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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
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Northwell Health

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Schizophrenia
Schizoaffective Disorder
Interventions Drug: Risperidone microspheres
Drug: Risperidone
Drug: Olanzapine
Drug: Quetiapine
Drug: Ziprasidone
Drug: Aripiprazole
Drug: Paliperidone
Enrollment 357
Recruitment Details  
Pre-assignment Details 357 individuals consented to participation. However, 52 were either ineligible, withdrew consent, or lost to followup. Therefore, 305 individuals were randomized.
Arm/Group Title Injectable Oral
Hide Arm/Group Description

Participants assigned to receive long-acting injectable risperidone

Risperidone microspheres: Minimum dose is 12.5 mg every 2 weeks. Maximum dose is 75 mg every 2 weeks.

Participants assigned to receive oral "atypical" antipsychotic medication

Risperidone: Target dose is 4 mg/day.

Olanzapine: Target dose is 15 mg/day.

Quetiapine: Target dose is 600 mg/day.

Ziprasidone: Target dose is 120 mg/day.

Aripiprazole: Target dose is 20 mg/day.

Paliperidone: Target dose is 6 mg/day.

Period Title: Overall Study
Started 153 152
Completed 72 72
Not Completed 81 80
Arm/Group Title Injectable Oral Total
Hide Arm/Group Description

Participants assigned to receive long-acting injectable risperidone

Risperidone microspheres: Minimum dose is 12.5 mg every 2 weeks. Maximum dose is 75 mg every 2 weeks.

Participants assigned to receive oral "atypical" antipsychotic medication

Risperidone: Target dose is 4 mg/day.

Olanzapine: Target dose is 15 mg/day.

Quetiapine: Target dose is 600 mg/day.

Ziprasidone: Target dose is 120 mg/day.

Aripiprazole: Target dose is 20 mg/day.

Paliperidone: Target dose is 6 mg/day.

Total of all reporting groups
Overall Number of Baseline Participants 153 152 305
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 153 participants 152 participants 305 participants
38.18  (11.8) 38.23  (12.3) 38.2  (12.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 153 participants 152 participants 305 participants
Female
45
  29.4%
42
  27.6%
87
  28.5%
Male
108
  70.6%
110
  72.4%
218
  71.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 153 participants 152 participants 305 participants
Caucasian 81 78 159
African American 45 40 85
Hispanic 27 31 58
Other 0 3 3
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 153 participants 152 participants 305 participants
153 152 305
Clinical Global Impressions (CGI) Severity Scale   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 153 participants 152 participants 305 participants
4.1  (0.84) 4.0  (0.77) 4.04  (0.80)
[1]
Measure Description:

The Clinical Global Impressions Severity Scale is one item completed by a clinician rater. "Considering your total clinical experience with this patient population, how mentally ill is the patient at this time?" The seven possible ratings are as follows.

  1. = Normal, not at all.
  2. = Borderline mentally ill.
  3. = Mildly ill.
  4. = Moderately ill.
  5. = Markedly ill.
  6. = Severely ill
  7. = Among the most extremely ill patients.
1.Primary Outcome
Title Substantial Clinical Deterioration Measured by Psychotic Symptoms
Hide Description 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.
Time Frame Measured throughout study up to 30 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
We conducted a mixed model regression analysis with two treatment groups X time psychosis cluster scores at each 3 monthly observation from baseline to 30 months. Missing data were treated as MAR
Arm/Group Title Injectable Oral
Hide Arm/Group Description:

Participants assigned to receive long-acting injectable risperidone

Risperidone microspheres: Minimum dose is 12.5 mg every 2 weeks. Maximum dose is 75 mg every 2 weeks.

Participants assigned to receive oral "atypical" antipsychotic medication

Risperidone: Target dose is 4 mg/day.

Olanzapine: Target dose is 15 mg/day.

Quetiapine: Target dose is 600 mg/day.

Ziprasidone: Target dose is 120 mg/day.

Aripiprazole: Target dose is 20 mg/day.

Paliperidone: Target dose is 6 mg/day.

