Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial
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|ClinicalTrials.gov Identifier: NCT04360876|
Recruitment Status : Not yet recruiting
First Posted : April 24, 2020
Last Update Posted : April 24, 2020
|Condition or disease||Intervention/treatment||Phase|
|COVID-19 ARDS||Drug: Dexamethasone injection Drug: Placebos||Phase 2|
Acute respiratory distress syndrome (ARDS) is a common, life-threatening pulmonary process which frequently requires mechanical ventilation and has a hospital mortality as high as 40%. No specific pharmacologic therapy has proven efficacy to treat ARDS. Corticosteroids have been investigated as a treatment for ARDS with conflicting results. Two sub phenotypes of ARDS have been described. One is hypo-inflammatory, associated with lower levels of circulating cytokines and therefore greater ventilator free days and a lower mortality. The second sub-phenotype is hyper-inflammatory with elevated cytokine levels, elevated acute phase reactants such as ferritin and c-reactive protein (CRP).
Many patients infected with the novel Coronavirus (SARS-CoV-2), the causative agent of CVOID-19, present with an exaggerated inflammatory response which leads to the hyper-inflammatory sub-phenotype of ARDS. These patients may derive great benefit from corticosteroids. Accordingly,this study will determine the safety and estimate efficacy of targeted corticosteroids in mechanically ventilated patients with the hyper-inflammatory sub phenotype of ARDS due to COVID-19
Hypothesis: Early administration of dexamethasone to patients with the hyper-inflammatory sub-phenotype of ARDS due to COVID-19 pneumonia is a safe intervention which increases ventilator free days
Approach: This is a single-center, phase 2a, pragmatic, randomized, double-blinded, placebo-controlled study accessing the safety and efficacy of dexamethasone for mechanically ventilated patients with ARDS due to COVID-19 infection. Primary outcome will be ventilator free days at day 28.
Understanding the safety and efficacy of corticosteroids in ARDS due to COVID-19 pneumonia could have dramatic implications for critically ill patients. Patients who present with an ARDS sub-type characterized by exaggerated inflammation may particularly benefit from this intervention. Corticosteroids may represent a simple and safe treatment for patients with the most severe form of COVID-19 infection and has the potential to save thousands of lives.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||90 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Single-center, Phase 2a, pragmatic, randomized, double-blinded, placebo-controlled|
|Masking:||Double (Participant, Care Provider)|
|Masking Description:||Participants confirmed to meet all eligibility criteria who have provided informed consent will be randomized 1:1 to dexamethasone versus placebo. A randomized group assignment will be provided to the investigator or research assistant. Randomization will be performed according to a central randomization scheme and will stratified by site in permuted blocks of varying size.|
|Official Title:||Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial|
|Estimated Study Start Date :||May 1, 2020|
|Estimated Primary Completion Date :||September 30, 2020|
|Estimated Study Completion Date :||December 31, 2020|
Patients assigned to the dexamethasone arm will receive an intravenous dose of 20 mg once daily from day 1 to day 5 which will be reduced to 10mg once daily from day 6 to day 10. Intravenous infusion bags divided into 10 doses will be provided at randomization by the investigational pharmacy. The time from randomization to time for first medication administration will be 4 hours or less. All infusions - dexamethasone and placebo - will be manufactured by the investigational pharmacy at the University of Colorado.
Drug: Dexamethasone injection
Dexamethasone intravenous 20mg daily for 5 days followed by 10mg daily for 5 days
Placebo Comparator: Placebo
Participants randomized to the control group will received placebo intravenously for 10 days, one dose per day. Intravenous infusion bags divided into 10 doses will be provided at randomization by the investigational pharmacy. The placebo infusion bags will be as similar as possible to the dexamethasone infusion bags to ensure blinding.
Placebo delivered intravenously on the same dosing schedule as dexamethasone
- Ventilator Free Days (VFD) at Day 28 [ Time Frame: 28 Days ]Total number of ventilator free days to day 28 of hospitalization. If a patient dies prior to day 28, they will be counted as zero ventilator free days. Follow up will be performed via phone or electronically to determine ventilator free status of those patients discharged prior to day 28.
- Clinical Status at day 14 as measured by World Health Organization (WHO) 7-point ordinal scale. [ Time Frame: 14 Days ]1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death.
- Clinical Status at day 28 as measured by WHO 7-point ordinal scale [ Time Frame: 28 Days ]
- In-Hospital Mortality at day 28 [ Time Frame: 28 Days ]
- In-Hospital Mortality at day 90 [ Time Frame: 90 Days ]
- Time to Mortality to day 28 [ Time Frame: 28 Days ]
- ICU-free days to day 28 [ Time Frame: 28 Days ]
- Hospital Length of Stay among survivors to day 90 [ Time Frame: 90 Days ]
- Severity of ARDS to day 10 [ Time Frame: 10 Days ]
- Days to resolution of fever [ Time Frame: 28 Days ]
- Change in C-Reactive Protein (CRP) level from baseline to day 10 [ Time Frame: 10 Days ]
- Vasopressor-free days to day 28 [ Time Frame: 28 Days ]
- Renal replacement-free days to day 28 [ Time Frame: 28 Days ]
- Duration of mechanical ventilation to day 28 [ Time Frame: 28 Days ]
- Oxygenation-free days to day 28 [ Time Frame: 28 Days ]
- Incidence of New Mechanical Ventilation to day 28 [ Time Frame: 28 Days ]
- Change in sequential organ failure assessment (SOFA) score from baseline to day 10 [ Time Frame: 10 Days ]
- In-hospital adverse events to day 28 [ Time Frame: 28 Days ]
- Discontinuation of study drug infusion [ Time Frame: 10 Days ]