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Preventing Relapse in Schizophrenia: Oral Antipsychotics Compared To Injectables: Evaluating Efficacy (PROACTIVE)

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ClinicalTrials.gov Identifier: NCT00330863
Recruitment Status : Completed
First Posted : May 29, 2006
Results First Posted : July 10, 2018
Last Update Posted : July 10, 2018
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Northwell Health

Brief Summary:
This study is designed to find out whether taking antipsychotic medication once every two weeks by injection compared to taking daily oral medication will help people with schizophrenia maintain better control of their symptoms.

Condition or disease Intervention/treatment Phase
Schizophrenia Schizoaffective Disorder Drug: Risperidone microspheres Drug: Risperidone Drug: Olanzapine Drug: Quetiapine Drug: Ziprasidone Drug: Aripiprazole Drug: Paliperidone Phase 4

Detailed Description:

As is the case with many chronic illnesses, it can be challenging for people with schizophrenia to take multiple pills every day on a long-term basis. At the same time, missing or discontinuing the anti-psychotic medications that treat schizophrenia substantially increases the risk of relapse and re-hospitalization. This study will determine how effective long-acting injectable risperidone is compared to oral antipsychotic medications to help patients who have schizophrenia. Patients who enroll in the study will be randomly assigned to receive either long-acting injectable risperidone or to receive oral "atypical" antipsychotic medication. The "atypical" antipsychotics that are included for patients in the oral group are: aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone. Patients in the "oral" group will receive whichever of the five "atypical" antipsychotic medications they and their study doctor decide is best for them. Patients in the "oral" group will be allowed to switch to others of the five medications during the study if they and their doctor think that is best.

Patients in this study will be evaluated at the beginning of the study and then again every two weeks for up to 30 months (2 1/2 years). Each two-week visit will take about 20 minutes. At the visit, patients will receive medication and will be examined for side effects of the medications, their vital signs (heart rate, blood pressure, weight, and waist measurement) will be measured, and they will be asked a few questions about attendance at visits and taking medication. The visit that occurs every three months will take about one hour, instead of 20 minutes, and will include additional questions, an examination for muscle stiffness or abnormal body movements, and an interview from a member of the research team conducted using computer technology. In addition, blood and urine samples may be collected about seven times throughout the 30 months of the study treatment. Patients who enroll in this study after the halfway point of the study, may not receive a full 30 months of treatment, but it is planned that all patients will have the opportunity to receive no less than 18 months of treatment.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 357 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Preventing Relapse: Oral Antipsychotics Compared To Injectables: Evaluating Efficacy (PROACTIVE)
Study Start Date : May 2006
Actual Primary Completion Date : January 2011
Actual Study Completion Date : January 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Experimental: Injectable
Participants assigned to receive long-acting injectable risperidone
Drug: Risperidone microspheres
Minimum dose is 12.5 mg every 2 weeks. Maximum dose is 75 mg every 2 weeks.
Other Name: Risperdal Consta

Active Comparator: Oral
Participants assigned to receive oral "atypical" antipsychotic medication
Drug: Risperidone
Target dose is 4 mg/day.
Other Name: Risperdal

Drug: Olanzapine
Target dose is 15 mg/day.
Other Name: Zyprexa

Drug: Quetiapine
Target dose is 600 mg/day.
Other Name: Seroquel

Drug: Ziprasidone
Target dose is 120 mg/day.
Other Name: Geodon

Drug: Aripiprazole
Target dose is 20 mg/day.
Other Name: Abilify

Drug: Paliperidone
Target dose is 6 mg/day.
Other Name: Invega

Primary Outcome Measures :
  1. Substantial Clinical Deterioration Measured by Psychotic Symptoms [ Time Frame: Measured throughout study up to 30 months ]
    Brief Psychiatric Rating Scale (BPRS) psychosis cluster. Score range is based on the score range for individual items rather than the factor total because is factors have different numbers of items. Score range is 1 -7 where 1 + no symptomatology and 7 = very severe symptoms.