Overall Number of Participants Analyzed 153 152
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
1.8
(1.7 to 1.9)
2.0
(1.9 to 2.2)
2.Secondary Outcome
Title Number of Patients Discontinuing From the Study
Hide Description [Not Specified]
Time Frame Measured throughout study up to 30 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Injectable Oral
Hide Arm/Group Description:

Participants assigned to receive long-acting injectable risperidone

Risperidone microspheres: Minimum dose is 12.5 mg every 2 weeks. Maximum dose is 75 mg every 2 weeks.

Participants assigned to receive oral "atypical" antipsychotic medication

Risperidone: Target dose is 4 mg/day.

Olanzapine: Target dose is 15 mg/day.

Quetiapine: Target dose is 600 mg/day.

Ziprasidone: Target dose is 120 mg/day.

Aripiprazole: Target dose is 20 mg/day.

Paliperidone: Target dose is 6 mg/day.

Overall Number of Participants Analyzed 153 152
Measure Type: Number
Unit of Measure: participants
81 80
3.Secondary Outcome
Title Number of Days in Hospital
Hide Description [Not Specified]
Time Frame Measured throughout study up to 30 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
These data were not collected.
Arm/Group Title Injectable Oral
Hide Arm/Group Description:

Participants assigned to receive long-acting injectable risperidone

Risperidone microspheres: Minimum dose is 12.5 mg every 2 weeks. Maximum dose is 75 mg every 2 weeks.

Participants assigned to receive oral "atypical" antipsychotic medication

Risperidone: Target dose is 4 mg/day.

Olanzapine: Target dose is 15 mg/day.

Quetiapine: Target dose is 600 mg/day.

Ziprasidone: Target dose is 120 mg/day.

Aripiprazole: Target dose is 20 mg/day.

Paliperidone: Target dose is 6 mg/day.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Control of Psychiatric Symptoms
Hide Description Brief Psychiatric Rating Scale (BPRS) total score
Time Frame Measured throughout study up to 30 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
These data were not collected. No data displayed because Outcome Measure has zero total participants analyzed.
Arm/Group Title Injectable Oral
Hide Arm/Group Description:

Participants assigned to receive long-acting injectable risperidone

Risperidone microspheres: Minimum dose is 12.5 mg every 2 weeks. Maximum dose is 75 mg every 2 weeks.

Participants assigned to receive oral "atypical" antipsychotic medication

Risperidone: Target dose is 4 mg/day.

Olanzapine: Target dose is 15 mg/day.

Quetiapine: Target dose is 600 mg/day.

Ziprasidone: Target dose is 120 mg/day.

Aripiprazole: Target dose is 20 mg/day.

Paliperidone: Target dose is 6 mg/day.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Quality of Life Measures
Hide Description Scale of Functioning (SOF)
Time Frame Measured throughout study up to 30 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
No data displayed because Outcome Measure has zero total participants analyzed. Data not collected.
Arm/Group Title Injectable Oral
Hide Arm/Group Description:

Participants assigned to receive long-acting injectable risperidone

Risperidone microspheres: Minimum dose is 12.5 mg every 2 weeks. Maximum dose is 75 mg every 2 weeks.

Participants assigned to receive oral "atypical" antipsychotic medication

Risperidone: Target dose is 4 mg/day.

Olanzapine: Target dose is 15 mg/day.

Quetiapine: Target dose is 600 mg/day.

Ziprasidone: Target dose is 120 mg/day.

Aripiprazole: Target dose is 20 mg/day.

Paliperidone: Target dose is 6 mg/day.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Side Effects and Metabolic Measures
Hide Description 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.
Time Frame Measured throughout study up to 30 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Injectable Oral
Hide Arm/Group Description:

Participants assigned to receive long-acting injectable risperidone

Risperidone microspheres: Minimum dose is 12.5 mg every 2 weeks. Maximum dose is 75 mg every 2 weeks.

Participants assigned to receive oral "atypical" antipsychotic medication

Risperidone: Target dose is 4 mg/day.

