COVID Protection After Transplant (CPAT) Multicenter Adaptive Trial

实体器官移植受者因COVID-19而死亡率很高，原因是 免疫抑制和合并症。虽然SARS-CoV-2疫苗在美国非常有效， 一般人群，最近的研究表明，实体器官移植受者不太可能发展 保护性抗体反应。此外，长期的安全性研究，包括免疫后遗症， 排斥和从头供体特异性抗体形成缺乏。 我们提出了一项多中心随机自适应设计试验，以研究CPAT（COVID）的策略 移植后的保护）。这项试验将建立在200例肾移植患者CPAT试点试验的结果基础上。 研究第三剂SARS-CoV-2 mRNA疫苗在中国的安全性和免疫原性的载体。 在标准2剂量系列后未能产生高水平抗体的受者。该试验将确定关键 风险和功效的相关性。本试验将纳入这些数据，以研究其他保护策略 包括使用不同的疫苗平台和800个实体器官中免疫抑制的变化， 在15个美国移植中心中具有次优抗刺突抗体应答的移植受者。本试验 将使用贝叶斯方法对成功概率最高的候选组进行个性化随机化 框架.同时，我们将进行新的，全面的病毒学和免疫学机制的研究 以更好地了解疫苗相关免疫随时间的变化。 我们的多学科团队包括移植手术，传染病，流行病学， 生物统计学、病理学、病毒学和免疫学。我们的团队有成功注册的经验， 进行多中心移植试验（U 01 AI 134591，U 01 AI 138897），并将利用现有的 用于操作、数据管理、分析和安全报告的基础设施。 总之，本多中心适应性设计CPAT试验将确定 新的SARS-CoV-2疫苗接种策略在美国800名移植受者中。重要 机制研究将进一步从根本上了解保护性免疫反应的发展， 这个弱势群体。

Solid organ transplant recipients experience high mortality from COVID-19 due to a combination of immunosuppression and comorbidities. Although SARS-CoV-2 vaccination has been highly effective in the general population, recent studies show that solid organ transplant recipients are less likely to develop protective antibody responses. In addition, long term studies of safety, including immunologic sequela such as rejection, and de novo donor-specific antibody formation are lacking. We propose a Multicenter Randomized Adaptive Design Trial to investigate strategies for CPAT (COVID Protection After Transplant). This trial will build on results from a CPAT Pilot Trial in 200 kidney transplant reipients which will investigate the safety and immunogenicity of 3rd dose of a SARS-CoV-2 mRNA vaccines in recipients who fail to develop high level antibodies after a standard 2 dose series. That trial will identify key correlates of risk and efficacy. This trial will incorporate that data to investigate additional protective strategies including the use of different vaccine platforms and changes in immunosuppression in 800 solid organ transplant recipients with suboptimal anti-spike antibody responses across 15 US transplant centers. This trial will personalize randomization to candidate arms with the highest probability of success using a Bayesian framework. In conjuction, we will perform novel, comprehensive virologic and immunologic mechanistic studies to better understand vaccine-associated immunity over time. Our multidisciplinary team includes experts in Transplant Surgery, Infectious Diseases, Epidemiology, Biostatistics, Pathology, Virology, and Immunology. Our team has experience successfully enrolling and conducting multicenter transplantation trials (U01AI134591, U01AI138897) and will leverage existing infrastructure for operations, data management, analysis, and safety reporting. In summary, this Multicenter Adaptive Design CPAT Trial will determine the immunogenicity and safety of novel SARS-CoV-2 vaccination strategies in 800 transplant recipients across the United States. Important mechanistic studies will further fundamental understanding of development of protective immune responses in this vulnerable population.