Covid19
Conditions
Keywords
SARS-CoV-2, COVID-19, Placebo, Duke University Health System, Outcomes, Duke Clinical Research Institute, fluticasone, ACTIV 6, ACTIV
Brief summary
The purpose of this study is to evaluate the effectiveness of repurposed medications (study drug(s) in reducing symptoms of non-hospitalized participants with mild to moderate COVID-19. Participants will receive either study drug or placebo. They will self-report any new or worsening symptoms or medical events they may experience while taking study drug or placebo. This study is intended to be all remote with no in person visits, unless the study team feels it is in the best interest of a participant to see them in person. Prior and current drug arms are listed on clinicaltrials.gov and will be updated with the activation of any new drug arms. This protocol was originally registered under NCT04885530. Per recent guidance on reporting master protocol research programs (MPRPs), a separate record for Arm C was created.
Detailed description
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus that first emerged in December 2019 and has since caused a global pandemic unseen in almost a century with respect to the number of cases and overall mortality. The clinical disease related to SARS-CoV-2 is referred to as Coronavirus Disease 2019 (COVID-19). Over 2020, advances were made for treatment of COVID-19 and several vaccinations have received emergency use authorization for prevention of SARS-CoV-2 infections. However, the pandemic continues to evolve with new variants and surges of infections in different regions of the world, requiring an ongoing evidence-generating platform, in particular for the treatment of COVID-19 infection in the outpatient setting. This proposed platform protocol can serve as an evidence generating system for prioritized drugs repurposed from other indications with an established safety record and preliminary evidence of clinical efficacy for the treatment of COVID-19. The ultimate goal is to evaluate if repurposed medications can make participants feel better faster and reduce death and hospitalization. This platform protocol is designed to be flexible so that it is suitable for a wide range of settings within healthcare systems and in community settings where it can be integrated into routine COVID-19 testing programs and subsequent treatment plans. This platform protocol will enroll participants in an outpatient setting with a confirmed polymerase chain reaction (PCR) or antigen test for SARS-CoV-2. Participants will be randomized to study drugs or placebo based on the arms that are actively enrolling at the time of randomization. Study drugs may be added or removed according to adaptive design and/or emerging evidence. When there are multiple study drugs available, randomization will occur based on appropriateness of each drug for the participant as determined by the study protocol and investigator and participant equipoise. Each participant will be required to randomize to at least one study drug versus placebo. Eligible participants will be randomized in a blinded fashion, to either the study drug arm or placebo arm in addition to standard of care. Participants will receive a complete supply study drug or placebo with the quantity depending on the study drug/placebo to which they are randomized. The randomization will be altered to leverage placebo data across arms, and data will be analyzed by shared placebo. All study visits are designed to be remote. However, screening and enrollment may occur in-person at sites and unplanned study visits may occur in-person or remotely, as deemed appropriate by the site investigator for safety purposes. Participants will be asked to complete questionnaires and report safety events during the study. Participants will be prompted by the online system to report safety events and these will be reviewed and confirmed via medical records and site staff, as necessary.
Interventions
DRUGFluticasone
Fluticasone furoate is an inhaled powder drug product composed of fluticasone furoate. It is a synthetic trifluorinated corticosteroid that is insoluble in water. Fluticasone furoate is a white powder and will be provided in a two tone grey inhaler with a mouthpiece cover and separate foil blister strips. The inhaler will be packaged in a moisture-protective foil tray with a desiccant and a peelable lid.All packaging will be labeled to indicate that the product is for investigational use. Participants will self-administer 200 µg (1 blister) of fluticasone furoate once daily for 14 days.
OTHERPlacebo
Each study arm will contain a placebo comparator. Placebo will look similar to study drug and will be administered via the same route of administration and dose. However, placebo will be an inactive substance, containing no study drug.
Sponsors
National Center for Advancing Translational Sciences (NCATS)
Vanderbilt University Medical Center
Susanna Naggie, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
The participant and study teams will know which study drug the participant is allocated to, but will be blinded to study drug versus placebo because they will be matching.
