SchizophreniaPhase 4REVISIT-CNCT05208190
Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial
A Phase 4 study testing Clozapine and treatment as usual in people with Schizophrenia and Schizoaffective Disorder, run by New York State Psychiatric Institute at 7 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- Clozapine and treatment as usual
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- 7 sitesUnited States
- Study dates
- 17 Mar 2022to 31 Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
Augusta University Research Institute, Inc.
Augusta, Georgia, 30912
Joseph McEvoy, MD, 706-792-7021, jmcevoy@augusta.edu
- Recruiting
University of Maryland School of Medicine
Baltimore, Maryland, 21201
Deanna Kelly, PharmD, 410-402-6861, dlkelly@som.umaryland.edu
- Recruiting
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Fred Jarskog, MD, 919-842-7683, jarskog@med.unc.edu
- Recruiting
University of California, Los Angeles
Los Angeles, California, 90024
Alex Kopelowicz, MD, 818-837-8150, akopel@ucla.edu
- Recruiting
NYU Langone Medical Center
New York, New York, 10016
Donald Goff, 646-754-4843, donald.goff@nyulangone.org
- Recruiting
New York State Psychiatric Institute
New York, New York, 10032
Ragy R Girgis, MD, 646-774-5553, rg2290@columbia.edu
Ragy R Girgis, MD
- Recruiting
Manhattan Psychiatric Center
New York, New York, 10035
Jean-Pierre Lindenmayer, MD, 212-249-2720, jean-pierre.lindenmayer@nki.rfmh.org
About this study
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
Read the 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).
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Being tested
- Clozapine, treatment as usual
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClozapineDrug
Also called clozaril
treatment will occur naturalistically, as per standard clinical guidelines
naturalistic treatment with any other antipsychotic medication except clozapine
| Study group | Role | What they receive |
|---|---|---|
| Clozapine | Experimental | treatment with clozapine naturalistically administered (as per clinical guideline). Receives: Drug: Clozapine |
| Treatment as usual | Active comparator | open label naturalistic treatment as usual with any antipsychotic other than clozapine Receives: Drug: treatment as usual |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effectiveness outcome: Violent acts
violent acts as measured by the MacArthur Community Violence Interview
Measured: Time to violent act from randomization to treatment completion (24 weeks)
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)
Measured: Randomization to end of study treatment (24 weeks)
Secondary outcomes (2)
Effect on aggression
examine the effects of clozapine vs TAU on aggression as measured by the Point Subtraction Aggression Paradigm
Measured: Randomization to end of treatment (24 weeks)
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.
Measured: Randomization to end of treatment (24 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2022
- Study start17 Mar 2022
- Primary completion30 Jun 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- single-blind, open-label, randomized, active comparator (TAU) controlled clinical trial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Ragy Girgis, New York State Psychiatric Institute
- Investigators
- Ragy Girgis, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05208190
- Sponsor's protocol ID
- I20-02054
- Other IDs
- 1R01MH120317-01A1
- Acronym
- REVISIT-C
- Status last verified
- Apr 2026
- First submitted
- 12 Jan 2022
- Last updated
- 4 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT05208190
- Acronym / sponsor ID
- REVISIT-C / I20-02054
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 280 participants (estimated)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 17 Mar 2022 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 26 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- single-blind, open-label, randomized, active comparator (TAU) controlled clinical trial
| Arm | Type | Receives |
|---|---|---|
| Clozapine | Experimental | Drug: Clozapinetreatment with clozapine naturalistically administered (as per clinical guideline). |
| Treatment as usual | Active comparator | Drug: treatment as usualopen label naturalistic treatment as usual with any antipsychotic other than clozapine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClozapineAlso: clozariltreatment will occur naturalistically, as per standard clinical guidelines | Drug | Clozapine |
| treatment as usualnaturalistic treatment with any other antipsychotic medication except clozapine | Drug | Treatment as usual |
Primary outcome
Effectiveness outcome: Violent acts
Time frame: Time to violent act from randomization to treatment completion (24 weeks)
violent acts as measured by the MacArthur Community Violence Interview
Target engagement outcome: Excitement Factor of the Positive and Negative Syndrome Scale (PANSS)
Time frame: Randomization to end of study treatment (24 weeks)
a composite of the scores of excitement, uncooperativeness, poor impulse control, and hostility)
2 secondary outcomes
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2026.
Related trials for Schizophrenia
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruiting
Deep Brain Stimulation for Treatment-Resistant Schizophrenia
Treatment Resistant Disorders
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ragy Girgis, MD principal investigator
New York State Psychiatric Institute
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Clozapine and treatment as usual in people with Schizophrenia and Schizoaffective Disorder, run by New York State Psychiatric Institute at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ragy Girgis (646-774-5553, ragy.girgis@nyspi.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effectiveness outcome: Violent acts (time frame: Time to violent act from randomization to treatment completion (24 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2026.