Evaluation of Dextenza in Patients With Ocular Graft Vs Host Disease (GVHD) and Effect on Ocular Surface Disease Outcomes.
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Symptomatic Relief
研究概览
简要总结
To evaluate the safety and efficacy of Dextenza intracanalicular insert in patients with ocular graft-versus-host disease (GVHD).
详细描述
Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a curative, established treatment modality for a variety of malignant and nonmalignant hematologic disorders. Despite an increase in patient survival with HSCT, Graft-Versus-Host Disease (GVHD), in which donor immune cells detect recipient cells as foreign and attack the host tissue, is associated with significant morbidity and mortality after allo-HSCT. Ocular surface involvement is one of the most common manifestations of chronic GVHD with up to 60-90% of patients affected. Dry eye (DE) is the typical finding in ocular GVHD, and severe, chronic inflammation plays a crucial role in the pathogenesis. Therefore, topical steroids have been commonly used in patients with ocular GVHD (oGVHD). Although a healing effect of topical steroids has been shown in oGVHD, the efficacy of treatment might be reduced if it is not applied appropriately; poor patient compliance and improper drop administration (such as missing the eye and instilling an insufficient amount of medication) might diminish medication efficacy. Additionally, even if drops are applied appropriately, only approximately 5% of the administered dose can reach the target tissue because of blinking, nasolacrimal drainage, and low corneal permeability. Furthermore, the intermittent administration of topical drops results in a variable drug concentration in the target tissue and produces a suboptimal pharmacologic effect. Additionally, the prolonged use of topical steroids can also be toxic to the ocular surface due to preservatives such as benzalkonium chloride, which is used for its anti-microbial properties to prevent the contamination of drops. This toxicity might further disrupt the corneal epithelial barrier, which is already disrupted because of existing ocular surface inflammation.
To address all of these obstacles associated with topical steroids in patients with oGVHD, a sustained-released preservative-free intracanalicular insert (Dextenza, Ocular Therapeutix) may be beneficial. The purpose of this clinical trial is evaluate the safety and efficacy of Dextenza intracanalicular inserts in patients with ocular GVHD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
The randomization results will also be communicated to the treating physician, who will administer the Dextenza and control plug in the respective eyes while keeping the patient blinded.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients diagnosed as chronic ocular GVHD
- •Age >= 18 years
- •Corneal Fluorescein Staining ≥ 4
- •Ocular Surface Disease Index ≥22.
排除标准
- •History of immune diseases other than GVHD, herpetic keratitis or ocular malignancy
- •Treatment regimen changes with topical cyclosporine, autologous serum, anakinra, or oral tetracycline compounds within 30 days prior to enrollment;
- •Treatment regimen changes with systemic immunosuppressants or topical anti-glaucoma medications within 15 days prior to enrollment
- •Current use of topical steroids more than twice a day
- •Current or history of steroid induced ocular hypertension or glaucoma
- •Family history of steroid induced ocular hypertension or glaucoma
- •History of any intra-ocular surgery in the past 3 months or contact lens use within 2 weeks prior to enrollment
- •History of collagen (prolong) intra-canalicular plug within 6 months
- •Inability to cooperate for a comprehensive ocular examination
- •History of lid deformity or neuroparalytic lid disease
- •Active ocular infection including herpetic disease
研究组 & 干预措施
DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg, for intracanalicular use
All patients will receive Dextenza insert in one eye and a regular dissolvable intracanalicular plug in the fellow-eye (randomized).
干预措施: DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg, for intracanalicular use (Drug)
Dissolvable intracanalicular plug
All patients will receive Dextenza insert in one eye and a regular dissolvable intracanalicular plug in the fellow-eye (randomized).
干预措施: Regular dissolvable intracanalicular plug (Device)
结局指标
主要结局
Symptomatic Relief
时间窗: 4 Weeks
The difference in symptomatic relief from baseline to 4 weeks, as compared to the contralateral eye using The Symptom Assessment Questionnaire iN Dry Eye Questionnaire (SANDE). SANDE is a visual analog scale questionnaire that quantifies the severity and frequency of dry eye symptoms. Subjects mark on a 100 mm horizontal linear visual analog scale, with a pen or pencil, their frequency, and severity. By measuring, in mm, where each scale was marked, a score can be obtained, from 0 to 100, where a higher score correlates to more frequent and more severe symptoms.
Lissamine green staining score
时间窗: 4 Weeks
The difference in the reduction of lissamine green staining compared to the contralateral eye. Six regions are graded for each eye (3 nasal conjunctival regions and 3 temporal conjunctival regions) from 0-3. Thus, a maximum score of 18 is possible for each eye. A higher score correlates to higher severity.
Corneal Fluorescein Staining Score
时间窗: 4 weeks
Difference in the reduction of corneal fluorescein staining (CFS) compared to the contralateral eye. The cornea is divided into five zones (central, superior, temporal, nasal, and inferior) and for each zone, the severity of corneal fluorescein staining is graded on a scale from 0 to 3. Therefore, the maximum score is 15 for each eye. A higher score correlates to higher severity.
次要结局
- Schirmer's Test(8 Weeks)
- Tear Break Up Time(8 Weeks)
- The Symptom Assessment Questionnaire iN Dry Eye Questionnaire(8 Weeks)
研究者
Reza Dana, MD
Professor, Director of Epidemiology for Ophthalmology
Massachusetts Eye and Ear Infirmary