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

Study Description

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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.

Study Design

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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

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Outcome Measures

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Primary Outcome Measures :

1. Time to relapse, where "relapse" is defined as psychiatric hospitalization [ Time Frame: Measured throughout study ]
2. Increase in the level of psychiatric care required to avert hospitalization [ Time Frame: Measured throughout study ]
3. Substantial clinical deterioration measured by psychotic symptoms [ Time Frame: Measured throughout study ]

Secondary Outcome Measures :

1. Number of patients discontinuing from the study [ Time Frame: Measured throughout study ]
2. Number of days in hospital [ Time Frame: Measured throughout study ]
3. Visits to hospital emergency rooms [ Time Frame: Measured throughout study ]
4. Control of psychiatric symptoms [ Time Frame: Measured throughout study ]
5. Quality of life measures [ Time Frame: Measured throughout study ]
6. Side effects and metabolic measures [ Time Frame: Measured throughout study ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

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Locations

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)

Investigators

Study Director:	Nina R. Schooler, PhD	Steering and Implementation Center

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

Buckley PF, Schooler NR, Goff DC, Hsiao J, Kopelowicz A, Lauriello J, Manschreck T, Mendelowitz AJ, Miller del D, Severe JB, Wilson DR, Ames D, Bustillo J, Mintz J, Kane JM; PROACTIVE Study. Comparison of SGA oral medications and a long-acting injectable SGA: the PROACTIVE study. Schizophr Bull. 2015 Mar;41(2):449-59. doi: 10.1093/schbul/sbu067. Epub 2014 May 27.

Responsible Party:	Northwell Health
ClinicalTrials.gov Identifier:	NCT00330863 History of Changes
Other Study ID Numbers:	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
Last Update Posted:	July 15, 2014
Last Verified:	July 2014

Keywords provided by Northwell Health:

Relapse; Prevention; Schizophrenia; Injectable Medication

Additional relevant MeSH terms:

Schizophrenia; Recurrence; Psychotic Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Risperidone; Paliperidone Palmitate; Ziprasidone; Antipsychotic Agents; Aripiprazole; Olanzapine; Quetiapine Fumarate; Serotonin Antagonists	Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Dopamine Antagonists; Dopamine Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors