HORUS-Cytomegalovirus Open Proof-of-concept Exploratory Trial (HORUS-COPE): An International Proof-of-concept Clinical Trial on Modulation of Immunosuppressive Regimen in Solid-organ Transplant Recipients With Cytomegalovirus Infection.
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 100
- 试验地点
- 4
- 主要终点
- Viral load decay
研究概览
简要总结
Cytomegalovirus (CMV) remains a significant cause of morbidity and mortality following organ transplantation.
Cell-mediated immunity plays a crucial role in controlling CMV replication after transplantation. Immune monitoring involves the use of immune biomarkers to dynamically estimate the risk of CMV replication. This approach allows for the individualization of preventive and therapeutic strategies, improving patient outcomes.
The HORUS-COPE trial is designed to assess the effect of immune modulation on CMV replication kinetics and to explore the performance of a selected immune signature during antiviral therapy for CMV infection to stratify patients based on their risk of not responding to immune modulation.
详细描述
Cytomegalovirus (CMV) remains a significant cause of morbidity and mortality following organ transplantation.
Cell-mediated immunity plays a crucial role in controlling CMV replication after transplantation. Immune monitoring involves the use of immune biomarkers-primarily those assessing cell-mediated immunity-to dynamically estimate the risk of CMV replication. This approach allows for the individualization of preventive and therapeutic strategies, improving patient outcomes.
The HORUS consortium is a comprehensive European research initiative aimed at providing an in-depth assessment of immune signatures associated with CMV immune control in SOT recipients. One of the ultimate goals of the HORUS project is to leverage these immune signatures to design and implement a clinical trial evaluating their feasibility and impact in routine clinical practice.
As part of this initiative, we introduce the HORUS-COPE trial, designed to assess the effect of immune modulation on CMV replication kinetics and to explore the performance of a selected immune signature during antiviral therapy for CMV infection to stratify patients based on their risk of not responding to immune modulation.
Specifically, immune modulation consists of either:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinically stable adult patients (aged 18 years or older) who have received a solid organ transplant (e.g., kidney, liver, heart, lung, pancreas) and developed clinically significant CMV infection as determined by positive CMV PCR.
- •On maintenance therapy of tacrolimus, MPA, +/- steroids.
- •Informed consent signed.
排除标准
- •Active acute graft rejection or significant graft dysfunction requiring modification of the current immunosuppressive regimen, in the opinion of the investigator.
- •Receipt of more than 72 hours of antiviral therapy for CMV infection prior to enrolment, before randomization, including valganciclovir and/or IV ganciclovir therapy
- •Known intolerance or hypersensitivity to mTOR inhibitors or to any component of the everolimus formulation.
- •Any medical condition that constitutes a contraindication to everolimus use, as judged by the investigator.
- •Additional exclusion criteria for French sites:
- •Patient not affiliated to the French social security system
- •Patient under legal protection (guardianship, curatorship).
研究组 & 干预措施
50% reduction in the dose of MPA for a duration of minimum 21 days
with standard antiviral therapy
干预措施: 50% reduction in the dose of MPA (Drug)
switch of MPA to everolimus with adapted dose of tacrolimus, for a duration of at least 56 days
with standard antiviral therapy
干预措施: Switch from MPA to a mammalian target of rapamycin inhibitor (mTORi), together with an adapted dose of tacrolimus (Drug)
Standard antiviral therapy without modulation of immunosuppression
干预措施: standard antiviral therapy along with maintenance of their initial immunosuppressive therapy. (Drug)
结局指标
主要结局
Viral load decay
时间窗: 3 weeks
Differences in log CMV viral load in plasma between baseline and 3 weeks
次要结局
- Change in CMV-specific immune signature score(from enrollment to 3 and 8 weeks)
- Viral load decay according to immune signature(3 and 8 weeks)
研究者
Oriol Manuel
Associated Professor
University of Lausanne Hospitals