Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
South London and Maudsley NHS Foundation Trust, London, UK.
BMC Psychiatry. 2024 Feb 14;24(1):122. doi: 10.1186/s12888-023-05397-1.
Clozapine 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.
This 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).
The 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.
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.
ISRCTN Number: 37176025, IRAS Number: 1004947.
In set-up. Protocol version 4.0 01/08/23. Current up to date protocol available here: https://fundingawards.nihr.ac.uk/award/NIHR131175# /.
氯氮平是一种具有独特疗效的抗精神病药物，是治疗难治性精神分裂症（TRS：对至少两种不同的抗精神病药物无反应）的唯一推荐治疗方法。然而，氯氮平也与一系列不良反应有关，限制了其使用，包括血液疾病，需要进行血液学监测。由于治疗抵抗在疾病早期就已被认识到，因此氯氮平是否应在儿童和青少年中开处方的问题变得越来越重要。然而，迄今为止，大多数研究都集中在年龄较大的慢性患者身上，缺乏关于 25 岁以下人群氯氮平的疗效和安全性的证据。CLEAR（早期精神病中的氯氮平）试验将评估氯氮平是否比常规治疗（TAU）更有效，在临床症状、患者自评结果、生活质量和成本效益方面，在 25 岁以下人群中。此外，一项嵌套的生物标志物研究将比较氯氮平与 TAU 的作用机制。
这是一项多中心、开放标签、盲评、随机对照有效性试验的方案，评估氯氮平与 TAU（英国国家处方集许可的任何其他口服抗精神病单药治疗）在 260 名 TRS（12-24 岁）儿童和青少年中治疗 12 周的疗效。
主要结局是从基线到 12 周时盲评阳性和阴性综合征量表评分的变化。次要结局包括盲评临床总体印象、患者自评结果、生活质量、不良反应和治疗依从性。患者将接受 12 个月的随访，并邀请他们通过临床记录和潜在的重新联系进行更长期的随访，以进行进一步的研究。对于作用机制，将在 12 周内测量脑磁共振成像（MRI）生物标志物和外周炎症标志物的变化。
CLEAR 试验将提供关于氯氮平在 TRS 年轻患者中与标准抗精神病药物相比的疗效、安全性和成本效益的知识，结果可能为早期精神病的未来临床治疗建议提供指导。
ISRCTN 编号：37176025，IRAS 编号：1004947。
正在设置中。协议版本 4.0 01/08/23。最新的当前协议可在此处获得：https://fundingawards.nihr.ac.uk/award/NIHR131175#/。
