Early Treatment Strategy With High-dose Dexamethasone Versus Standard Dose in Patients With SARS-CoV-2 Pneumonia (COVID-19). PREDEXACOV Study
试验速览
- 阶段
- 3 期
- 入组人数
- 200
- 主要终点
- Evaluate if there is a decrease in the proportion of patients who develop respiratory distress
研究概览
简要总结
Early identification and treatment of this inflammatory cascade using existing therapeutic strategies with proven safety profiles could change the course and prognosis of COVID-19 infection, reducing mortality rates. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death
详细描述
The use of corticosteroids in COVID 19 in hospitalized patients with moderate symptoms has not been adequately studied in randomized clinical trials, the studies and clinical trials having focused on critical or severe patients. The few studies available to date have yielded evidence of low certainty.
Our trial postulates that early intervention and treatment with high-dose corticosteroids (20 mg dexamethasone for 3 days) in patients admitted with pneumonia with respiratory failure and moderate elevation of acute phase reactants and proinflammatory cytokines, or with risk factors that condition worse prognosis on admission, and who have not yet developed data on respiratory distress, the development of the cytokine storm could be avoided or minimized, reducing lung tissue damage and progression to severe respiratory failure and, therefore, reducing the need for invasive and noninvasive respiratory therapies, reducing hospital stay and, possibly, reducing associated mortality.
Dexamethasone is a potent synthetic glucocorticoid with actions resembling those of steroid hormones. It acts as an anti-inflammatory and immunosuppressant. It is a widely known glucocorticoid, studied and used in the treatment of autoimmune diseases, in oncology patients under chemotherapy to counteract certain side effects of their antitumor treatment, to augment the antiemetic effects of 5-HT3 receptor antagonists, in patients with brain neoplasms (primary or metastatic) to reduce edema, in spinal cord compressions, in certain hematological malignancies, in the treatment of arthropathies, to counteract allergic shock and septic shock, among many other indications for use. It is also used for the diagnosis of diseases related to hypothalamic-pituitary-adrenal axis dysfunction.
Recently, following the DEXA-COVID, CoDEX and RECOVERY clinical trials, dexamethasone has been widely used in patients with severe or critical SARS-CoV-2 pneumonia.
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
盲法说明
Patients who meet all inclusion criteria and none of the exclusion criteria will be randomized to receive a daily dose of dexamethasone 20 mg intravenous for 3 days, followed by a daily dose of oral or intravenous dexamethasone 6 mg for 7 more days versus the center's standard treatment which includes the use of oral or intravenous dexamethasone 6 mg for 10 days with escalation to a daily dose of oral or intravenous dexamethasone 20 mg for 3 days if clinical criteria of respiratory distress develop despite treatment with dexamethasone 6 mg daily.
Randomization will be performed in a centralized manner. Randomization will be done directly in the database itself by including the patient in the CRD-e (Redcap). When the investigator registers a patient in the CRD-e, the system will directly assign him/her to which group he/she has been randomized.
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 admitted with SARS-CoV-2 (COVID19) pneumonia confirmed by antigenic test or PCR Age ≥ 18 yrs.
- •pcr ≥ 66 mg/L and ≤150 mg/L at inclusion or Pandemic score at admission > 200 with pcr 9.7-149 mg/L at inclusion.
- •WHO scale level 4, with need for oxygen therapy in NG ≥ 1 lpm to maintain saturation ≥ 94%.
- •Onset of symptoms ≤ 10 days before the date of inclusion.
- •After having received verbal and written information about the study, the patient must submit the signed and dated Informed Consent before performing any activity related to the study.
排除标准
- •Patients with respiratory distress criteria at the time of randomization, understood as need for OCNAF/VMNI/VMI (levels 5 and 6 of the WHO scale) or O2 saturation ≤ 92% and/or FR ≥ 30 despite oxygen in NG at 4 liters.
- •Patients with allergy or contraindication to the use of systemic corticosteroids.
- •Patients with severe asthma or chronic pulmonary pathology with home oxygen requirements and active treatment with corticosteroids.
- •Patients on chronic corticosteroid treatment.
- •Use of corticosteroids daily in the 15 days prior to hospital admission.
- •Indication of corticosteroid use due to other clinical conditions of the patient (e.g., septic shock).
- •Pregnant or actively breastfeeding women
- •Patients with suspected or confirmed bacterial, fungal, or viral infection other than SARS-CoV-2 itself at the time of randomization
- •Patients with confirmed past or latent tuberculosis infection prior to inclusion.
- •Patients with known HIV infection with CD4 below 500 cells/mm3 or on active treatment with protease inhibitors or boosters such as cobicistat or ritonavir.
- •Patients with active oncologic processes in the last year or in active treatment with chemotherapy.
- •Patients with life expectancy < 3 months at inclusion due to clinical conditions other than SARS-CoV-2 pneumonia.
- •Patients with expected death in the following 48-72 hours.
- •Patients included in another clinical trial.
研究组 & 干预措施
Experimental arm
A daily dose of dexamethasone 20 mg intravenous for 3 days, followed by a daily dose of dexamethasone 6 mg intravenous or oral for 7 days.
干预措施: Dexamethasone (Drug)
Standard treatment regimen
Dexamethasone 6 mg orally or intravenously for 10 days (with the possibility of escalation to doses of 20 mg daily of oral or intravenous dexamethasone for 3 days if clinical criteria of respiratory distress develop despite treatment with doses of dexamethasone 6 mg daily).
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Evaluate if there is a decrease in the proportion of patients who develop respiratory distress
时间窗: Week 12
* To evaluate whether there is a decrease in the proportion of patients who develop respiratory distress with the need for NIV/MIV/OCNAF (measured group and individually by respiratory therapies). * To evaluate the impact of this strategy on the number of days of hospitalization.
次要结局
- Evaluate if there is a decrease in the number of therapy days(W12)