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Clarifying the Optimal Application of SLT Therapy (COAST) Trial

阐明 SLT 疗法 (COAST) 试验的最佳应用

基本信息

批准号：
10022560
负责人：
Balasubramani K Goundappa
金额：
$ 178.86万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
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/10022560
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

项目摘要

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、激光和手术治疗为那些药物治疗无效、无法耐受或不适当的患者保留的干预措施。这药物治疗的有效性受到患者治疗依从性的限制；依从性不够广泛记录。选择性激光小梁成形术 (SLT) 的疗效与首选一线疗法相当前列腺素类似物非常安全，并且大多数患者无需进行日常药物治疗用作主要治疗。最近的一项随机试验表明，青光眼的治疗效果较好（较少与接受传统 SLT 治疗的新诊断 OAG 患者相比，接受初次 SLT 治疗的 OAG 患者病情进展、所需手术更少疗法，为已经开始的范式转变（SLT 取代 SLT）提供证据基础药物治疗作为 OAG 的首选一线治疗。 SLT 很大程度上按照其最初描述的方式执行发明者;对剂量反应的探索很少。来自意大利的有趣数据集（显着的弱点和局限性）表明每年重复的低能量 SLT 更为有效比标准 SLT 在其效果减弱时根据需要重复进行，可以延迟或防止局部用药的需要药物治疗。这一发现与探索剂量反应关系的有限数据一致 SLT 和眼压 (IOP) 降低之间的关系。此外，持续的健康在生物学上是合理的通过主动每年低能量 SLT 来维护小梁网 (TM) 功能会更好与重复的 SLT 周期（渐进性 TM 重新损伤）相比，可以保持 TM 的长期健康和功能青光眼过程、眼压控制丧失和重复 SLT。我们的提案描述了多中心临床尝试回答两个关键问题：1) 初级低能 SLT 是否与初级标准能源 SLT 一样有效？新诊断和未接受过治疗的轻中度 OAH 或高危高眼压患者？和 2) 每年低能量重复 SLT 是否能更有效地延迟或避免药物治疗的需要与标准 SLT 相比，当其效果减弱且 IOP 上升时，根据需要重复？参加者将是随机分配到初始标准 SLT 或初始低能量 SLT，并可能进行单次重复 SLT 学习第一年需要。第一个主要结果将是 12 个月的生存率，其中失败表示需要重复 SLT 来实现/维持协议指定的目标 IOP。第 12 个月时，所有保持不服药的参与者将根据需要重新随机接受重复 SLT IOP 超过目标 IOP（在初始随机能量下）或达到年度低能量 SLT，无论 IOP 如何。这第二个主要结局是在 2019 年未接受药物治疗的受试者的 42 个月无药物生存期。第 12 个月。我们的研究旨在阐明利用 SLT 的最佳方式，最终目标是最大化长期收益术语 SLT 反应性和无药物生存期。如果成功，我们的结果将决定整个过程为大多数新诊断和初治的轻中度 OAG 或高危 OHT 患者提供治疗。