Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial

Schizophrenia Clinical Trial

— REVISIT-C  

Official title:

Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05208190
• Other study ID #: I20-02054
• Secondary ID: 1R01MH120317-01A
• Status: Recruiting
• Phase: Phase 4
• Start date: March 17, 2022
• Est. completion date: February 28, 2027

Study information

• Verified date: April 2024
• Source: New York State Psychiatric Institute
• Contact: Ragy Girgis
• Phone: 646-774-5553
• Email: ragy.girgis[@]nyspi.columbia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 280
• Est. completion date: February 28, 2027
• Est. primary completion date: January 23, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia

Intervention

Drug:
• Clozapine
treatment will occur naturalistically, as per standard clinical guidelines
• treatment as usual
naturalistic treatment with any other antipsychotic medication except clozapine

Locations

Country	Name	City	State
United States	Augusta University Research Institute, Inc.	Augusta	Georgia
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of California, Los Angeles	Los Angeles	California
United States	Manhattan Psychiatric Center	New York	New York
United States	New York State Psychiatric Institute	New York	New York
United States	NYU Langone Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York State Psychiatric Institute	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Interventions to Prevent Violence	examine the effects of clozapine vs TAU on interventions to prevent violence based on a querying clinicians treating patients about interventions to prevent violence at weeks 4, 8, 16 and 24	Randomization to end of treatment (24 weeks)
Primary	Effectiveness outcome: Violent acts	violent acts as measured by the MacArthur Community Violence Interview	Time to violent act from randomization to treatment completion (24 weeks)
Primary	Target engagement outcome: Excitement Factor of the Positive and Negative Syndrome Scale (PANSS)	a composite of the scores of excitement, uncooperativeness, poor impulse control, and hostility)	Randomization to end of study treatment (24 weeks)
Secondary	Effect on aggression	examine the effects of clozapine vs TAU on aggression as measured by the Point Subtraction Aggression Paradigm	Randomization to end of treatment (24 weeks)
Secondary	Positive symptoms and substance use	explore effects of clozapine vs TAU on the positive symptom sub scale of the PANSS and alcohol and illicit substance use, how these effects influence the risk for violent acts, and the degree to which clozapine's effects on the Excitement Factor of the PANSS are independent of its effects on total positive symptoms and substance use.	Randomization to end of treatment (24 weeks)