1/2 Ganciclovir to Prevent Reactivation of Cytomegalovirus in Patients with Acute Respiratory Failure and Sepsis
1/2 更昔洛韦预防急性呼吸衰竭和脓毒症患者巨细胞病毒再激活
基本信息
- 批准号:10701856
- 负责人:
- 金额:$ 212.01万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-16 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAcute respiratory failureAdmission activityAdultAgeAnimal ModelAntiviral AgentsAreaCaringClinicalClinical TrialsCollaborationsCritical IllnessCytomegalovirusCytomegalovirus InfectionsData AnalysesData Coordinating CenterDiseaseDouble-Blind MethodEnrollmentEventExposure toFunctional disorderFundingGanciclovirGenderGrantHealth ExpendituresHerpesviridaeHospitalizationHourHumanImmunocompetentImmunocompromised HostIncidenceInfrastructureInterventionIntervention StudiesInvestigationKineticsLength of StayLungLymphocyte CountMeasuresMechanical ventilationMorbidity - disease rateMulti-Institutional Clinical TrialNational Heart, Lung, and Blood InstituteNatureObservational StudyOrganOutcomePatient CarePatient RecruitmentsPatient-Focused OutcomesPatientsPersonsPhasePlasmaPopulationPositioning AttributePredictive FactorPreventionProphylactic treatmentPublishingRaceRandomizedRecoveryResearchResearch DesignRespiratory FailureRespiratory SystemSafetySepsisSeverity of illnessSiteSurvivorsTestingTimeVentilatorViral Load resultVirusVirus Replicationadverse outcomecell typeclinical practiceclinical research siteclinically relevantcomorbidityexperienceimprovedimproved outcomeinsightlung injurymortalitypharmacologicpreventrandomized placebo controlled trialsecondary outcomeseropositivetrendvirology
项目摘要
PROJECT SUMMARY
Sepsis-associated acute respiratory failure is a leading cause of morbidity, mortality and health care expenditure
world-wide, and is increasing in incidence. Despite intensive investigation, there are few pharmacologic
interventions, and care is largely supportive. Cytomegalovirus (CMV) is a human herpesvirus that infects 50-
80% of healthy adults and establishes lifelong latency in the lung, generally causing overt disease only in
severely immunosuppressed patients. CMV reactivation (viral replication) from latency occurs in ~40% of CMV
seropositive, otherwise immunocompetent persons during critical illness and is associated with worse clinical
outcomes including increased mortality, prolonged mechanical ventilation, and increased ICU length of stay.
Compelling evidence implicating CMV reactivation as a causal contributor to morbidity and mortality in sepsis-
associated respiratory failure comes from animal models and our recently completed NHLBI-funded phase 2
randomized placebo-controlled trial (RCT) of ganciclovir prophylaxis. In this trial, among CMV seropositive adults
with sepsis-associated respiratory failure, ganciclovir effectively suppressed CMV replication, had an acceptable
safety profile, and was associated with improved clinical outcomes, including increased ventilator-free days
(VFD), shorter duration of mechanical ventilation among survivors, shorter ICU length of stay, and improved
PaO2/FiO2 ratio in day-7 survivors. We hypothesize that IV ganciclovir administered early in critical illness will
effectively suppress CMV reactivation in CMV seropositive adults with sepsis-associated acute respiratory
failure, thereby reducing lung damage, accelerating recovery, and leading to improved clinical outcomes.
We propose to conduct a phase 3 RCT to determine whether the antiviral drug ganciclovir given as prophylaxis
improves VFDs and other clinically relevant outcomes when administered within 5 days of ICU admission to
CMV seropositive immunocompetent adults with sepsis-associated acute respiratory failure. We will measure
the effect of the study intervention on the primary trial outcome (VFDs) and secondary outcomes (mortality at 28
days, duration of mechanical ventilation in survivors, oxygenation, static respiratory system compliance, CMV
plasma and lung reactivation, and a core set of longer-term outcomes at 6 months). In exploratory analyses, we
will assess baseline factors as predictors for CMV reactivation, and characterize the relationship of CMV viral
load kinetics with VFDs and other clinical outcomes.
Our interdisciplinary team has unique experience in successfully coordinating multi-site multi-PI ICU-based
RCTs. We have established a network of 19 clinical sites in the US, all of which have robust infrastructure for
ICU clinical trials and proven ability to recruit patients into RCTs. If it is effective, this inexpensive and feasible
intervention has the potential to significantly improve care of patients with sepsis-associated respiratory failure,
substantially change clinical practice, and offer new insights into the sepsis-CMV reactivation relationship.
项目总结
项目成果
期刊论文数量(0)
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{{ truncateString('MICHAEL J BOECKH', 18)}}的其他基金
1/2 Ganciclovir to Prevent Reactivation of Cytomegalovirus in Patients with Acute Respiratory Failure and Sepsis
1/2 更昔洛韦预防急性呼吸衰竭和脓毒症患者巨细胞病毒再激活
- 批准号:
10656536 - 财政年份:2020
- 资助金额:
$ 212.01万 - 项目类别:
1/2 Ganciclovir to Prevent Reactivation of Cytomegalovirus in Patients with Acute Respiratory Failure and Sepsis
1/2 更昔洛韦预防急性呼吸衰竭和脓毒症患者巨细胞病毒再激活
- 批准号:
9976966 - 财政年份:2020
- 资助金额:
$ 212.01万 - 项目类别:
1/2 Ganciclovir to Prevent Reactivation of Cytomegalovirus in Patients with Acute Respiratory Failure and Sepsis
1/2 更昔洛韦预防急性呼吸衰竭和脓毒症患者巨细胞病毒再激活
- 批准号:
10274819 - 财政年份:2020
- 资助金额:
$ 212.01万 - 项目类别:
3rd Symposium on Infectious Diseases in the Immunocompromised Host
第三届免疫低下宿主传染病研讨会
- 批准号:
9762550 - 财政年份:2019
- 资助金额:
$ 212.01万 - 项目类别:
Training Program in Infectious Diseases in the Immunocompromised Host
免疫功能低下宿主传染病培训计划
- 批准号:
10450829 - 财政年份:2016
- 资助金额:
$ 212.01万 - 项目类别:
Training Program in Infectious Diseases in the Immunocompromised Host
免疫功能低下宿主传染病培训计划
- 批准号:
10744179 - 财政年份:2016
- 资助金额:
$ 212.01万 - 项目类别:
Training Program in Infectious Diseases in the Immunocompromised Host
免疫功能低下宿主传染病培训计划
- 批准号:
10270735 - 财政年份:2016
- 资助金额:
$ 212.01万 - 项目类别:
Training Program in Infectious Diseases in the Immunocompromised Host
免疫功能低下宿主传染病培训计划
- 批准号:
9925732 - 财政年份:2016
- 资助金额:
$ 212.01万 - 项目类别:
Training Program in Infectious Diseases in the Immunocompromised Host
免疫功能低下宿主传染病培训计划
- 批准号:
9428953 - 财政年份:2016
- 资助金额:
$ 212.01万 - 项目类别:
Training Program in Infectious Diseases in the Immunocompromised Host
免疫功能低下宿主传染病培训计划
- 批准号:
10666955 - 财政年份:2016
- 资助金额:
$ 212.01万 - 项目类别:
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