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History of Changes for Study: NCT04360876
Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial
Latest version (submitted October 26, 2020) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 April 22, 2020 None (earliest Version on record)
2 July 13, 2020 Study Status
3 October 26, 2020 Recruitment Status, Study Status, Study Design and Oversight
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Study NCT04360876
Submitted Date:  April 22, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: 20-0811
Brief Title: 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
Secondary IDs:
Open or close this module Study Status
Record Verification: April 2020
Overall Status: Not yet recruiting
Study Start: May 1, 2020
Primary Completion: September 30, 2020 [Anticipated]
Study Completion: December 31, 2020 [Anticipated]
First Submitted: April 22, 2020
First Submitted that
Met QC Criteria:
April 22, 2020
First Posted: April 24, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
April 22, 2020
Last Update Posted: April 24, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: University of Colorado, Denver
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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.

Open or close this module Conditions
Conditions: COVID-19
ARDS
Keywords: Corticosteroids
Dexamethasone
COVID-19 Pneumonia
ARDS
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Single-center, Phase 2a, pragmatic, randomized, double-blinded, placebo-controlled
Number of Arms: 2
Masking: Double (Participant, Care Provider)
Allocation: Randomized
Enrollment: 90 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Dexamethasone
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.
Drug: Placebos
Placebo delivered intravenously on the same dosing schedule as dexamethasone
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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.
Secondary Outcome Measures:
1. 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.
2. Clinical Status at day 28 as measured by WHO 7-point ordinal scale
[ Time Frame: 28 Days ]

3. In-Hospital Mortality at day 28
[ Time Frame: 28 Days ]

4. In-Hospital Mortality at day 90
[ Time Frame: 90 Days ]

5. Time to Mortality to day 28
[ Time Frame: 28 Days ]

6. ICU-free days to day 28
[ Time Frame: 28 Days ]

7. Hospital Length of Stay among survivors to day 90
[ Time Frame: 90 Days ]

8. Severity of ARDS to day 10
[ Time Frame: 10 Days ]

9. Days to resolution of fever
[ Time Frame: 28 Days ]

10. Change in C-Reactive Protein (CRP) level from baseline to day 10
[ Time Frame: 10 Days ]

11. Vasopressor-free days to day 28
[ Time Frame: 28 Days ]

12. Renal replacement-free days to day 28
[ Time Frame: 28 Days ]

13. Duration of mechanical ventilation to day 28
[ Time Frame: 28 Days ]

14. Oxygenation-free days to day 28
[ Time Frame: 28 Days ]

15. Incidence of New Mechanical Ventilation to day 28
[ Time Frame: 28 Days ]

16. Change in sequential organ failure assessment (SOFA) score from baseline to day 10
[ Time Frame: 10 Days ]

17. In-hospital adverse events to day 28
[ Time Frame: 28 Days ]

18. Discontinuation of study drug infusion
[ Time Frame: 10 Days ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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
Open or close this module Contacts/Locations
Locations:
Open or close this module IPDSharing
Plan to Share IPD: No
No Plan
Open or close this module References
Citations:
Links:
Available IPD/Information:

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