A Randomized Controlled Trial of Prophylaxis with Direct-acting Antivirals for Kidney Transplantation from Hepatitis C virus-infected donor to Uninfected Recipients (PREVENT-HCV)
直接作用抗病毒药物预防丙型肝炎病毒感染供者肾移植至未感染受者的随机对照试验 (PREVENT-HCV)
基本信息
- 批准号:10597168
- 负责人:
- 金额:$ 138.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-25 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:2019-nCoVAcuteAcute Hepatitis CAdoptionAftercareAgeAgreementAlanine TransaminaseAmericanAntiviral AgentsBK VirusBiologyBiometryBloodCellsCessation of lifeCholestasisClinicalClinical ResearchCollaborationsCommunicable DiseasesCytomegalovirusDataData CollectionDoseEnrollmentEnsureEpidemiologyEquipoiseEventFailureFibrosisGeneticGenetic PolymorphismGraft SurvivalHealthHepatitisHepatitis CHepatitis C VaccineHepatitis C virusHepatocyteHourIL18 geneImmuneImmune responseImmunocompromised HostImmunologicsImmunologyIndividualInfectionInflammasomeInflammationInflammatoryInfrastructureInnate Immune ResponseInterleukin-1KidneyKidney TransplantationKnowledgeLifeLinkLiverMeasuresMediatingMonitorNephrologyNested Case-Control StudyOncologyOpioidOrganOrgan DonorOrgan TransplantationOutcomePathologyPerfusionPharmaceutical PreparationsPhylogenetic AnalysisPlasmaPrimary InfectionProphylactic treatmentRaceRandomizedRandomized, Controlled TrialsReportingResistanceSafetyShapesStandardizationSubgroupTestingTransplant RecipientsTransplantationTransplantation SurgeryTreatment FailureUncertaintyVaccinesViralViremiaVirusVirus DiseasesVirus Replicationacute liver injuryarmclinical practiceclinical riskco-infectioncytokinedata managementdonor-specific antibodyepidemic virusepidemiology studyexperienceimmune activationimprovedinnovationinsightintrahepaticlaser capture microdissectionliver biopsyliver injurymultidisciplinarynovel virusoperationopioid epidemicopioid overdosepost-transplantpreventprimary outcomesample collectionsecondary endpointsexsuccesstranscriptometransmission processtransplant centerstrial comparingvaccine developmentviral RNAviral transmissionvirologyvirome
项目摘要
Due to epidemics of opioid overdose and hepatitis C virus (HCV), the availability of kidneys from HCV-viremic
(HCV+) donors is increasing. There are limited numbers of HCV+ transplant candidates, and as a result 500-
1000 HCV+ donor kidneys are discarded each year. A new practice of HCV+ donor to HCV-naïve recipient
(HCV D+/R-) kidney transplantation (KT) with direct-acting antivirals (DAAs) has had early success. However,
there remains equipoise about whether to give DAAs as prophylaxis or as treatment post-transplant (“transmit-
and-treat”). With transmit-and-treat, HCV is cured with 8-12 weeks of DAAs, but complications such as
fibrosing cholestatic hepatitis, rejection, CMV, and BK virus are reported. Prophylaxis seems to prevent these
complications but data is limited. A direct comparison of prophylaxis and transmit-and-treat has not been done.
Determining the best strategy would allow for expansion of HCV D+/R- KT and minimize clinical complications.
We propose PREVENT HCV, a multicenter randomized controlled trial comparing DAA prophylaxis with
transmit-and-treat in HCV D+/R- KT. We will perform 120 HCV D+/R- KTs over 2 years at 6 transplant centers.
Aim 1 will compare the safety and efficacy of transmit-and-treat (SOF/VEL for 12 weeks starting day 14 post-
KT) vs prophylaxis (SOF/VEL for 2 weeks started several hours pre-KT). We will also measure clinical
complications of HCV D+/R- KT such as liver injury, rejection, and infection with these two strategies.
In this trial, the exact timing, size, and genetic composition of the transmitted viral inoculum will be known,
providing an unprecedented opportunity to study the earliest events in primary HCV infection. Leveraging this,
Aim 2 will characterize the earliest viral dynamics and phylogenetics of early HCV in the liver and blood, as
well as the transmitted virome, identifying emerging viruses, including SARsCoV2, some of which have been
implicated in rejection. Aim 3 will characterize the innate immune response to primary HCV, measuring
cytokines and the transcriptome of innate immune cells. These studies can contribute new knowledge about
HCV related to vaccine efforts and deeper understanding of the virome, generalizable beyond transplantation.
Our multidisciplinary team includes experts in Transplant Surgery, Infectious Diseases, Nephrology,
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 monitoring.
In summary, PREVENT HCV will quantify clinical risks of HCV D+/R- KT and determine the optimal DAA
approach. This could facilitate thousands of additional KTs, contributing to one of the mandates of the White
House Executive Order on American Kidney Health. Finally, this trial includes unique mechanistic studies that
can generate fundamental insights into the biology of primary HCV relevant to vaccine efforts, and knowledge
about the transmitted virome and its significance in immunocompromised hosts.
由于阿片类药物过量和丙型肝炎病毒(HCV)的流行,丙型肝炎病毒血症肾脏的可用性
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Christine Marie Durand其他文献
Christine Marie Durand的其他文献
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{{ truncateString('Christine Marie Durand', 18)}}的其他基金
Kidney Transplantation from Donors with HIV: Impact on Rejection and Long-term Outcomes
艾滋病毒捐献者的肾移植:对排斥和长期结果的影响
- 批准号:
10704333 - 财政年份:2023
- 资助金额:
$ 138.95万 - 项目类别:
A Randomized Controlled Trial of Prophylaxis with Direct-acting Antivirals for Kidney Transplantation from Hepatitis C virus-infected donor to Uninfected Recipients (PREVENT-HCV)
直接作用抗病毒药物预防丙型肝炎病毒感染供者肾移植至未感染受者的随机对照试验 (PREVENT-HCV)
- 批准号:
10405358 - 财政年份:2022
- 资助金额:
$ 138.95万 - 项目类别:
HOPE in Action: A Clinical Trial of HIV-to-HIV Liver Transplantation
希望在行动:HIV 至 HIV 肝移植的临床试验
- 批准号:
10492082 - 财政年份:2021
- 资助金额:
$ 138.95万 - 项目类别:
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 - 财政年份:2021
- 资助金额:
$ 138.95万 - 项目类别:
HOPE in Action: A clinical trial of HIV-to-HIV deceased donor kidney transplantation
希望在行动:艾滋病毒转艾滋病毒死者供体肾移植的临床试验
- 批准号:
10462020 - 财政年份:2021
- 资助金额:
$ 138.95万 - 项目类别:
HOPE in Action: A Clinical Trial of HIV-to-HIV Liver Transplantation
希望在行动:HIV 至 HIV 肝移植的临床试验
- 批准号:
10214504 - 财政年份:2018
- 资助金额:
$ 138.95万 - 项目类别:
HOPE in Action: A Clinical Trial of HIV-to-HIV Liver Transplantation
希望在行动:HIV 至 HIV 肝移植的临床试验
- 批准号:
9753122 - 财政年份:2018
- 资助金额:
$ 138.95万 - 项目类别:
HOPE in Action: A Clinical Trial of HIV-to-HIV Liver Transplantation
希望在行动:HIV 至 HIV 肝移植的临床试验
- 批准号:
10459319 - 财政年份:2018
- 资助金额:
$ 138.95万 - 项目类别:
HOPE in Action: A Clinical Trial of HIV-to-HIV Liver Transplantation
希望在行动:HIV 至 HIV 肝移植的临床试验
- 批准号:
10622648 - 财政年份:2018
- 资助金额:
$ 138.95万 - 项目类别:
HOPE in Action: A Clinical Trial of HIV-to-HIV Liver Transplantation
希望在行动:HIV 至 HIV 肝移植的临床试验
- 批准号:
10681594 - 财政年份:2018
- 资助金额:
$ 138.95万 - 项目类别:
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