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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
Last Update Posted : July 15, 2014
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Northwell Health

May 26, 2006
May 29, 2006
July 15, 2014
May 2006
January 2011   (Final data collection date for primary outcome measure)
  • Time to relapse, where "relapse" is defined as psychiatric hospitalization [ Time Frame: Measured throughout study ]
  • Increase in the level of psychiatric care required to avert hospitalization [ Time Frame: Measured throughout study ]
  • Substantial clinical deterioration measured by psychotic symptoms [ Time Frame: Measured throughout study ]
  • Time to relapse, where "relapse" is defined as: Psychiatric hospitalization
  • or An increase in the level of psychiatric care required to avert hospitalization
  • or Substantial clinical deterioration measured by psychotic symptoms.
Complete list of historical versions of study NCT00330863 on ClinicalTrials.gov Archive Site
  • Number of patients discontinuing from the study [ Time Frame: Measured throughout study ]
  • Number of days in hospital [ Time Frame: Measured throughout study ]
  • Visits to hospital emergency rooms [ Time Frame: Measured throughout study ]
  • Control of psychiatric symptoms [ Time Frame: Measured throughout study ]
  • Quality of life measures [ Time Frame: Measured throughout study ]
  • Side effects and metabolic measures [ Time Frame: Measured throughout study ]
  • Number of patients discontinuing from the study
  • Number of days in hospital
  • Visits to hospital emergency rooms
  • Control of psychiatric symptoms
  • Quality of life measures
  • Side effects and metabolic measures.
Not Provided
Not Provided
Preventing Relapse in Schizophrenia: Oral Antipsychotics Compared To Injectables: Evaluating Efficacy
Preventing Relapse: Oral Antipsychotics Compared To Injectables: Evaluating Efficacy (PROACTIVE)
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.

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.

Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Schizophrenia
  • Schizoaffective Disorder
  • Drug: Risperidone microspheres
    Minimum dose is 12.5 mg every 2 weeks. Maximum dose is 75 mg every 2 weeks.
    Other Name: Risperdal Consta
  • 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
  • Experimental: Injectable
    Participants assigned to receive long-acting injectable risperidone
    Intervention: Drug: Risperidone microspheres
  • Active Comparator: Oral
    Participants assigned to receive oral "atypical" antipsychotic medication
    • Drug: Risperidone
    • Drug: Olanzapine
    • Drug: Quetiapine
    • Drug: Ziprasidone
    • Drug: Aripiprazole
    • Drug: Paliperidone
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
January 2011
January 2011   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 65 Years   (Adult)
Contact information is only displayed when the study is recruiting subjects
United States
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 )
Not Provided
Not Provided
Northwell Health
Northwell Health
National Institute of Mental Health (NIMH)
Study Director: Nina R. Schooler, PhD Steering and Implementation Center
Northwell Health
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP