Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial

COVID-19 Clinical Trial

Official title:

Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04360876
• Other study ID #: 20-0811
• Status: Withdrawn
• Phase: Phase 2
• Start date: September 1, 2020
• Est. completion date: January 30, 2021

Study information

• Verified date: October 2020
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 30, 2021
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• ARDS
• COVID-19
• Pneumonia

Intervention

Drug:
• Dexamethasone injection
Dexamethasone intravenous 20mg daily for 5 days followed by 10mg daily for 5 days
• Placebos
Placebo delivered intravenously on the same dosing schedule as dexamethasone

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Outcome

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