to first generation antipsychotics (FGAs) (findings primarily driven by Haloperidol). Less evident seems to be the notion that some of the SGAs might be more effective (in terms of treatment discontinuation) than others. Most of the medium-term randomized studies have shown similar rates of all-cause treatment discontinuation in first episode patients treated with different SGAs. It may be concluded that more randomized controlled trails should be accomplished to determine the position of frequently used SGAs in clinical practice. The investigators undertook this study with the major objective of comparing the clinical effectiveness of three widely utilized SGAs (Aripiprazole, Ziprasidone and Quetiapine) in the acute treatment of first-episode non-affective psychosis individuals.

Condition or disease Intervention/treatment Phase
Schizophrenia Psychotic Disorders Drug: Aripiprazole Drug: Quetiapine Drug: Ziprasidone Phase 4

Detailed Description:

Study setting and financial support: data for the present investigation were obtained from an ongoing epidemiological and three-year longitudinal intervention program of first-episode psychosis (PAFIP) conducted at the outpatient clinic and the inpatient unit at the University Hospital Marqués de Valdecilla, Spain. Conforming to international standards for research ethics, this program was approved by the local institutional review board. Patients meeting inclusion criteria and their families provided written informed consent to be included in the PAFIP. The Mental Health Services of Cantabria provided funding for implementing the program. None pharmaceutical company supplied any financial support to it.

Study design: this is a prospective, randomized, flexible-dose, open-label study. At study intake, all patients but eight were antipsychotic naïve. Dose ranges were 5-20 mg /day Aripiprazole, 40-160 mg/day Ziprasidone and 100-600 mg/day Quetiapine. Rapid titration schedule (5-day), until optimal dose was reached, was as a rule used unless severe side effects occur. At the treating physician´s discretion, the dose and type of antipsychotic medication could be changed based on clinical efficacy and the profile of side effects during the follow-up period. Antimuscarinic medication, Lormetazepam and Clonazepam were permitted for clinical reasons. No antimuscarinic agents were administered prophylactically. Antidepressants (Sertraline) and mood stabilizers (lithium) were permitted if clinically needed.

The severity scale of the Clinical Global Impression (CGI) scale, the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive symptoms (SAPS), the Scale for the Assessment of Negative symptoms (SANS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Young Mania Rating Scale (YMRS) were used to evaluate symptomatology. To assess general adverse event experiences the Scale of the Udvalg for Kliniske Undersogelser (UKU), the Simpson-Angus Rating Scale (SARS) and the Barnes Akathisia Scale (BAS) were used. The same trained psychiatrist (BC-F) completed all clinical assessments.

The adverse events were evaluated using the UKU Side effect rating scale. Those treatment-emergent adverse events that occurred at a rate of at least 10% in either treatment group are considered. Treatment-emergent akathisia (BAS) and extrapyramidal symptoms (SARS) were assessed by both baseline-to-end changes and newly emergent categorical changes.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 203 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase IV Study of the Effectiveness of Aripiprazole, Quetiapine, and Ziprasidone in the Treatment of First Episode of Non-affective Psychosis Individuals Included in the First Episode Psychosis Clinical Program II (PAFIP II)
Actual Study Start Date : October 2005
Actual Primary Completion Date : February 2011
Actual Study Completion Date : May 2014


Arm Intervention/treatment
Active Comparator: Aripiprazole
Oral, dose range 5-30 mg/day, once or twice a day, during study duration
Drug: Aripiprazole
Other Name: Abilify

Active Comparator: Quetiapine
Oral, dose range 100-600 mg/day, once or twice a day, during study duration
Drug: Quetiapine
Other Name: Seroquel

Active Comparator: Ziprasidone
Oral, dose range 40-160 mg/day, once or twice a day, during study duration
Drug: Ziprasidone
Other Name: Zeldox




