Randomized Phase II Clinical Trial of Ruxolitinib Plus Simvastatin in the Prevention and Treatment of Respiratory Failure of COVID-19.Ruxo-Sim-20 Clinical Trial.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- Percentage of patients who develop severe respiratory failure.
研究概览
简要总结
COVID-19's mechanism to enter the cell is initiated by its interaction with its cellular receptor, the angiotensin-converting enzyme. As a result of this union, a clathrin-mediated endocytosis process begins. This route is one of the therapeutic targets for which available drugs are being investigated in order to treat COVID-19 infection. This is one of the mechanisms blocked by drugs like ruxolitinib and chloroquine.
Various drugs approved for clinical use that block the clathrin-mediated endocytosis pathway have been explored. It has been found that the best in vitro and in vivo results were obtained with statins, which also allowed generating a greater potent adaptive immune response.
Therefore, statins and specifically simvastatin make it possible to block the entry process used by COVID-19, block inflammation by various mechanisms and increase the adaptive immune response. All of these processes are desirable in patients infected with COVID-19.
Statins have been proposed to have beneficial effects in patients infected with MERS-COV, another coronavirus similar to COVID-19, but there have been no randomized studies supporting the use of statins in patients with COVID-19 infection.
In this project we propose the combined use of one of these drugs, ruxolitinib with simvastatin, looking for a synergistic effect in the inhibition of viral entry and in the anti-inflammatory effect.
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
- •Patients who have given their written informed consent. If it is considered that obtaining written consent could constitute a factor for the transmission of the disease (given the high contagiousness of the SARS-Cov-2 virus), it will be permitted to obtain duly justified verbal consent in the patient's medical history.
- •Clinical diagnosis or confirmed by analytical tests (PCR of viral RNA or detection of antiSARS-Cov-2 antibodies) that requires care in hospital and that are grade 3 or 4 of the WHO 7-point ordinal scale of severity categorization for COVID.
- •Platelets> 50,000 / uL, neutrophils> 500 / ul
- •Kidney or liver failure is not a contraindication, dose adjustment will be made according to the SmPC
- •Women of childbearing potential who are sexually active, not undergoing a hysterectomy or double adnexectomy, should follow the following indications for contraception:
- •Negative serum or urine pregnancy test in the 72 hours prior to the start of treatment.
- •Use of a medically accepted contraceptive method during: 2 months prior to the start of study treatment, during the study and up to 3 months after the last dose of treatment.
排除标准
- •Documented concomitant severe bacterial or fungal infection
- •Infection with HIV, HCV, HBV
- •Age <18 years
- •Thrombocytopenia <50,000 / uL, Neutropenia <500 / uL
- •Women of childbearing age who do not use an effective contraceptive method.
- •Pregnant or lactating women.
- •Patients who do not want or cannot comply with the protocol.
- •Patients with impaired gastrointestinal function or gastric disease that significantly impairs the absorption of ruxolitinib or simvastatin, such as: severe ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, extensive resection (> 1m) of the small intestine or inability to swallow oral medication. Previous partial or total gastrectomy is not an exclusion criterion
研究组 & 干预措施
Ruxolitinib plus simvastatin
Ruxolitinib 5 mg orally every 12 hours for 7 days, which will be increased to 10 mg every 12 hours for a total of 14 days.
Simvastatin 40 mg orally every 24 hours for 14 days.
干预措施: Ruxolitinib plus simvastatin (Drug)
Standard of Care
Patients will receive treatment according to usual clinical practice in the participant site.
干预措施: Standard of Care (Other)
结局指标
主要结局
Percentage of patients who develop severe respiratory failure.
时间窗: 7 days
Patients achieving a grade 5 or higher of the WHO 7-point ordinal scale of severity categorization for COVID at day 7 from randomization.
次要结局
- Length of ICU stay.(28 days)
- Survival rate at 12 months(12 months)
- Percentage of patients with each AE by grade(28 days)
- Length of hospital stay(28 days)
- Percentage of patients who develop severe respiratory failure.(14 days)
- Survival rate at 6 months(6 months)
- Survival rate at 28 days(28 days)
- Percentage of patients who discontinued due to AEs(28 days)