The Safety and Efficacy of Intravitreal Topotecan for the Treatment of Proliferative Vitreoretinopathy
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 50
- 主要终点
- Recurrence of rhegmatogenous retinal detachment secondary to PVR
研究概览
简要总结
The goal of this clinical trial is to evaluate the safety and efficacy of intravitreal topotecan for the treatment of patients with rhegmatogenous retinal detachment due to proliferative vitreoretinopathy (PVR) or resulting from an open globe injury, and compare the outcomes to those who do no receive intravitreal topotecan. The main objectives it aims to achieve are:
- to study the safety profile of intravitreal topotecan in the treatment of PVR
- to evaluate the efficacy of intravitreal topotecan in treating PVR.
Post-consent, participants will:
- undergo vitrectomy (with or without scleral buckle) as part of standard treatment for retinal detachment.
- receive intravitreal topotecan at the time of surgery, post-operative day 7 and post-operative day 28 (if randomized to receive the medication)
- come in at post-operative day 1, 7, 28, 56, 84, 126 and 168 to undergo a complete ophthalmic exam along with a fundus photography and optical coherence tomography of the macula, have their intraocular pressure and visual acuity measured and their adverse events monitored, if any.
Researchers will compare participants who receive intravitreal topotecan for PVR to those who do not to see if there is a significant variability in recurrence of retinal detachment, rate of retinal reattachment and PVR grade 6 months after surgery.
详细描述
Rhegmatogenous retinal detachment (RRD) is an acute, sight-threatening condition that occurs after separation of the neurosensory retina from the underlying retinal pigment epithelium (RPE) due to the presence of a retinal break. Proliferative vitreoretinopathy (PVR) represents growth of ectopic fibrocellular growth on the surface of, within and underneath the retina. PVR is hypothesized to occur secondary to the migration of RPE cells to the peri-retina, leading to a mesenchymal transition into contractile myofibroblasts. PVR affects 5-10% of RRDs and is the most common cause of surgical failure in RRD.
Given that PVR involves a pro-inflammatory and pro-fibrotic cellular response, adjuvants such as corticosteroids and antimetabolites such as 5-fluorouracil have been attempted in the treatment of this condition. Overall, the efficacy results of these treatments have been mixed, and no standard of care adjuvant therapy has emerged.
Topotecan is a chemotherapeutic agent that acts as a topoisomerase inhibitor. It is most commonly administered intravitreally for patients with refractory or recurrent vitreous seeds from retinoblastoma, and shows high efficacy in this setting. At the same time, intravitreal topotecan administered at doses of 5-30µg has been associated with no ocular or systemic complications or adverse electroretinogram changes. To the best of available knowledge, topotecan has not been administered for the treatment of proliferative vitreoretinopathy. Topotecan has anti-inflammatory, anti-proliferative and anti-fibrotic activity that is hypothesized to exhibit high efficacy for the treatment of PVR. In this study, the efficacy and safety of intravitreal topotecan for the treatment of PVR will be investigated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients > 18 years old
- •Patients presenting with retinal detachment due with PVR (grade C or higher) or retinal detachment associated with open globe trauma
- •Patients undergoing vitrectomy or vitrectomy with scleral buckle as part of standard care.
排除标准
- •Patient unable to give consent
- •Patient unable to follow-up
- •Females of childbearing age who are pregnant at the time of recruitment. A pregnancy test will be done to all women of ages 18-55 prior to surgery to ensure they are not pregnant at the time of recruitment.
- •Patients with a history of tractional or exudative retinal detachment.
- •Patients with other planned ocular surgery following PPV
- •Active or chronic or recurrent uncontrolled ocular or systemic disease
- •Active or history of chronic or recurrent inflammatory eye disease
- •Diagnosis of severe nonproliferative or proliferative diabetic retinopathy or vasoproliferative disease in the operative eye
- •Signs of ocular infection at presentation in either eye
- •Known or suspected sensitivity or allergy to any of the medications used in the operation or postoperatively
- •No Light Perception vision in the operative eye
- •Failure to achieve intraoperative reattachment
- •Patient with silicone oil instilled in the operative eye at time of presentation
研究组 & 干预措施
Participants who received intravitreal topotecan
These are the patients who will be receiving intravitreally 20 micrograms of topotecan in a 1cc syringe during surgery, at the post-operative day 7 and at the post-operative day 28.
干预措施: Topotecan (Drug)
结局指标
主要结局
Recurrence of rhegmatogenous retinal detachment secondary to PVR
时间窗: 6 months after initial surgery, or last follow-up visit available
Investigators will be evaluating whether participant develop a recurrent retinal detachment throughout their follow up after their initial surgery.
次要结局
- Best corrected visual acuity (BCVA)(at the pre-operative assessment, and post-operative day1, 7, 28, 56, 84, 126, 168)
- Variation of PVR grade(at the pre-operative assessment, and post-operative day1, 7, 28, 56, 84, 126, 168)
- Retinal reattachment rate at month 6 or last follow up(at post-operative day 168 (or last follow-up visit available if the participant did not show up at post-operative day 168))
- Recurrence of rhegmatogenous retinal detachment due to any cause(at the pre-operative assessment, and post-operative day1, 7, 28, 56, 84, 126, 168)
- Number of participants and type of intraoperative or postoperative complications(at time of surgery, and each follow up visit (post-operative day1, 7, 28, 56, 84, 126, 168))
研究者
Leo Am Kim, M.D.
Associate Professor of Ophthalmology
Massachusetts General Hospital