COVID Protection After Transplant (CPAT) Multicenter Adaptive Trial

移植后新冠肺炎保护 (CPAT) 多中心适应性试验

• 批准号: 10457200
• 负责人: Christine Marie Durand
• 金额: $ 694.18万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10457200
• 关键词: 2019-nCoV; Acute; Adenovirus Vector; Adjuvant; Antibodies; Antibody Formation; Antibody Response; Antigens; Antimetabolites; Avidity; B-Lymphocyte Subsets; Bayesian Modeling; Biological Assay; Biometry; CD8-Positive T-Lymphocytes; COVID-19; COVID-19 mortality; COVID-19 pandemic; COVID-19 vaccination; COVID-19 vaccine; Cellular Immunity; Coupled; Data; Development; Diabetes Mellitus; Dose; Effectiveness; Enrollment; Epitopes; Event; Flow Cytometry; Functional disorder; Futility; General Population; Goals; Heart; Humoral Immunities; Immune response; Immunity; Immunocompetent; Immunodominant Epitopes; Immunoglobulin Class Switching; Immunologic Memory; Immunologics; Immunology; Immunophenotyping; Immunosuppression; Infection; Infectious Disease Epidemiology; Infrastructure; Intervention; Kidney; Kidney Transplantation; Libraries; Liver; Longitudinal Studies; Lung; Memory B-Lymphocyte; Messenger RNA; Metabolic; Monitor; Multi-Institutional Clinical Trial; Organ; Organ Transplantation; Pathology; Patients; Peptides; Persons; Phenotype; Pilot Projects; Population; Probability; Prospective cohort; RNA vaccine; Randomized; Reaction; Reporting; Risk; Route; Safety; Secondary Immunization; Series; Solid; Speed; Stains; T cell receptor repertoire sequencing; T cell response; Technology; Time; Transplant Recipients; Transplantation; Transplantation Surgery; United States; Vaccinated; Vaccination; Vaccine Antigen; Vaccines; Virus; Virus-like particle; Vulnerable Populations; antigen-specific T cells; arm; comorbidity; coronavirus disease; data management; design; donor-specific antibody; enzyme linked immunospot assay; experience; follow-up; immunogenic; immunogenicity; immunoregulation; improved; interest; mortality; multidisciplinary; novel; older patient; operation; pilot trial; programs; response; safety study; single-cell RNA sequencing; success; transplant centers; treatment arm; trial design; vaccination strategy; vaccine safety; vaccine trial; variants of concern; virology

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.

实体器官移植受者因COVID-19死亡率很高，原因是