Maintenance Versus Reduction of Immunosuppression for Renal Transplant Patients Hospitalized With COVID-19 Disease
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Change in IL-6 concentration from baseline to day 7
研究概览
简要总结
This will be a randomized trial of maintenance versus reduction in immunosuppression in adult patients (age >18 years old) with functioning renal transplants admitted to hospital with confirmed COVID-19 disease.
详细描述
The optimal management of immunosuppression in renal transplant patients with COVID-19 disease is unclear. On one hand, many centers advocate reduction of immunosuppression in infected patients, with the rationale that such an approach will unleash the anti-viral T-cell response. However, on the other hand, some centers advocate there may be rationale to maintain baseline immunosuppression in order to mitigate against development of an uncontrolled over-activation of the immune response. The investigators propose to address this knowledge gap by performing a randomized clinical trial that will test formal comparisons of maintenance versus reduction in immunosuppression.
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
- Single (Outcomes Assessor)
盲法说明
This is a single-blind trial, in that only the assessor will be blinded to the treatment assignment.
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
- •Adults ≥18 years
- •COVID positive by RT-PCR or serology
- •≥ 6 months post-transplant
- •use of anti-metabolite (mycophenolate or azathioprine) and calcineurin inhibitor (cyclosporin or tacrolimus)
- •informed consent; first admission during study period
- •participation within 72 hours of hospitalization
排除标准
- •ICU care or need for invasive ventilation or use of pressors at screening/randomization
- •COVID-19 disease severity score more than 5 at screening/randomization
- •Known donor specific antibody
- •eGFR <20ml/min/1.73m2
- •hematocrit <24%
- •biopsy proven and treated rejection within last 3 months
- •institutionalized individuals (prisoners)
- •pregnancy
- •participation in another clinical study with an investigational medicinal product within 30 days or within 5 half-lives of such, whichever is longer, prior to randomization and during the study
- •any other conditions, which, in the opinion of the investigator would make the subject unsuitable.
研究组 & 干预措施
Maintenance of Immunosuppression
Maintenance of immunosuppression (defined as no change to pre-admission immunosuppression, or reduction in anti-metabolite by up to 50% (to a minimum of MMF 500 mg per day or azathioprine 50 mg per day)
干预措施: Maintenance or reduction of immunosuppression (Other)
Reduction of Immunosuppression
Reduction of immunosuppression (defined as anti-metabolite withdrawal plus reduction of tacrolimus or cyclosporin, to a minimum target trough concentration of 3 ng/mL for tacrolimus and 50 ng/mL for cyclosporin).
干预措施: Maintenance or reduction of immunosuppression (Other)
结局指标
主要结局
Change in IL-6 concentration from baseline to day 7
时间窗: baseline to day 7
次要结局
- Length of hospital stay(Through day 28)
- Change in IL-6 concentration from baseline to day 28(Baseline to day 28)
- Change in T cell response to SARS-CoV-2(Baseline to day 7 and day 28)
- Proportion of patients developing ANC < 500 cells per microliter(Through day 28)
- Proportion of patients developing biopsy-proven acute rejection(Through day 28)
- Adverse and serious adverse events(Through day 28)
- In-hospital and 28-day mortality(Through day 28)
- Change in COVID-19 disease severity score (range 1 to 8; higher worse)(Through day 28)
- Proportion of patients needing non-invasive ventilation or intubation(Through day 28)
- Proportion of patients developing lymphopenia < 400 cells per microliter(Through day 28)
- Change in titer of serum anti-SARS-CoV-2 antibodies(Baseline to day 7 and day 28)
研究者
Finnian McCausland
Associate Physician
Brigham and Women's Hospital