COVID-19Phase 2NCT04360876
Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial
A Phase 2 study testing Dexamethasone injection in people with COVID-19 and ARDS, run by University of Colorado, Denver.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Dexamethasone injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2020to 30 Jan 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or Female Adult ≥ 18 years of age at time of enrollment
- Laboratory confirmed SARS-CoV-2 infection determined by PCR within 14 days prior to randomization and no alternative explanation for current clinical condition
- Moderate or Severe ARDS (PaO2:FiO2 ratio ≤ 200mmHg) requiring mechanical ventilation within 7 days prior to randomization
- Hyper-inflammatory ARDS Sub-Phenotype defined as any one of the following:
- C-Reactive Protein (CRP) > 100mg/dL
- D-Dimer > 600ng/mL
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- IL-6 > 10pg/mL
- Willing and/or able to comply with study-related procedures and assessments
- Provide informed consent signed by study patient or legally acceptable representative
Who cannot join
- Age < 18 years
- In the opinion of the investigator, not expected to survive for more than 48 hours from screening
- Presence of any of the following abnormal laboratory values at screening
- Absolute neutrophil count (ANC) < 2,000mm3
- Alanine Transferase (ALT) or Aspartate Transferase (AST) > 5 times upper limit of normal
- Use of systemic corticosteroid therapy within 7 days of study enrollment
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- Known or suspected active bacterial, fungal or mycobacterial infections including tuberculosis (TB)
- 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
- 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
- Prisoner
- Pregnancy
About this study
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.
Read the 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.
- Being tested
- Dexamethasone injection, Placebos
- Keywords
- Corticosteroids, Dexamethasone, COVID-19 Pneumonia, ARDS
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dexamethasone injectionDrug
Dexamethasone intravenous 20mg daily for 5 days followed by 10mg daily for 5 days
PlacebosDrug
Placebo delivered intravenously on the same dosing schedule as dexamethasone
| Study group | Role | What they receive |
|---|---|---|
| Dexamethasone | Experimental | 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. Receives: Drug: Dexamethasone injection |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 Days
Secondary outcomes (18)
Clinical Status at day 14 as measured by World Health Organization (WHO) 7-point ordinal scale.
- 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.
Measured: 14 Days
Clinical Status at day 28 as measured by WHO 7-point ordinal scale
Measured: 28 Days
In-Hospital Mortality at day 28
Measured: 28 Days
In-Hospital Mortality at day 90
Measured: 90 Days
Time to Mortality to day 28
Measured: 28 Days
ICU-free days to day 28
Measured: 28 Days
Hospital Length of Stay among survivors to day 90
Measured: 90 Days
Severity of ARDS to day 10
Measured: 10 Days
Days to resolution of fever
Measured: 28 Days
Change in C-Reactive Protein (CRP) level from baseline to day 10
Measured: 10 Days
Vasopressor-free days to day 28
Measured: 28 Days
Renal replacement-free days to day 28
Measured: 28 Days
Duration of mechanical ventilation to day 28
Measured: 28 Days
Oxygenation-free days to day 28
Measured: 28 Days
Incidence of New Mechanical Ventilation to day 28
Measured: 28 Days
Change in sequential organ failure assessment (SOFA) score from baseline to day 10
Measured: 10 Days
In-hospital adverse events to day 28
Measured: 28 Days
Discontinuation of study drug infusion
Measured: 10 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2020
- Study start1 Sep 2020 (estimated)
- Primary completion31 Dec 2020 (estimated)
- Study completion30 Jan 2021 (estimated)
Why it stopped: Funding not received
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single-center, Phase 2a, pragmatic, randomized, double-blinded, placebo-controlled
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04360876
- Sponsor's protocol ID
- 20-0811
- Status last verified
- Oct 2020
- First submitted
- 22 Apr 2020
- Last updated
- 28 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No Plan
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04360876
- Acronym / sponsor ID
- 20-0811
- Keywords
- Corticosteroids, Dexamethasone, COVID-19 Pneumonia, ARDS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding not received
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 1 Sep 2020 (estimated)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 30 Jan 2021 (estimated)
- First posted
- 24 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- Single-center, Phase 2a, pragmatic, randomized, double-blinded, placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| Dexamethasone | Experimental | Drug: Dexamethasone injectionPatients 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. |
| Placebo | Placebo comparator | Drug: PlacebosParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or Female Adult ≥ 18 years of age at time of enrollment
- Laboratory confirmed SARS-CoV-2 infection determined by PCR within 14 days prior to randomization and no alternative explanation for current clinical condition
- Moderate or Severe ARDS (PaO2:FiO2 ratio ≤ 200mmHg) requiring mechanical ventilation within 7 days prior to randomization
- Hyper-inflammatory ARDS Sub-Phenotype defined as any one of the following:
- Willing and/or able to comply with study-related procedures and assessments
Key exclusion criteria (11 listed)
- Age < 18 years
- In the opinion of the investigator, not expected to survive for more than 48 hours from screening
- Presence of any of the following abnormal laboratory values at screening
- Use of systemic corticosteroid therapy within 7 days of study enrollment
- Known or suspected active bacterial, fungal or mycobacterial infections including tuberculosis (TB)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dexamethasone injectionDexamethasone intravenous 20mg daily for 5 days followed by 10mg daily for 5 days | Drug | Dexamethasone |
| PlacebosPlacebo delivered intravenously on the same dosing schedule as dexamethasone | Drug | Placebo |
Primary outcome
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.
18 secondary outcomes
Clinical Status at day 14 as measured by World Health Organization (WHO) 7-point ordinal scale.
Time frame: 14 Days
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2020.
- Individual participant dataSharing planned: No. No Plan
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dexamethasone injection in people with COVID-19 and ARDS, run by University of Colorado, Denver.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 28 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ventilator Free Days (VFD) at Day 28 (time frame: 28 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2020.