Effect of Corneal Preservation Time on Long-Term Graft Success (CPTS)

角膜保存时间对长期移植成功率 (CPTS) 的影响

• 批准号: 8332253
• 负责人: Allison Renee Ayala
• 金额: $ 206.35万
• 依托单位: JAEB CENTER FOR HEALTH RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8332253
• 关键词: Adherence; Ancillary Study; Applications Grants; Biological Preservation; Clinical; Clinical Trials; Conduct Clinical Trials; Cornea; Coupled; Data; Data Analyses; Data Collection; Development; Endothelial Cells; Evaluation; Eye; Eye Banks; Eye diseases; FDA approved; Failure; Functional disorder; Future; Generic Drugs; Health; Image Analysis; Infection; Institutes; Institutional Review Boards; International; Internet; Keratoplasty; Laboratories; Manuscripts; Masks; Measures; Monitor; Online Systems; Operative Surgical Procedures; Pattern; Penetrating Keratoplasty; Postoperative Period; Preparation; Principal Investigator; Procedures; Process; Protocols documentation; Public Health; Publications; Quality Control; Randomized; Reading; Regulation; Research; Research Personnel; Review Committee; Robin bird; Role; Safety; Statistical Data Interpretation; Structure; System; Testing; Time; Tissue Donors; Tissues; Training; Transplantation; United States; Universities; University Hospitals; Work; abstracting; aging population; clinical research site; data management; evidence base; experience; flexibility; innovation; prospective; success; web site

DESCRIPTION (provided by applicant): After a 12% decline in the number of keratoplasties in the U.S. between 2004 and 2006 there has been a 37% increase in the number of keratoplasties in just two years. As with the Cornea Donor Study (CDS) 10 years ago, an important public health issue is again raised regarding the future adequacy of the donor pool. This recent increase has been largely driven by the advent of endothelial keratoplasty procedures which have nearly tripled, representing 33% of the keratoplasties in 2008. Coupled with a higher failure rate in the initial postoperative period than penetrating keratoplasty, an aging population with a greater number of endothelial dysfunction cases, and potential changes in the cornea evaluation process with increased regulations and more extensive laboratory testing requirements to test for emerging infections, other means to expand the donor pool besides the use of older donor tissue are needed to guarantee future supply. One major opportunity is to extend the use of donor tissue to the full FDA approved preservation time of 14 days for intermediate storage media at 40C. Corneas preserved beyond 7 days are rarely used for transplantation in the U.S. but are often exported for successful international use. While existing data do not support this bias, an evidence-based study is needed to change this practice pattern. Thus, our primary objective is to determine whether graft clarity and endothelial cell loss, the two most recognized measures of endothelial keratoplasty success, are comparable three years postoperatively for donor corneas preserved up to 7 days vs. those preserved from 8 to 14 days prior to surgery utilizing a randomized, prospective, masked clinical trial. Two separate grant applications have been submitted. The Data Management and Analysis Center (DMAC) at the Jaeb Center for Health Research, which directed the CDS, will oversee all aspects of eye bank participation in the study, multi-functional website development, data management, statistical analysis, and DSMC coordination. The Coordinating Center at Case Western Reserve University and University Hospitals Eye Institute, directed by the Study Chair, will provide scientific direction and coordination of the clinical sites and Cornea Image Analysis Reading Center activities. RELEVANCE: If longer preservation time up to the FDA limit of 14 days can be shown to not adversely impact graft success and endothelial cell loss at 3 years, more donor tissue will be available to be efficiently distributed within the United States, there will be more flexibility in time for extended testing for a suspected emerging infection, and less tissue will be exported due to exceeding a perceived limit of seven days in storage.

描述（由申请人提供）：在2004年至2006年期间，美国角膜移植术的数量下降了12%之后，仅在两年内角膜移植术的数量就增加了37%。与10年前的角膜供体研究（CDS）一样，一个重要的公共卫生问题再次提出，即未来供体库的充足性。最近的增长主要是由于内皮角膜移植术的出现，内皮角膜移植术几乎增加了两倍，占2008年角膜移植术的33%。再加上术后初期失败率高于穿透性角膜移植术，人口老龄化，内皮功能障碍病例数量增加，以及角膜评估过程中的潜在变化，法规增加和更广泛的实验室检测要求，以检测新出现的感染，除了使用较旧的供体组织外，还需要其他方法来扩大供体库，以保证未来的供应。一个主要的机会是将供体组织的使用延长到FDA批准的在40 ℃下中间储存介质的14天的完整保存时间。保存超过7天的角膜在美国很少用于移植，但经常出口用于成功的国际使用。虽然现有数据不支持这种偏见，但需要进行循证研究以改变这种做法模式。因此，我们的主要目的是通过一项随机、前瞻性、设盲的临床试验，确定移植物透明度和内皮细胞损失（内皮角膜移植术成功的两个最公认的指标）对于保存最多7天的供体角膜与手术前8 - 14天保存的供体角膜在术后3年是否具有可比性。已经提交了两份单独的赠款申请。Jaeb健康研究中心的数据管理和分析中心（DMAC）负责指导CDS，将监督眼库参与研究的各个方面，多功能网站开发，数据管理，统计分析和DSMC协调。凯斯西储大学和大学医院眼科研究所的协调中心由研究主席指导，将为临床研究中心和角膜图像分析阅读中心活动提供科学指导和协调。相关性：如果可以证明长达14天的FDA限制的更长保存时间不会对移植成功和3年时的内皮细胞损失产生不利影响，则更多的供体组织将可用于在美国境内有效分布，对于疑似新发感染的延长测试将有更大的时间灵活性，并且由于超过7天的储存限制而出口的组织将更少。