This trial will determine the safety and estimate efficacy of targeted corticosteroids in mechanically ventilated patients with the hyper-inflammatory sub phenotype of ARDS due to coronavirus disease 2019 (COVID-19) by implementing a Phase 2A clinical trial.
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.
Drug: Dexamethasone injection
Dexamethasone intravenous 20mg daily for 5 days followed by 10mg daily for 5 days
Drug: Placebos
Placebo delivered intravenously on the same dosing schedule as dexamethasone
Inclusion Criteria:
1. Male or Female Adult ≥ 18 years of age at time of enrollment
2. Laboratory confirmed SARS-CoV-2 infection determined by PCR within 14 days prior to
randomization and no alternative explanation for current clinical condition
3. Moderate or Severe ARDS (PaO2:FiO2 ratio ≤ 200mmHg) requiring mechanical ventilation
within 7 days prior to randomization
4. Hyper-inflammatory ARDS Sub-Phenotype defined as any one of the following:
1. C-Reactive Protein (CRP) > 100mg/dL
2. D-Dimer > 600ng/mL
3. IL-6 > 10pg/mL
5. Willing and/or able to comply with study-related procedures and assessments
6. Provide informed consent signed by study patient or legally acceptable representative
Exclusion Criteria:
1. Age < 18 years
2. In the opinion of the investigator, not expected to survive for more than 48 hours
from screening
3. Presence of any of the following abnormal laboratory values at screening
1. Absolute neutrophil count (ANC) < 2,000mm3
2. Alanine Transferase (ALT) or Aspartate Transferase (AST) > 5 times upper limit of
normal
4. Use of systemic corticosteroid therapy within 7 days of study enrollment
5. Known or suspected active bacterial, fungal or mycobacterial infections including
tuberculosis (TB)
6. Participation in a double-blind clinical research study evaluating an investigational
product or therapy within 3 months and less than 5 half-lives of investigational
product prior to the screening visit. Exception: The use of remdesivir,
hydroxychloroquine, or other treatments being used for COVID-19 infection in the
context of an open-label study or compassionate use protocol is permitted
7. Any physical examination findings, and/or history of any illness, concomitant
medication or recent live vaccines that, in the opinion of the study investigator,
might confound the results of the study or pose an additional risk to the patient by
their participation in the study
8. Prisoner
9. Pregnancy