Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Clozapine, treatment as usual.
- Who it may be relevant to
- Registry conditions: Schizophrenia, Schizoaffective Disorder. Basic parameters: 18 years — 65 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
Two-hundred and eighty individuals with schizophrenia who have a recent history of violent acts will be randomized in this 2-arm, parallel-group, 24-week, open-label, 7-site clinical trial to examine the effects of treatment with clozapine vs antipsychotic treatment as usual (TAU) for reducing the risk of violent acts in real-world settings
Detailed description
This is a single-blind, open-label, randomized, active comparator (TAU) controlled clinical trial to examine the effects of clozapine vs. TAU on the risk for violent acts as measured by the MacArthur Community Violence Interview (MCVI) and to examine the effects of clozapine vs. TAU on the Excitement Factor of the PANSS. Adults age 18-65 with schizophrenia or schizoaffective disorder who have committed a violent act within 6 months and are appropriate for treatment with clozapine or TAU will receive treatment for 24 weeks which will be naturalistically administered. Participants will also participate in assessments and appropriate medical monitoring which will include blood draws, pharmacokinetic blood samples, and physical exams, etc. Cox proportional hazards survival modeling will be used to test the association between treatment group and time until first violent act after randomization (i.e., number of weeks form randomization to violent act).
Interventions
- Drug Clozapine
treatment will occur naturalistically, as per standard clinical guidelines - Drug treatment as usual
naturalistic treatment with any other antipsychotic medication except clozapine
Primary outcome measures
- Effectiveness outcome: Violent acts [Time frame: Time to violent act from randomization to treatment completion (24 weeks)]
- Target engagement outcome: Excitement Factor of the Positive and Negative Syndrome Scale (PANSS) [Time frame: Randomization to end of study treatment (24 weeks)]
Secondary outcome measures (2)
- Effect on aggression [Time frame: Randomization to end of treatment (24 weeks)]
- Positive symptoms and substance use [Time frame: Randomization to end of treatment (24 weeks)]
Eligibility criteria
Inclusion criteria
- Diagnostic and Statistical Manual-5 (DSM-5) diagnosis of schizophrenia or schizoaffective disorder by the Structured Clinical Interview for DSM-5 (SCID-5)
- commission of a minor or serious act of violence as measured by the MCVI in the last six months
- willing and able to provide informed consent
- medically stable in judgment of physician providing study treatment
- appropriate for treatment with either clozapine or TAU, i.e., that there is clinical equipoise between the two treatment options. Individuals who are currently medication free or on any antipsychotic, with the exception of clozapine or long-acting injectable medication with a dosing interval of more than 30 days will be eligible
Exclusion criteria
- An unstable of serious medical or neurological condition including a myeloproliferative disorder or condition that surprises the bone marrow
- A history of intolerance/allergy to clozapine (e.g., agranulocytosis, small bowel obstruction, or myocarditis)
- A history of intellectual impairment
- pregnant or lactating women; women who are able to become pregnant but who are not willing to sue effective methods of birth control
- Individuals who score a 3, 4, or 5 within the previous month on the suicidal ideation section of the Columbia Suicide Severity Rating Scale (CSSRS), have any suicidal behavior (not including Not Suicidal Self Injury) within the previous 3 months, or are, in the opinion of the investigator, at too high of a risk for suicide to be safety treated in a randomized trial in which they may not be treated with clozapine
- Documented intolerance to or lack of any therapeutic benefit with clozapine after a full trial
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Single blind
- Primary purpose
- Treatment
Study locations
United States · 7 centers
- University of California, Los Angeles — Los Angeles
- Augusta University Research Institute, Inc. — Augusta
- University of Maryland School of Medicine — Baltimore
- NYU Langone Medical Center — New York
- New York State Psychiatric Institute — New York
- Manhattan Psychiatric Center — New York
- University of North Carolina at Chapel Hill — Chapel Hill
Identifiers
NCT: NCT05208190 · I20-02054 · 1R01MH120317-01A1