Secondary Outcome Measures :
  1. Number of Patients Discontinuing From the Study [ Time Frame: Measured throughout study up to 30 months ]
  2. Number of Days in Hospital [ Time Frame: Measured throughout study up to 30 months ]
  3. Control of Psychiatric Symptoms [ Time Frame: Measured throughout study up to 30 months ]
    Brief Psychiatric Rating Scale (BPRS) total score

  4. Quality of Life Measures [ Time Frame: Measured throughout study up to 30 months ]
    Scale of Functioning (SOF)

  5. Side Effects and Metabolic Measures [ Time Frame: Measured throughout study up to 30 months ]
    The highest severity of each of 24 adverse event (AE) that was assessed.over the 30 month study period. The mean severity on a scale of 1 (none) to 4 very severe symptom was recorded at each biweekly visit. Results for each variable are summarized over time so that each subject has a single mean severity rating for each AE. There is no named scale. Each of the side effects measured is named in ways that are clear to medical readers e.g anorexia. The range is 1 none to 4 very severe. Therefore, a higher scale score is worse.

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • All schizophrenia and schizoaffective patients whose clinicians are considering long-term treatment with an "atypical" (second generation) antipsychotic medication
  • Worsening of illness (schizophrenia) within 12 months of study entry as defined by: hospitalization, increased level of clinical care, and/or present clinical Global Impressions Severity rating of moderate or worse

Exclusion Criteria:

  • First episode patients as defined by a patient who: has never received antipsychotic medication and has never been hospitalized for psychiatric illness; or, is receiving antipsychotic medication for the first time associated with a first diagnosis of schizophrenia.
  • Pregnant or breastfeeding
  • Patients with unstable medical conditions
  • Patients with previous history of failure to respond to an adequate trial of clozapine
  • Patients with a known allergy to risperidone or a previous history of failure to respond to an adequate trial of risperidone. However, patients with known allergies or failure to respond to any of the other medications (aripiprazole, olanzapine, quetiapine or ziprasidone) will not receive that medication if they are randomized to the oral medication arm, but are not excluded from the study

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): NCT00330863

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United States, California
University of California, Los Angeles
Los Angeles, California, United States, 91344
United States, Georgia
Medical College of Georgia, Department of Psychiatry
Augusta, Georgia, United States, 30912-3800
United States, Iowa
University of Iowa College of Medicine, Psychiatry Research
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Harvard Medical School -- Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Harvard Medical School -- Dr. John C. Corrigan Community Mental Health Center
Fall River, Massachusetts, United States, 02720
United States, Nebraska
Creighton University
Omaha, Nebraska, United States, 68131
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, New York
The Zucker Hillside Hospital
Glen Oaks, New York, United States, 11004
Sponsors and Collaborators
Northwell Health
National Institute of Mental Health (NIMH)
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Study Director: Nina R. Schooler, PhD Steering and Implementation Center
Publications of Results:
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Responsible Party: Northwell Health
ClinicalTrials.gov Identifier: NCT00330863    
Other Study ID Numbers: U01MH070007-01 ( U.S. NIH Grant/Contract )
U01MH070007-01 ( U.S. NIH Grant/Contract )
U01MH070023 ( U.S. NIH Grant/Contract )
U01MH070011 ( U.S. NIH Grant/Contract )
U01MH070009 ( U.S. NIH Grant/Contract )
U01MH070008 ( U.S. NIH Grant/Contract )
U01MH070017 ( U.S. NIH Grant/Contract )
U01MH070010 ( U.S. NIH Grant/Contract )
U01MH070016 ( U.S. NIH Grant/Contract )
U01MH070012 ( U.S. NIH Grant/Contract )
DSIR 83-ATAP ( Other Grant/Funding Number: National Institute of Mental Health )
First Posted: May 29, 2006    Key Record Dates
Results First Posted: July 10, 2018
Last Update Posted: July 10, 2018
Last Verified: June 2018
Keywords provided by Northwell Health:
Injectable Medication
Additional relevant MeSH terms:
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Psychotic Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Disease Attributes
Pathologic Processes
Quetiapine Fumarate
Paliperidone Palmitate
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors