Evidence map›Paper›PMID 38355533›Full record

ArticleBMC psychiatry2024

CLEAR - clozapine in early psychosis: study protocol for a multi-centre, randomised controlled trial of clozapine vs other antipsychotics for young people with treatment resistant schizophrenia in real world settings.

C Casetta, P Santosh, R Bayley, J Bisson, S Byford, C Dixon, R J Drake, R Elvins, R Emsley, N Fung and 15 more

Open access · goldAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. An etiological approach to psychosis: potential benefits for treatment, research and prevention.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2026
    Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 10 institutions in 1 country.

C CasettaInstitute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. cecilia.casetta@kcl.ac.uk.
P SantoshInstitute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
R BayleyInstitute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
J BissonDivision of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
S ByfordInstitute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
C DixonWonford House Hospital, Devon Partnership NHS Trust, Exeter, UK.
R J DrakeDivision of Psychology & Mental Health, University of Manchester, Manchester, UK.
R ElvinsManchester University Hospitals NHS Foundation Trust, Manchester, UK.
R EmsleyInstitute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
N FungBirmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
D HayesSouth London and Maudsley NHS Foundation Trust, London, UK.
O HowesInstitute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
A JamesDepartment of Psychiatry, University of Oxford, Oxford, UK.
K JamesInstitute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
R JonesBirmingham and Solihull Mental Health Foundation Trust, Birmingham, UK.
H KillaspyDivision of Psychiatry, University College London, London, UK.
B LennoxDepartment of Psychiatry, University of Oxford, Oxford, UK.
L MarchantInstitute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
P McGuireDepartment of Psychiatry, University of Oxford, Oxford, UK.
E OloyedeInstitute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
M RogdakiInstitute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
R UpthegroveInstitute for Mental Health, University of Birmingham, Birmingham, UK.
J WaltersDivision of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
A Egerton *Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
J H MacCabe *Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
King's College London · GBUniversity of Oxford · GBCardiff University · GBSouth London and Maudsley NHS Foundation Trust · GBBirmingham and Solihull Mental Health NHS Foundation Trust · GBBirmingham Women’s and Children’s NHS Foundation Trust · GBDevon Partnership NHS Trust · GBUniversity College London · GBUniversity of Birmingham · GBUniversity of Manchester · GB

Funding

Medical Research Council MR/J012939/1Medical Research Council MR/N019067/1
6 · The paper itself

Abstract

backgroundClozapine is an antipsychotic drug with unique efficacy, and it is the only recommended treatment for treatment-resistant schizophrenia (TRS: failure to respond to at least two different antipsychotics). However, clozapine is also associated with a range of adverse effects which restrict its use, including blood dyscrasias, for which haematological monitoring is required. As treatment resistance is recognised earlier in the illness, the question of whether clozapine should be prescribed in children and young people is increasingly important. However, most research to date has been in older, chronic patients, and evidence regarding the efficacy and safety of clozapine in people under age 25 is lacking. The CLEAR (CLozapine in EARly psychosis) trial will assess whether clozapine is more effective than treatment as usual (TAU), at the level of clinical symptoms, patient rated outcomes, quality of life and cost-effectiveness in people below 25 years of age. Additionally, a nested biomarker study will investigate the mechanisms of action of clozapine compared to TAU. METHODS AND

designThis is the protocol of a multi-centre, open label, blind-rated, randomised controlled effectiveness trial of clozapine vs TAU (any other oral antipsychotic monotherapy licenced in the British National Formulary) for 12 weeks in 260 children and young people with TRS (12-24 years old). AIM AND

objectivesThe primary outcome is the change in blind-rated Positive and Negative Syndrome Scale scores at 12 weeks from baseline. Secondary outcomes include blind-rated Clinical Global Impression, patient-rated outcomes, quality of life, adverse effects, and treatment adherence. Patients will be followed up for 12 months and will be invited to give consent for longer term follow-up using clinical records and potential re-contact for further research. For mechanism of action, change in brain magnetic resonance imaging (MRI) biomarkers and peripheral inflammatory markers will be measured over 12 weeks. DISCUSSION: The CLEAR trial will contribute knowledge on clozapine effectiveness, safety and cost-effectiveness compared to standard antipsychotics in young people with TRS, and the results may guide future clinical treatment recommendation for early psychosis.

trial registrationISRCTN Number: 37176025, IRAS Number: 1004947. TRIAL STATUS: In set-up. Protocol version 4.0 01/08/23. Current up to date protocol available here: https://fundingawards.nihr.ac.uk/award/NIHR131175# /.

Indexed as

Antipsychotic AgentsClozapinePsychotic DisordersSchizophreniaAdolescentAdultAgedChildHumansMulticenter Studies as TopicQuality of LifeRandomized Controlled Trials as TopicSchizophrenia, Treatment-ResistantYoung AdultAntipsychotic AgentsClozapineChildren and young peopleClinical trialClozapineEarly onset schizophreniaTreatment resistant psychosis

Identifiers

PMID38355533
PMCPMC10865566
OpenAlexW4391813513

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.