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

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ClinicalTrials.gov Identifier: NCT04360876
Recruitment Status : Withdrawn (Funding not received)
First Posted : April 24, 2020
Last Update Posted : October 28, 2020
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE April 22, 2020
First Posted Date  ICMJE April 24, 2020
Last Update Posted Date October 28, 2020
Estimated Study Start Date  ICMJE September 1, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial
Official Title  ICMJE Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
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.
Primary Purpose: Treatment
Condition  ICMJE
  • COVID-19
  • ARDS
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Dexamethasone injection
  • 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.
    Intervention: Drug: Placebos
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: October 26, 2020)
0
Original Estimated Enrollment  ICMJE
 (submitted: April 22, 2020)
90
Estimated Study Completion Date  ICMJE January 30, 2021
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04360876
Other Study ID Numbers  ICMJE 20-0811
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: No Plan
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Colorado, Denver
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP