Open Randomized Single Centre Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With Severe Lung Injury Secondary to COVID-19
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Time to reach clinical stability
研究概览
简要总结
The primary objective of the study is to evaluate the days until reaching clinical stability after starting randomization in hospitalized patients with elevated inflammatory parameters and severe COVID-19 lung injury.
详细描述
Unfortunately, the treatment of COVID-19 disease is still based on life support therapies. Nowadays, there is no scientific evidence from clinical trials regarding the efficacy or safety of different drugs to treat COVID-19 patients, despite some of them evolving to fatal severe lung injury due to important inflammatory process secondary to pro-inflammatory cytokines. Interestingly, Tacrolimus has been shown to inhibit both pro-inflammatory cytokines and, also, human coronavirus SARS-Cov replication, but it has not specifically been tested in COVID-19 patients.
Our working hypothesis is that severe SARS-CoV-2 (COVID-19) pneumonia is secondary to a deleterious inflammatory process; so, the use of Methylprednisolone pulses and Tacrolimus in hospitalized severe COVID-19 lung injury patients might have a positive clinical effect.
Given the COVID-19 current health emergency, this study could provide useful evidence to treat some COVID-19 patients with Methylprednisolona and Tacrolimus, which might represent a new therapeutic option for them. Tacrolimus is a drug with more than 20 years of experience, and therefore, its side effects are well known and usually reversible. In addition, since tacrolimus is a low-cost and easy to produce at large-scale drug, it could be used to treat a large number of patients. The administration of this drugs could not only decrease mortality secondary to lung involvement by COVID-19, but also decrease the excessive burden of care that intensive care units are bearing.
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
The statistician who will finally carry out the analyses will be blind to the treatment received by the patients
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
- •COVID-19 infection confirmed by PCR
- •New onset radiological infiltrates
- •Respiratory failure (PaO2 / FiO2 <300 or satO2 / FiO2 <220)
- •PCR>100 mg/L and/or D-Dimer>1000 µg/L and/or Ferritin>1000 ug/L
- •Informed consent.
排除标准
- •Life expectancy ≤ 24h
- •Glomerular filtration ≤ 30 ml / min / 1.73 m2
- •Leukopenia ≤ 4000 cells / µL
- •Concomitant potentially serious infections.
- •Contraindication for the use of tacrolimus according to the specifications of the product
- •Known adverse reactions to treatment
- •Have participated in a clinical trial in the last 3 months
研究组 & 干预措施
Intervention
Methylprednisolone pulses 120mg/day for 3 consecutive days (if they were not previously administered) with Tacrolimus at the necessary dose to achieve plasma levels of 8-10 ng/ml.
In addition, these patients can receive all the treatments considered necessary for their clinical management.
干预措施: Tacrolimus (Drug)
Intervention
Methylprednisolone pulses 120mg/day for 3 consecutive days (if they were not previously administered) with Tacrolimus at the necessary dose to achieve plasma levels of 8-10 ng/ml.
In addition, these patients can receive all the treatments considered necessary for their clinical management.
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
Time to reach clinical stability
时间窗: 28 days
Assess the days until clinical stability is achieved after initiating randomization in hospitalized patients with elevated inflammatory parameters and severe COVID-19 lung injury. Clinical stability is defined if all the following criteria are met for 48 consecutive hours: Body temperature ≤ 37.0ºC; PaO2 / FiO2\> 400 and / or SatO2 / FiO2\> 300; Respiratory rate ≤ 24 rpm
次要结局
- Need for ventilatory support devices(56 days)
- Study the impact of immunosuppressive treatment on viral load using quantitative PCR(56 days)
- Time to normalization of D-dimer (<250 ug / L)(56 days)
- Time until PCR normalization (<5mg / L).(56 days)
- Time until normalization of ferritin (<400ug / L)(56 days)
- Time to reach an afebrile state for 48 hours.(56 days)
- Time to reach PaO2 / FiO2> 400 and / or SatO2 / FiO2> 300(56 days)
- Time to reach FR ≤ 24 rpm for 48 hours(56 days)
- Time until hospital discharge(56 days)
- Duration that it is necessary to maintain ventilatory support.(56 days)
- COVID-19 mortality(56 days)
- all-cause mortality(56 days)
- Analyze the expanded cytokine profile before the start of treatment and their evolution every 7 days after admission(56 days)
- Describe the side effects and their severity attributed to tacrolimus and / or methylprednisolone.(56 days)
研究者
Xavier Solanich
Xavier Solanich, MD
Hospital Universitari de Bellvitge