Long-Acting Injectable Risperidone in the Treatment of Schizophrenia

Schizophrenia Clinical Trial

Official title:

CSP #555 - Long-Acting Injectable Risperidone in the Treatment of Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00132314
• Other study ID #: 555
• Status: Completed
• Phase: Phase 3
• First received: August 17, 2005
• Last updated: October 30, 2013
• Start date: September 2006
• Est. completion date: September 2009

Study information

• Verified date: October 2013
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

In the proposed study 450 veterans with a primary diagnosis of schizophrenia who had at least one psychiatric hospitalization for schizophrenia in the previous 2 years would be randomly assigned at 16 VA medical centers to long-acting injectable risperidone or doctor's choice of oral antipsychotic medication (i.e., excluding other long-acting injectable medications, but not specifying any particular oral agents or dosages). Recruitment would take 27 months to complete, and the study would continue for a third year to allow 9 months of follow-up for the last patient recruited. All patients would be treated from the time of entry up to the end of the three-year study period. Follow-up assessments would continue quarterly. Treatments would not be blinded since giving placebo injections to the comparison group would interfere with the goal of comparing the acceptability of two different methods of medication administration. However, end points will be blindly rated.

Description:

The purpose of the study is to assess the effectiveness of long-acting injectable risperidone on psychiatric inpatient hospitalization, schizophrenia symptoms, quality of life, medication adherence, side effects, and health care costs.

Objectives:

Primary: To evaluate the impact of long-acting intramuscular (IM) risperidone on risk of inpatient psychiatric hospitalization in comparison to standard oral antipsychotic treatment in a randomized controlled trial to be conducted with 450 veterans diagnosed with schizophrenia or schizoaffective disorder at 16 VA medical centers over three years.

Secondary: To evaluate adherence, health benefits, and costs of long-acting IM risperidone as compared to standard oral antipsychotic treatment as measured by: a) symptom reduction over 12 months, b) time to all-cause medication discontinuation, c) quality of life, d) VA and non-VA health service use and related costs, e) medication side effects, f) violent behavior, g) use of concomitant medication, and h) the incremental cost-effectiveness ratio.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 382
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age 18 years or older.

2. Diagnosed with schizophrenia or schizoaffective disorder by the Structured Clinical Interview for Diagnosis (SCID) (Spitzer and First et al., 1996).

3. Patients should

1. have been hospitalized in the two years before study entry on a psychiatric inpatient unit, or

2. document explicit current evidence of increased use of outpatient services such as additional visits, day treatment or non-hospital residential treatment, increased dosage of medications or addition of concomitant psychotropic medications.

The b criterion will promptly be adjudicated by the study chairmen on a case-by case basis to insure credibility.

4. .Adequate transportation is available and the participant lives within a travel time of less than 1.5 hours, allowing attendance at all scheduled visits.

5. Use of an acceptable method of birth control by female patients who have a possibility of becoming pregnant (safety concerns).

6. Able to demonstrate decisional capacity in order to give informed consent as assessed by the MacArthur Competence Assessment Tool (MacCAT) (Appelbaum and Grisso, 1996). Guardian consent is acceptable where applicable.

7. Dually diagnosed patients with both schizophrenia and addictive disorders would be included in this study but should not be in need of acute detoxification for physiologic substance dependence (excluding nicotine) in the past 30 days.

Exclusion Criteria:

1. Physiologic substance dependence requiring detoxification (excluding nicotine) in the past 30 days (substance abuse is not an exclusion).

2. Intolerance of risperidone.

3. Intolerance of intramuscular injection.

4. Current treatment with depot antipsychotic medication.

5. Current treatment with oral clozapine or presence of refractory schizophrenia that, in the treating psychiatrist's opinion, requires clozapine.

6. Hepatic or renal problems AST or ALT (>2 times upper limit of normal);

7. Elevated bilirubin (>1.2), BUN (>24), creatinine (>1.7).

8. Unstable, serious medical condition or one requiring acute medical treatment, or anticipation of hospitalization for extended care.

