Randomized Controlled Trial of Methylprednisolone Versus Dexamethasone in COVID-19 Pneumonia (MEDEAS Trial)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 690
- 试验地点
- 1
- 主要终点
- Survival
研究概览
简要总结
Low-dose glucocorticoid treatment is the only intervention shown to significantly reduce mortality in cases of COVID-19 pneumonia requiring oxygen supplementation or ventilatory support. In particular, a large UK randomized controlled trial (RECOVERY trial) demonstrated the efficacy of dexamethasone at a dosage of 6mg/day for 10 days in reducing mortality compared to usual therapy, with a greater impact on patients requiring mechanical ventilation (36% reduction) or oxygen therapy (18% reduction) than on those who did not need respiratory support (doi: 10.1056/NEJMoa2021436). However, there is still paucity of information guiding glucocorticoid administration in severe pneumonia/ARDS and no evidence of the superiority of a steroid drug -nor of a therapeutic scheme- compared to the others, which led to a great heterogeneity of treatment protocols and misinterpretation of available findings. In a recent longitudinal observational study conducted in Italian respiratory high-dependency units, a protocol with prolonged low-dose methylprednisolone demonstrated a 71% reduction in mortality and the achievement of other secondary endpoints such as an increase in ventilation-free days by study day 28 in a subgroup of patients with severe pneumonia and high levels of systemic inflammation (doi: 10.1093/ofid/ofaa421). The treatment was well tolerated and did not affect viral shedding from the airways. In light of these data, the present study aims to compare the efficacy of a methylprednisolone protocol and that of a dexamethasone protocol based on previous evidence in increasing survival by day 28, as well as in reducing the need and duration for mechanical ventilation, among hospitalized patients requiring noninvasive respiratory support (oxygen supplementation and/or noninvasive ventilation).
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
- •Able to understand and sign the informed consent
- •SARS-CoV-2 positive on at least one upper respiratory swab or bronchoalveolar lavage
- •PaO2 <= 60 mmHg or SpO2 <= 90% or on oxygen therapy (any), CPAP or NPPV at randomization
- •Age >= 18 years old at randomization
排除标准
- •On invasive mechanical ventilation (either intubated or tracheostomized)
- •Heart failure as the main cause of acute respiratory failure
- •On long-term oxygen or home mechanical ventilation
- •Decompensated liver cirrhosis
- •Immunosuppression (i.e., cancer on treatment, post-organ transplantation, HIV-positive, on immunosuppressant therapy)
- •On chronic steroid therapy or other immunomodulant therapy (e.g., azathioprine, methotrexate, mycophenolate, convalescent/hyperimmune plasma)
- •Chronic renal failure with dialysis dependence
- •Progressive neuro-muscular disorders
- •Cognitively impaired, dementia or decompensated psychiatric disorder
- •Quadriplegia/Hemiplegia or quadriparesis/hemiparesis
- •Do-not-resuscitate order
- •Participating in other clinical trial including experimental compound with proved or expected activity against SARS-CoV-2 infection
- •Any other condition that in the opinion of the investigator may significantly impact with patient's capability to comply with protocol intervention
- •Refuse to participate in the study or absence of signed informed consent form.
研究组 & 干预措施
Methylprednisolone
A. On day 1, loading dose of methylprednisolone (MP) 80 mg IV in 30 minutes, promptly followed by continuous infusion of MP 80 mg/day in 240 mL of normal saline at 10 mL/h.
B. From day 2 to day 8: infusion of MP 80 mg/day in 240 mL of normal saline at 10 mL/h.
C. From day 9 and beyond:
- If not intubated patient and PaO2/FiO2 > 200, taper to MP 20 mg IV in 30 minutes three times a day for 3 days, then MP 20 mg IV twice daily for 3 days, then MP 20 mg IV once daily for 2 days, then switch to MP 16 mg/day PO for 2 days, then MP 8mg/day PO for 2 days, then MP 4mg/day PO for 2 days;
- If intubated patient or PaO2/FiO2 <= 200 with at least 5 cmH2O CPAP, continue infusion of MP 80 mg/day in 240 mL of normal saline at 10 mL/h until PaO2/FiO2 > 200 then taper as in a)
干预措施: Methylprednisolone (Drug)
Dexamethasone
A. Dexamethasone (DM) 6 mg IV in 30 minutes or PO from day 1 to day 10 or until hospital discharge (if sooner).
B. After day 10 study treatment is interrupted.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Survival
时间窗: 28 days
Survival proportion at 28 days in both arms
次要结局
- Disease progression(Day 3, 7 and 14)
- Reduction in the need for mechanical ventilation(28 days)
- Length of hospitalization(From date of randomization until the date of hospital discharge, assessed up to 60 days)
- Need for tracheostomy(Day 28)
- Reduction in systemic inflammation markers(Day 3, 7 and 14)
- Amelioration of oxygenation(Day 3, 7 and 14)
研究者
Confalonieri Marco, MD
Professor
University of Trieste