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: 10252905
• 负责人: Balasubramani K Goundappa
• 金额: $ 265.75万
• 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/10252905
• 关键词: Adherence; Argon; Biological; 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; Randomized Clinical Trials; Regimen; Retreatment; Safety; Series; Shapes; Site; Specific qualifier value; Spike Potential; Spottings; Survival Rate; Synthetic Prostaglandins; System; Therapy trial; Time; 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; 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.

海岸摘要 开角型青光眼(OAG)主要通过局部药物治疗、激光治疗和手术治疗。 为那些药物治疗无效、无法忍受或不合适的人而保留的干预措施。这个 药物治疗的有效性受到患者坚持治疗的限制；坚持治疗的力度不够 大量记录在案。选择性激光小梁成形术(SLT)的疗效与首选一线手术相当 前列腺素类似物，非常安全，大多数患者在以下情况下不需要日常药物治疗 将其作为主要治疗方法。最近的一项随机试验显示，青光眼的结果更好(更少 进展，需要更少的手术)接受原发SLT的新诊断OAG患者与接受内科治疗的患者相比 治疗，为已经在进行的SLT替代的范式转变提供了证据基础 药物治疗是OAG首选的一线治疗方法。SLT在很大程度上按照其最先描述的方式执行 发明家；对剂量反应的探索很少。来自意大利的耐人寻味的数据集(包括 明显的弱点和局限性)表明每年重复的低能量SLT要有效得多 比标准SLT在其效果减弱时根据需要重复，在延迟或防止局部应用的需要方面 药物治疗。这一发现与探索剂量-反应关系的有限数据是一致的 SLT与降低眼压之间的关系。此外，从生物学上讲，目前的健康状况 积极的年度低能量SLT能更好地维持小梁网(TM)的功能 保护TM的长期健康和功能胜过反复循环的SLT，进行性TM再损害 受青光眼进程影响，眼压失控，反复进行SLT。我们的提案描述了一个多中心的临床 尝试回答两个关键问题：1)初级低能量SLT与初级标准能量SLT在 新诊断和治疗-患有轻中度OAH或高危高眼压的幼稚患者？；以及 2)每年的低能量重复SLT是否能更有效地延缓或预防药物治疗的需要 与标准的SLT相比，当其效果减弱和眼压上升时，根据需要重复进行？参与者将是 随机到初始标准SLT或初始低能量SLT，单次重复SLT的可能性为 在研究的第一年需要。第一个主要结果将是在失败的情况下存活12个月 表示需要重复SLT以达到/保持协议指定的目标IOP。在12个月时，所有人 保持无药物治疗的参与者将被重新随机分组，以接受重复的SLT，当需要时 眼压超过目标眼压(初始随机能量)或达到年度低能量SLT，而不考虑眼压。这个 第二个主要结果将是无药物治疗的受试者的42个月无药物生存。 12个月。我们的研究试图阐明利用SLT的最佳方式，最终目标是最大化长期- SLT反应性与非用药生存期。如果成功，我们的结果将决定 治疗大多数新诊断和治疗幼稚的轻、中度OAG或高危OHT患者。