Chiquet Christophe, Vignal Catherine, Gohier Philippe, Heron Emmanuel, Thuret Gilles, Rougier Marie Bénédicte, Lehmann Audrey, Flet Laurent, Quesada Jean-Louis, Roustit Mathieu, Milea Dan, Pepin Jean-Louis
Department of Ophthalmology, Grenoble Alpes University Hospital, 38043, Grenoble, France.
HP2 Laboratory, INSERM U1300, Grenoble Alpes University, Grenoble, France.
Trials. 2022 Oct 29;23(1):916. doi: 10.1186/s13063-022-06786-9.
Nonarteritic anterior ischemic optic neuropathy (NAAION) is a major cause of blindness in individuals over 50 years of age, with no available effective treatment. The oral dual endothelin receptor antagonist, bosentan, increases retinal optic nerve head blood flow in healthy humans and glaucoma patients. The objective of this trial is to assess the efficacy of bosentan administered at the acute stage in improving outcomes in NAAION patients.
ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy) is a phase III, interventional, prospective, multicentre, placebo-controlled randomised double-blind clinical trial. The primary outcome is change in the visual field mean deviation (MD) at 3 months (Humphrey 30-2 SITA standard programme). Secondary outcomes include MD and visual acuity changes up to 24 months, changes in peripapillary retinal nerve fibre and macular ganglion cell layer thickness in the affected eye, as measured by optical coherence tomography, rate of NAAION bilateralisation at 2 years, and quality-of-life. Patients over 50 years of age presenting with typical NAAION of recent onset (less than 21 days) are randomly assigned to either 125 mg oral bosentan or placebo, twice a day, during 8 weeks. Besides visits during the treatment phase, patients attend follow-up visits at 2, 3, 6, 12 and 24 months. The inclusion of patients began in August 2015 at five French University hospital ophthalmology departments and two specialised ophthalmology centres. It is planned to include 86 patients in this trial. To date we have included 72 patients and 49 have completed the full follow-up process.
An endothelin receptor antagonist is a potential approach to improving the anatomical and functional prognosis of patients with NAAION. This multicentre double-blind randomised controlled trial is an opportunity to assess (1) the effect of bosentan on the structure and function of the optic nerve in NAAION, at 3 months, (2) the effect of bosentan on the bilateralisation rate at 24 months and (3) the tolerance profile of bosentan in this population.
ClinicalTrials.gov NCT02377271 . Registered on March 3, 2015.
非动脉炎性前部缺血性视神经病变（NAAION）是50岁以上人群失明的主要原因，目前尚无有效的治疗方法。口服双重内皮素受体拮抗剂波生坦可增加健康人和青光眼患者视网膜视神经乳头的血流量。本试验的目的是评估急性期给予波生坦对改善NAAION患者预后的疗效。
ENDOTHELION（缺血性视神经病变中的内皮素拮抗剂受体）是一项III期、干预性、前瞻性、多中心、安慰剂对照的随机双盲临床试验。主要结局是3个月时视野平均偏差（MD）的变化（Humphrey 30-2 SITA标准程序）。次要结局包括24个月内MD和视力的变化、患眼视乳头周围视网膜神经纤维层和黄斑神经节细胞层厚度的变化（通过光学相干断层扫描测量）、2年时NAAION双眼发病的发生率以及生活质量。年龄超过50岁、近期发病（少于21天）且表现为典型NAAION的患者被随机分配至口服125 mg波生坦或安慰剂组，每天两次，持续8周。除治疗阶段的访视外，患者在2、3、6、12和24个月时进行随访。2015年8月开始在法国五所大学医院眼科和两个专业眼科中心纳入患者。本试验计划纳入86例患者。迄今为止，我们已纳入72例患者，其中49例已完成全部随访过程。
内皮素受体拮抗剂是改善NAAION患者解剖和功能预后的一种潜在方法。这项多中心双盲随机对照试验为评估（1）3个月时波生坦对NAAION患者视神经结构和功能的影响，（2）24个月时波生坦对双眼发病发生率的影响，以及（3）该人群中波生坦的耐受性提供了机会。
ClinicalTrials.gov NCT02377271。于2015年3月3日注册。