Primary Outcome Measures :
  1. Effectiveness of antipsychotics (percentage of discontinuation of the initially assigned treatment) [ Time Frame: 6 weeks ]
    The main outcomes of effectiveness were the percentage of discontinuation of the initially assigned treatment (patients who completed the 6 weeks follow-up assessment and changed initial antipsychotic) and the mean time to all-cause medication discontinuation. Four reasons for the discontinuation were recorded: 1.- insufficient efficacy; 2.- marked side-effects; 3.- patient reported non-adherence and 4.- other causes. If more than one reason for discontinuation was present, the most important reason according to the above ranking was selected. Data on antipsychotic treatment (doses, discontinuation and concomitant medications) were registered weekly during the first 4 weeks and at 6 week. Insufficient efficacy was established at the treating physician´s judgment only after at least three weeks of treatment.


Secondary Outcome Measures :
  1. Change in general psychopathology measured by the Brief Psychiatric Rating Scale (BPRS) [ Time Frame: 6 weeks, 3 months and 1 year ]
    Measured by BPRS. The patients were defined as responders to the optimum dose of antipsychotic at 6 weeks if a >40% reduction of the BPRS scores at intake and had a CGI severity score of ≤ 4. In addition, we also explored to rate of responders if a cutoff of ≥ 50% reduction of the BPRS total scores at intake was used.

  2. Change in positive and negative symptoms measured by the Scale for the Assessment of Negative and Positive Symptoms (SANS and SAPS) [ Time Frame: 6 weeks, 3 months and 1 year ]
    Measured by SANS and SAPS.

  3. Change in the severity of depressive symptoms measured by the Calgary Depression Scale (CDS) [ Time Frame: 6 weeks, 3 months and 1 year ]
    Measured by CDS.

  4. Change in maniac symptoms measured by the Young Mania Rating Scale (YMRS) [ Time Frame: 6 weeks, 3 months and 1 year ]
    Measured by YMRS.

  5. Adherence to treatment [ Time Frame: 1 year ]

Other Outcome Measures:
  1. Relapse rate [ Time Frame: 1 year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 15-60 years.
  • Living in the catchment area.
  • Experiencing their first episode of psychosis.
  • No prior treatment with antipsychotic medication or, if previously treated, a total life time of adequate antipsychotic treatment of less than 6 weeks.
  • Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for brief psychotic disorder, schizophreniform disorder, schizophrenia, or schizoaffective disorder.

Exclusion Criteria:

  • Meeting DSM-IV criteria for drug dependence
  • Meeting DSM-IV criteria for mental retardation
  • Having a history of neurological disease or head injury.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02305823


Locations
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Spain
University Hospital Marques de Valdecilla
Santander, Cantabria, Spain, 39008
Sponsors and Collaborators
Fundación Marques de Valdecilla
Centro de Investigación Biomédica en Red de Salud Mental
Instituto de Investigación Marqués de Valdecilla
Investigators
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Principal Investigator: Benedicto Crespo-Facorro, Professor University Hospital Marqués de Valdecilla, IDIVAL, Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain. CIBERSAM Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Benedicto Crespo-Facorro, Associate Professor of Psychiatry, Fundación Marques de Valdecilla
ClinicalTrials.gov Identifier: NCT02305823    
Other Study ID Numbers: AZQ2005
CI 2005-0308007 ( Other Grant/Funding Number: SENY Fundació Research Grant CI 2005-0308007 )
First Posted: December 3, 2014    Key Record Dates
Last Update Posted: March 14, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Benedicto Crespo-Facorro, Fundación Marques de Valdecilla:
psychosis
antipsychotic agents
treatment
effectiveness
Additional relevant MeSH terms:
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Schizophrenia
Psychotic Disorders
Mental Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Aripiprazole
Quetiapine Fumarate
Ziprasidone
Antidepressive Agents
Psychotropic Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin 5-HT1 Receptor Agonists
Serotonin Receptor Agonists
Serotonin Agents
Serotonin 5-HT2 Receptor Antagonists
Serotonin Antagonists
Dopamine D2 Receptor Antagonists
Dopamine Antagonists