Clarifying the Optimal Application of SLT Therapy (COAST) Trial

阐明 SLT 疗法 (COAST) 试验的最佳应用

• 批准号: 10698062
• 负责人: Balasubramani K Goundappa
• 金额: $ 276.92万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10698062
• 关键词: Adherence; Argon; Cell physiology; Cells; Clinical Research; Complex; Cornea; Data; Data Set; Development; Dose; Drops; Effectiveness; Eye; Face; Failure; Free Will; Freedom; Glaucoma; Goals; Health; Human; Impairment; Inflammation; Italy; Laser Surgery; Lasers; Light; Longevity; Maintenance; Medical; Molecular; Multi-Institutional Clinical Trial; Newly Diagnosed; Ocular Hypertension; Open-Angle Glaucoma; Operative Surgical Procedures; Outcome; Participant; Patients; Pattern; Pharmaceutical Preparations; Physiologic Intraocular Pressure; Process; Protocols documentation; Randomized; Regimen; Retreatment; Safety; Series; Shapes; Site; Specific qualifier value; Spottings; Survival Rate; Synthetic Prostaglandins; System; Therapy trial; Time; Titrations; Trabecular meshwork structure; Trabeculectomy; Vision; aqueous; comparative efficacy; compliance behavior; design; disorder control; follow-up; glaucoma surgery; high risk; minimally invasive; novel therapeutics; preservation; prevent; primary outcome; procedure safety; randomized trial; randomized, clinical trials; response; tissue culture; treatment strategy

COAST Abstract Open-angle glaucoma (OAG) is managed primarily with topical medical therapy, with laser and surgical interventions reserved for those in whom medical therapy is ineffective, intolerable, or inappropriate. The effectiveness of medical therapy is limited by patient adherence with therapy; inadequate adherence has been extensively documented. Selective laser trabeculoplasty (SLT) has comparable efficacy to preferred first-line prostaglandin analogues, is very safe, and obviates the need for daily medical therapy in most patients when applied as primary therapy. A recent randomized trial demonstrated superior glaucoma outcomes (less progression, fewer surgeries required) in newly diagnosed OAG patients receiving primary SLT vs. medical therapy, providing the evidentiary basis for a paradigm shift that is already underway in which SLT supplants medical therapy as the preferred first-line treatment for OAG. SLT is largely performed as first described by its inventor; little exploration of dose-response has been undertaken. An intriguing data set from Italy (with significant weaknesses and limitations) suggests that low energy SLT repeated annually is far more effective than standard SLT repeated as needed when its effect wanes, in delaying or preventing the need for topical medical therapy. This finding is consistent with the limited data exploring the dose-response relationship between SLT and intraocular pressure (IOP) reduction. Further, it is biologically plausible that ongoing health maintenance of trabecular meshwork (TM) function with proactive annual low energy SLT would better preserve the TM's long-term health and function than a repeated cycle of SLT, progressive TM re-impairment by the glaucoma process, loss of IOP control, and repeat SLT. Our proposal describes a multi-center clinical trial to answer two key questions: 1) Is primary low energy SLT as effective as primary standard energy SLT in newly diagnosed and treatment-naïve patients with mild-moderate OAH or high-risk ocular hypertension?; and 2) Does annual low energy repeat SLT more effectively delay or prevent the need for medical therapy compared to standard SLT repeated as needed when its effect wanes and IOP rises? Participants will be randomized to initial standard SLT or initial low energy SLT with the possibility of a single repeat SLT as needed in the first year of the study. The first primary outcome will be 12-month survival where failure represents the need for repeat SLT to achieve/maintain protocol-specified target IOP. At Month 12, all participants who remain medication-free will be re-randomized to undergo repeat SLT either as needed when IOP exceeds target IOP (at initially randomized energy) or to annual low energy SLT irrespective of IOP. The second primary outcome will be 42-month medication-free survival in subjects who were medication-free at Month 12. Our study seeks to clarify the optimal way to utilize SLT with the ultimate goal of maximizing long- term SLT responsiveness and medication-free survival. If successful, our results will shape the course of treatment for most newly diagnosed and treatment-naïve patients with mild-moderate OAG or high-risk OHT.

COAST摘要 开角型青光眼（OAG）主要通过局部药物治疗、激光和手术治疗来治疗。 为那些药物治疗无效、无法忍受或不适当的人保留的干预措施。的 药物治疗的有效性受到患者对治疗的依从性的限制; 广泛记录。选择性激光小梁成形术（LASIK）的疗效与首选的一线小梁成形术相当。 前列腺素类似物，是非常安全的，并避免了日常药物治疗的需要，在大多数患者， 作为主要治疗。最近的一项随机试验表明，上级青光眼的结果（少 进展，需要较少的手术）相比， 治疗，为已经在进行的范式转变提供证据基础， 药物治疗作为OAG首选的一线治疗。它主要是按照其最初的描述进行的， 发明人;很少探索剂量反应已进行。来自意大利的一组有趣的数据（ 显著的弱点和局限性）表明，每年重复的低能量训练更有效 当其效果减弱时，根据需要重复的标准药物，在延迟或预防局部用药的需要方面， 药物治疗这一发现与探索剂量-反应关系的有限数据一致 眼内压（IOP）降低与眼内压（IOP）降低之间的关系。此外，从生物学上讲，持续的健康 保持小梁网（TM）的功能，积极每年低能量饮食会更好 保持TM的长期健康和功能，而不是反复循环的渐进性TM再损伤 通过青光眼过程，IOP控制的丧失，以及重复眼压。我们的建议描述了一个多中心的临床 试验回答了两个关键问题：1）初级低能量转换是否与初级标准能量转换一样有效？ 轻中度OAH或高风险高眼压的新诊断和初治患者？;和 2)每年低能量重复治疗是否能更有效地延迟或预防药物治疗的需要 与当其作用减弱和IOP升高时根据需要重复的标准眼压计相比？参与者将被 随机分配至初始标准剂量组或初始低能量剂量组，可能为单次重复剂量组 在研究的第一年，第一个主要结局是12个月生存率， 表示需要重复IOP以达到/维持方案规定的目标IOP。在第12个月，所有 保持无药物治疗的受试者将被重新随机化，根据需要进行重复给药， IOP超过目标IOP（在初始随机能量下）或超过年度低能量范围，无论IOP如何。的 第二个主要结局将是42个月无药物治疗的受试者的无药物治疗生存期， 第12个月。我们的研究旨在阐明最佳的方式来利用可再生能源的最终目标，最大限度地延长， 长期免疫反应性和无药生存率。如果成功，我们的成果将塑造 治疗大多数新诊断和初治的轻中度OAG或高危OHT患者。