Unidad de Investigación Clinica y Ensayos Clínicos, Hospital Clínico San Carlos, IdISSC, Madrid, Spain.
Departamento de Enfermería. Facultad Enfermería, Fisioterapia y Podología, Universidad Complutense de Madrid, Madrid, Spain.
BMJ Open. 2022 Mar 22;12(3):e051378. doi: 10.1136/bmjopen-2021-051378.
Non-infectious uveitis include a heterogeneous group of sight-threatening and incapacitating conditions. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), prescribed in monotherapy or in combination. Several observational studies showed that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet.
The Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicentre, prospective, randomised, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis. We aim to recruit 192 subjects. The duration of the treatment and follow-up will last up to 52 weeks, plus 70 days follow-up with no treatment. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secondary measurements of efficacy (quality of life, visual acuity and costs) and safety, we will identify subjects' subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers.
The protocol, annexes and informed consent forms were approved by the Reference Clinical Research Ethic Committee at the Hospital Clínico San Carlos (Madrid, Spain) and the Spanish Agency for Medicines and Health Products. We will elaborate a dissemination plan including production of materials adapted to several formats to communicate the clinical trial progress and findings to a broad group of stakeholders. The promoter will be the only access to the participant-level data, although it can be shared within the legal situation.
2020-000130-18; NCT04798755.
非感染性葡萄膜炎包括一组具有异质性的、可导致视力丧失和致残的疾病。为了正确治疗这些疾病，有时需要使用免疫抑制剂（ISD）进行单药或联合治疗。多项观察性研究表明，联合使用 ISD 比单药治疗更有效且安全。然而，这两种治疗策略之间尚未进行直接比较。
组合疗法治疗葡萄膜炎的疗效、安全性和成本效益评价（CoTHEIA）研究是一项多中心、前瞻性、随机、单盲、以安慰剂为对照、三臂平行的 III 期临床试验，采用 1:1:1 随机分组，比较甲氨蝶呤、阿达木单抗或两者联合治疗非感染性非前部葡萄膜炎的疗效、安全性和成本效益。我们的目标是招募 192 名受试者。治疗和随访时间最长可达 52 周，无治疗随访期为 70 天。盲法评估员将评估眼部炎症的完全缓解和持续缓解（主要结局）。除其他次要疗效（生活质量、视力和成本）和安全性测量外，我们还将通过使用遗传和蛋白质组学生物标志物开发基于机器学习技术的预测模型，确定具有不同治疗反应的患者亚组。
该方案、附件和知情同意书已获得马德里圣卡洛斯临床医院（西班牙）参考临床研究伦理委员会和西班牙药品和医疗产品管理局的批准。我们将制定一个传播计划，包括制作多种格式的材料，向广大利益相关者通报临床试验进展和发现。申办方将是唯一可以访问参与者水平数据的人，尽管可以在法律规定的情况下共享数据。
2020-000130-18；NCT04798755。
