Clinical trial NCT04360876: Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial
Official title: Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: COVID-19
ARDS
Keywords: Corticosteroids
Dexamethasone
COVID-19 Pneumonia
ARDS
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2020-04-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-center, Phase 2a, pragmatic, randomized, double-blinded, placebo-controlled
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Ventilator Free Days (VFD) at Day 28
timeFrame: 28 Days
Secondary outcomes:
measure: Clinical Status at day 14 as measured by World Health Organization (WHO) 7-point ordinal scale.
timeFrame: 14 Days
measure: Clinical Status at day 28 as measured by WHO 7-point ordinal scale
timeFrame: 28 Days
measure: In-Hospital Mortality at day 28
timeFrame: 28 Days
measure: In-Hospital Mortality at day 90
timeFrame: 90 Days
measure: Time to Mortality to day 28
timeFrame: 28 Days
measure: ICU-free days to day 28
timeFrame: 28 Days
measure: Hospital Length of Stay among survivors to day 90
timeFrame: 90 Days
measure: Severity of ARDS to day 10
timeFrame: 10 Days
measure: Days to resolution of fever
timeFrame: 28 Days
measure: Change in C-Reactive Protein (CRP) level from baseline to day 10
timeFrame: 10 Days
measure: Vasopressor-free days to day 28
timeFrame: 28 Days
measure: Renal replacement-free days to day 28
timeFrame: 28 Days
measure: Duration of mechanical ventilation to day 28
timeFrame: 28 Days
measure: Oxygenation-free days to day 28
timeFrame: 28 Days
measure: Incidence of New Mechanical Ventilation to day 28
timeFrame: 28 Days
measure: Change in sequential organ failure assessment (SOFA) score from baseline to day 10
timeFrame: 10 Days
measure: In-hospital adverse events to day 28
timeFrame: 28 Days
measure: Discontinuation of study drug infusion
timeFrame: 10 Days
Other outcomes:
Locations:
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