Olanzapine: Target dose is 15 mg/day.

Quetiapine: Target dose is 600 mg/day.

Ziprasidone: Target dose is 120 mg/day.

Aripiprazole: Target dose is 20 mg/day.

Paliperidone: Target dose is 6 mg/day.

Overall Number of Participants Analyzed 143 148
Mean (Standard Deviation)
Unit of Measure: units on a scale
Bruising easily 1.43  (0.71) 1.48  (0.75)
Rash 1.53  (0.78) 1.44  (0.71)
Urticaria (hives, itching) 1.60  (0.69) 1.71  (0.84)
Blurred vision 1.76  (0.73) 1.91  (0.83)
sedation/drowsiness 2.34  (0.87) 2.53  (0.78)
Restlessness 2.48  (0.76) 2.43  (0.82)
Insomnia 2.38  (0.89) 2.36  (0.94)
Malaise (weakness, fatigue) 2.22  (0.85) 2.14  (0.87)
Stiffness 2.01  (0.82) 1.97  (0.85)
Tremor 1.77  (0.72) 1.75  (0.80)
Dizziness 1.82  (0.79) 1.78  (0.82)
Headache 1.99  (0.88) 1.89  (0.90)
Fever 1.27  (0.49) 1.24  (0.46)
Sore Throat 1.64  (0.78) 1.57  (0.69)
Dry Mouth 2.36  (0.92) 2.25  (0.94)
Hypersalivation 1.76  (0.80) 1.84  (0.94)
Enuresis 1.63  (0.89) 1.56  (0.83)
Constipation 1.75  (0.86) 1.64  (0.82)
Diarrhea 1.65  (0.86) 1.68  (0.81)
Anorexia (loss of appetite) 1.89  (0.86) 1.69  (0.84)
Nausea 1.78  (0.82) 1.72  (0.80)
Vomiting 1.48  (0.72) 1.51  (0.76)
Menstrual Irregularity 1.62  (0.96) 1.55  (0.86)
Breast tenderness/galactorrhea 1.39  (0.69) 1.32  (0.61)
Time Frame [Not Specified]
Adverse Event Reporting Description 305 participants were randomized. However, 9 never received study medication. Therefore, SAE results are reported for 296 participants. 5 subjects did not have postbaseline AE ratings, and therefore AE results are reported for 291 participants.
 
Arm/Group Title Injectable Oral
Hide Arm/Group Description

Participants assigned to receive long-acting injectable risperidone

Risperidone microspheres: Minimum dose is 12.5 mg every 2 weeks. Maximum dose is 75 mg every 2 weeks.

Participants assigned to receive oral "atypical" antipsychotic medication

Risperidone: Target dose is 4 mg/day.

Olanzapine: Target dose is 15 mg/day.

Quetiapine: Target dose is 600 mg/day.

Ziprasidone: Target dose is 120 mg/day.

Aripiprazole: Target dose is 20 mg/day.

Paliperidone: Target dose is 6 mg/day.

All-Cause Mortality
Injectable Oral
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Injectable Oral
Affected / at Risk (%) Affected / at Risk (%)
Total   61/146 (41.78%)   48/150 (32.00%) 
Psychiatric disorders     
first relapse often hospitalization *  61/146 (41.78%)  48/150 (32.00%) 
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Injectable Oral
Affected / at Risk (%) Affected / at Risk (%)
Total   143/143 (100.00%)   148/148 (100.00%) 
Psychiatric disorders     
anorexia  [1]  143/143 (100.00%)  148/148 (100.00%) 
Indicates events were collected by systematic assessment
[1]
Anorexia was higher in injectable arm than in oral arm.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Peter F. Buckley, MD
Organization: Medical College of Georgia, Georgia Regents University
Phone: 706-721-2231
Responsible Party: Northwell Health
ClinicalTrials.gov Identifier: NCT00330863     History of Changes
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 Submitted: May 26, 2006
First Posted: May 29, 2006
Results First Submitted: September 4, 2015
Results First Posted: July 10, 2018
Last Update Posted: July 10, 2018