Clinical trial NCT00132314: Long-Acting Injectable Risperidone in the Treatment of Schizophrenia
Official title: CSP #555 - Long-Acting Injectable Risperidone in the Treatment of Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizoaffective Disorder
Schizophrenia
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2005-08-19
Enrollment: 382
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hospitalization-free Survival - Time to Event
timeFrame: From randomization until date of first re-hospitalization, assessed up to 24 months
measure: Hazard Ratio for Hospitalization
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Tuscaloosa
country: United States
facility: VA Medical Center, Tuscaloosa
state: Alabama
city: Long Beach
country: United States
facility: VA Medical Center, Long Beach
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
city: West Haven
country: United States
facility: VA Connecticut Health Care System (West Haven)
state: Connecticut
city: Miami
country: United States
facility: VA Medical Center, Miami
state: Florida
city: Augusta
country: United States
facility: VA Medical Center, Augusta
state: Georgia
city: Chicago
country: United States
facility: Jesse Brown VAMC (WestSide Division)
state: Illinois
city: Boston
country: United States
facility: VA Medical Center, Jamaica Plain Campus
state: Massachusetts
city: Detroit
country: United States
facility: John D. Dingell VA Medical Center, Detroit
state: Michigan
city: Minneapolis
country: United States
facility: VA Medical Center, Minneapolis
state: Minnesota
city: Kansas City
country: United States
facility: VA Medical Center, Kansas City MO
state: Missouri
city: Omaha
country: United States
facility: VA Medical Center, Omaha
state: Nebraska
city: Albuquerque
country: United States
facility: New Mexico VA Health Care System, Albuquerque
state: New Mexico
city: New York
country: United States
facility: New York Harbor HCS
state: New York
city: Cleveland
country: United States
facility: VA Medical Center, Cleveland
state: Ohio
city: Philadelphia
country: United States
facility: VA Medical Center, Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center (152)
state: Texas
city: Waco
country: United States
facility: Central Texas Veterans Health Care System - Waco
state: Texas
city: Seattle
country: United States
facility: VA Puget Sound Health Care System, Seattle
state: Washington
Study officials:
affiliation: VA Connecticut Health Care System (West Haven)
name: Robert A. Rosenheck, AB MD
role: STUDY_CHAIR
References:
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 Apr;8(2):196-204. doi: 10.1177/1740774510392931. Epub 2011 Jan 26.
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/NEJMoa1005987.
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.
citation: 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.
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. 2013 Oct 30;209(3):291-6. doi: 10.1016/j.psychres.2013.01.016. Epub 2013 Mar 7.
citation: Hoblyn JC, Rosenheck RA, Leatherman S, Weil L, Lew R; CSP 555 Investigator Group. Veteran subjects willingness to participate in schizophrenia clinical trials. Psychiatr Q. 2013 Jun;84(2):209-18. doi: 10.1007/s11126-012-9240-4.