Assessment of doubling dose of dexamethasone in progressively worsening severe COVID-19 pneumonia not responding to standard dose - an open-label pragmatic randomized controlled trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Supplemental oxygen-free days at day 28 from hospitalization
研究概览
简要总结
This is a single centre, open label, parallel-arm, randomized trial to assess whether dexamethasone 6mg alone versus escalation of dexamethasone to 12mg in patients with progressive severe COVID 19 illness would be effective in improving the outcomes of patients with severe COVID 19 infection. This study would be conducted in the Trauma center (TC), AIIMS, which is a dedicated COVID center. The diagnosed cases of COVID-19 pneumonia with hypoxemia who would fulfil the criteria for severe COVID-19 as per the CDC definition (SpO2 <94% on room air, a ratio of arterial partial pressure of oxygen to FiO2 (PaO2/FiO2) <300 mm Hg or respiratory rate(RR) >30 breaths/min) would be included. This definition encompasses both moderate (SpO2 <94%) and severe (SpO2 <90%) COVID-19 pneumonia as per our institute protocol. All eligible patients would be recruited and initiated on standard care **(**remdesivir 200mg i.v. loading dose, followed by 100 mg i.v. once daily for 4 days, and anticoagulation-LMWH such as enoxaparin 0.1 mg/kg upto 40 mg according to the institute COVID 19 treatment protocol). Patients whose respiratory parameters worsen or remain plateau on standard of care beyond 24 hours upto 5 days of admission would be randomized to one of two arms (A) and (B).
- Arm A: Dose of steroids increased (12 mg i.v. once daily, i.v. or oral)
- Arm B: Dose of steroids unchanged (6 mg i.v. once daily or oral
The duration of the steroid in either arm would be for a total period of 10 days or till the patient’s discharge from the hospital, whichever is earlier. The objective of the study is to evaluate the outcome of doubling the dose of steroid in patients with severe covid 19 pneumonia, those who worsen or remain plateau within 5 days of hospitalization compared to standard of care.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Patients aged at least 18 years, hospitalised, confirmed SARS-CoV-2 infection by nucleic acid based testing (RT-PCR, CB-NAAT, or TrueNAT) or antigen testing, Severe COVID-19 pneumonia (SpO2 <94%; PaO2/FiO2 <300 mm Hg or respiratory rate(RR) >30 breaths/min) with lack of response to Dexamethasone 6 mg after 48 hours [defined as similar or worsening oxygen requirement (margin of error is 5% Fio2 for high flow nasal cannula, 2 L/min for NRBM, and 1 L/min for low flow oxygen devices)].
排除标准
- •Patient already on corticosteroid therapy for an unrelated indication; Patient with impending death or respiratory failure necessitating ICU care within 24 hours including inability to maintain SpO2 ≥90% despite HFNC with flow 60 L/min and FiO2 1.0 or ,if available, NIV with PEEP of upto 8 cm H2O and FiO2 1.0; Patients who have received ≥2 day of steroids outside hospital care or within the hospital outside of wards that are involved in the study.
- •These doses must be no greater than 12 mg dexamethasone or 64 mg methylprednisolone cumulatively; Patients with a known contraindication to corticosteroids including untreated bacterial sepsis, diabetic keto-acidosis, and invasive fungal infections such as mucormycosis; medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial; Pregnancy; Recruitment in another therapeutic trial; Use of immunosuppressive drugs, cytotoxic chemotherapy in the past 21 days; Neutropenia due to hematological or solid malignancies with bone marrow invasion; Refusal of consent.
结局指标
主要结局
Supplemental oxygen-free days at day 28 from hospitalization
时间窗: Day 28 from hospitalisation, during hospital course
Proportion of patients requiring non-invasive ventilation by NIV mask or invasive mechanical ventilation
时间窗: Day 28 from hospitalisation, during hospital course
次要结局
- Number of days to requirement for NIV or invasive mechanical ventilation(During Hospital course)
- In-hospital mortality(At death/discharge)
- All cause mortality at day 28 from hospitalization(Day 28 from hospitalisation)
- Hospital length of stay(At death/discharge)
- Proportion of patients requiring antimicrobial therapy for suspected hospital acquired infection (bacterial or fungal)(During hospital course)
- Clinical status after 5 as well as 10 days after hospitalization with 9-point WHO ordinal scale(Day 5 and 10 after hospitalisation)
- Severity of steroid induced hyperglycemia including average daily glucose measurements and average daily insulin administered per kilogram body weight from day 1-5 after randomization(Day 1-5 after randomisation during hospital course)