9. Dementia, epilepsy, insulin-dependent diabetes, anticoagulation with coumadin.

10. Unstable living arrangements or not planning to remain in the area for the next year.

11. Legal entanglements or pending legal charges with potential of incarceration.

12. Assault or suicide gesture currently needing acute intervention.

13. Concurrent participation in another clinical trial with an investigational drug during the last 30 days.

14. Pregnant or lactating women or women planning to become pregnant.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia

Intervention

Drug:
• IM risperidone
long-acting injectable risperidone
• oral antipsychotic medication
doctor's choice (excluding other long-acting injectable medications but not specifying any particular oral agents or dosages)

Locations

Country	Name	City	State
United States	New Mexico VA Health Care System, Albuquerque	Albuquerque	New Mexico
United States	VA Medical Center, Augusta	Augusta	Georgia
United States	VA Medical Center, Jamaica Plain Campus	Boston	Massachusetts
United States	Jesse Brown VAMC (WestSide Division)	Chicago	Illinois
United States	VA Medical Center, Cleveland	Cleveland	Ohio
United States	John D. Dingell VA Medical Center, Detroit	Detroit	Michigan
United States	Michael E. DeBakey VA Medical Center (152)	Houston	Texas
United States	VA Medical Center, Kansas City MO	Kansas City	Missouri
United States	VA Medical Center, Long Beach	Long Beach	California
United States	VA Medical Center, Miami	Miami	Florida
United States	VA Medical Center, Minneapolis	Minneapolis	Minnesota
United States	New York Harbor HCS	New York	New York
United States	VA Medical Center, Omaha	Omaha	Nebraska
United States	VA Palo Alto Health Care System	Palo Alto	California
United States	VA Medical Center, Philadelphia	Philadelphia	Pennsylvania
United States	VA Puget Sound Health Care System, Seattle	Seattle	Washington
United States	VA Medical Center, Tuscaloosa	Tuscaloosa	Alabama
United States	Central Texas Veterans Health Care System - Waco	Waco	Texas
United States	VA Connecticut Health Care System (West Haven)	West Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

References & Publications (5)

Barnett PG, Scott JY, Krystal JH, Rosenheck RA; CSP 555 Research Group. Cost and cost-effectiveness in a randomized trial of long-acting risperidone for schizophrenia. J Clin Psychiatry. 2012 May;73(5):696-702. doi: 10.4088/JCP.11m07070. — View Citation

Barnett PG, Scott JY, Rosenheck RA; CSP 555 Study Group. How do clinical trial participants compare to other patients with schizophrenia? Schizophr Res. 2011 Aug;130(1-3):34-9. doi: 10.1016/j.schres.2011.03.033. Epub 2011 Apr 22. — View Citation

Rosenheck RA, Krystal JH, Lew R, Barnett PG, Fiore L, Valley D, Thwin SS, Vertrees JE, Liang MH; CSP555 Research Group. Long-acting risperidone and oral antipsychotics in unstable schizophrenia. N Engl J Med. 2011 Mar 3;364(9):842-51. doi: 10.1056/NEJMoa1 — View Citation

Rosenheck RA, Krystal JH, Lew R, Barnett PG, Thwin SS, Fiore L, Valley D, Huang GD, Neal C, Vertrees JE, Liang MH; CSP 555 Research Group. Challenges in the design and conduct of controlled clinical effectiveness trials in schizophrenia. Clin Trials. 2011 — View Citation

Thwin SS, Hermes E, Lew R, Barnett P, Liang M, Valley D, Rosenheck R. Assessment of the minimum clinically important difference in quality of life in schizophrenia measured by the Quality of Well-Being Scale and disease-specific measures. Psychiatry Res. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hospitalization-free Survival - Time to Event	A hospitalization-free survival was defined as the time from the date of randomization to the time of a psychiatric hospitalization (in both VA and non-VA hospitals) or, in the case of patients who were hospitalized at randomization, the time from the date of discharge from the initial stay to subsequent hospitalization. Patients without an event were censored at 24 months after the date of randomization.	From randomization until date of first re-hospitalization, assessed up to 24 months	No
Primary	Hazard Ratio for Hospitalization	Hazard ratio of LAI versus Oral for psychiatric hospitalization (in both VA and non-VA hospitals), after randomization up to 24 months, obtained from a Cox proportional hazards model.	24 months	No