Efficacy and Safety of Corticosteroids in Oxygen-dependent Patients With COVID-19 Pneumonia in Grand Ouest Interregion France
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 主要终点
- Clinical improvement defined by the improvement of 2 points on a 7-category ordinal scale, at 14 days.
研究概览
简要总结
To date, there is no efficient therapeutics to prevent or treat COVID-19 related pulmonary failure. Corticosteroids (CS) could be a helpful therapeutic. Retrospective reports suggested survival improvement in patients with acute respiratory distress syndrome (ARDS). CT scan for COVID19 hospitalized patients showed sometimes unusual aspects of pneumonia, suggestive of an organizing phase of diffuse alveolar damage (DAD).
We hypothesize that, in the context of alveolar aggression induced by COVID-19, CT scan could help to individualize patients with a high probability of pulmonary organizing process who could benefit from CS treatment.
详细描述
"Severe acute respiratory syndrome" coronavirus 2 (SARS-Cov-2) is a new coronavirus that induces pneumonia called Corona Virus Disease- 19 (COVID-19), an infected 1.5 million people worldwide and caused the more than 85,000 patients died. COVID-19 usually comes in the form of viral pneumonia but with the peculiarities of a risk frequent worsening towards acute respiratory distress syndrome (ARDS) and a usual duration of oxygen dependence in fragile patients by their age or their comorbidities. To date, there is no therapy effective in preventing or treating COVID-19. Drug identification is a major concern and a public health emergency. Retrospective study (Wu 2020) highlighted improved survival in COVID-19 patients with acute ARDS and treated with corticosteroids (CS). So even in the absence of evidence of effectiveness, the SCs are used for COVID-19 oxygen-dependent patients or with an ARDS. However, their benefit / risk remains debated (Russel 2020). On histological samples of COVID-19, diffuse alveolar damage (DAD) has been especially observed (Hanley 2020). DAD is described histologically in an exudative phase, an organizational phase and a irreversible fibrotic phase (Hughes 2017). SC could have an effect beneficial by limiting the exudative / inflammatory phase but also that organization whose histological and CT aspects are sometimes indistinguishable from organized pneumonia, a form of pulmonary repair aberrant very corticosensitive (Travis 2013). Chest scans performed in the face of the persistence or worsening of oxygen dependence beyond the 7th day of COVID-19 symptoms, could help discern indirect complications (pulmonary embolism, exacerbation of COPD, bacterial superinfection, etc.) of an unfavorable course COVID-19 (by displaying an aspect suggesting DAD in particular during the organization phase). We hypothesize that, in the context of COVID-19, the SCs may be beneficial in patients with CT scans thoracic images suggestive of DAD either at the exudative phase or at the pulmonary organization phase.
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)
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
- •Adult patients ≥ 18 years old,
- •Hospitalized with a proven diagnosis of COVID-19 (SARS-CoV-2 positive in RTPCR), in medicine or in intensive care.
- •With a need for oxygen therapy ≥ 2 l / min to maintain a Sp02> 92% or a need for oxygen therapy to maintain a PaO2 / FiO2> 300 mmHg (for intubated patients).
- •With a chest scanner at least 7 days after the onset of symptoms, and whose centralized interpretation shows a CT scan aspect suggestive of intense and predominant DAD which can explain the patient's oxygen dependence.
- •Signature of a free, written and informed consent by the patient, or the person of trust
- •Affiliate or beneficiary of a social security scheme.
排除标准
- •Patients already treated by CS for a chronic disease.
- •Patients with a known contraindication to SC, such as hypersensitivity.
- •Patients at risk of dying within 48 hours.
- •Pregnant or breastfeeding women.
- •Patients under guardianship, curatorship, safeguard of justice.
- •Poor understanding of the French language.
研究组 & 干预措施
corticosteroid + Optimized Standard of Care
-
prednisone 0.7 mg/kg/day for 10 days, administered orally, once a day, or
-
hydrocortisone hemisuccinate 3.5 mg/kg/day by continuous infusion for 10 days, administered by IV route if the patient cannot take drugs by oral route,
-
standard of care
干预措施: Prednisone (Drug)
corticosteroid + Optimized Standard of Care
-
prednisone 0.7 mg/kg/day for 10 days, administered orally, once a day, or
-
hydrocortisone hemisuccinate 3.5 mg/kg/day by continuous infusion for 10 days, administered by IV route if the patient cannot take drugs by oral route,
-
standard of care
干预措施: Hydrocortisone (Drug)
结局指标
主要结局
Clinical improvement defined by the improvement of 2 points on a 7-category ordinal scale, at 14 days.
时间窗: 14 days
The 7-category ordinal scale is as follow: 1. Not hospitalized with resumption of usual activities 2. Not hospitalized, but unable to resume usual activities 3. Hospitalized, not requiring O2 4. Hospitalized, requiring O2 from 1 to 5 l/min 5. Hospitalized, requiring O2 \>6 l/min, nasal high-flow O2, non-invasive mechanical ventilation, or both 6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both 7. Death.
次要结局
- Proportion of patients discharged alive from hospital at day 14 and 28(14 and 28 days)
- The time until weaning from oxygen therapy(28 days)
- Proportion of patients free of oxygen at day 14 and 28(14 and 28 days)
- Time to discharge for patients alive(28 days)
- 14 and 28 day mortality rate(14 and 28 days)
- The proportion of patients with clinical degradation of at least 1 point on the ordinal scale to 7 categories on D14 and D28(14 and 28 days)
- Proportion of patients that were hospitalized to ICU or who died at day 14 and 28(14 and 28 days)