Intervention model description
Double-Blind, Placebo-Controlled, Randomized Trial
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completed Informed Consent * Age ≥ 30 years old * Confirmed SARS-CoV-2 infection by any authorized or approved polymerase chain reaction (PCR) or antigen test collected within 10 days of screening * Two or more current symptoms of acute infection for ≤7 days. Symptoms include the following: fatigue, dyspnea, fever, cough, nausea, vomiting, diarrhea, body aches, chills, headache, sore throat, nasal symptoms, new loss of sense of taste or smell
Exclusion criteria
* Prior diagnosis of COVID-19 infection (\> 10 days from screening) * Current or recent (within 10 days of screening) hospitalization * Current use of study drug or study drug/device combination\* * Known allergy/sensitivity or any hypersensitivity to components of the study drug or placebo\* * Known contraindication(s) to study drug including prohibited concomitant medications\* \[\*If only one study drug appendix is open at the time of enrollment. If multiple study drug appendices are open, a participant may opt-out of any study drug appendix or be excluded from any study drug appendix based on contraindications listed in the study drug appendix, current use of study drug, or known allergy/sensitivity/hypersensitivity and still remain eligible for the remaining study drug appendices.\] Arm-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Sustained Recovery in Days | Up to 28 days | Time to sustained recovery was the number of days between receipt of study drug and the third of 3 consecutive days without symptoms. Participants who died, by definition, did not recover regardless of reported symptom freedom. The reported summary is the median survival time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Mortality | Up to 28 days | — |
| Time to Mortality | Up to 28 days | Time to mortality was the number of days between drug receipt and death. |
| Number of Participants With Hospitalization, Urgent Care, Emergency Room Visit, or Death | Up to 28 days | — |
| Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | Day 7 | COVID Clinical Progression Scale is a scale of 0 to 8 where 0 = No clinical or virological evidence of infection, 1 = No limitation of activities, 2 = Limitation of activities, 3 = Hospitalized, no oxygen therapy, 4 = Hospitalized, on oxygen by mask or nasal prongs, 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen, 6 = Hospitalized, on intubation and mechanical ventilation, 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO), 8 = Death. |
| Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | Day 14 | COVID Clinical Progression Scale is a scale of 0 to 8 where 0 = No clinical or virological evidence of infection, 1 = No limitation of activities, 2 = Limitation of activities, 3 = Hospitalized, no oxygen therapy, 4 = Hospitalized, on oxygen by mask or nasal prongs, 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen, 6 = Hospitalized, on intubation and mechanical ventilation, 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO), 8 = Death. |
| Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | Day 28 | COVID Clinical Progression Scale is a scale of 0 to 8 where 0 = No clinical or virological evidence of infection, 1 = No limitation of activities, 2 = Limitation of activities, 3 = Hospitalized, no oxygen therapy, 4 = Hospitalized, on oxygen by mask or nasal prongs, 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen, 6 = Hospitalized, on intubation and mechanical ventilation, 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO), 8 = Death. |
| Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 7, 14, 28, and 90 | The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a higher score correlates to better outcome for physical function. |
| Number of Participants With Hospitalization or Death | Up to 28 days | — |
| Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 7, 14, 28, and 90 | The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a lower score correlates to better outcome for pain. |
| Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 7, 14, 28, and 90 | The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a lower score correlates to better outcome for depression. |
| Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 7, 14, 28, and 90 | The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20 where a lower score correlates to better outcome for anxiety. |
| Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 7, 14, 28, and 90 | The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20 where a higher score correlates to better outcome for social roles and activities. |
| Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep | Day 7, 14, 28, and 90 | The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20 where a lower score correlates to better outcome for sleep. |
| Time Unwell in Days as Measured by the Symptom and Clinical Event Scale | Up to 14 days | The symptom and clinical event scale is a daily measurement that combines the global symptom burden scale with clinical events hospitalization and mortality. (No symptoms, mild symptoms, moderate symptoms, severe symptoms, hospitalized, deceased). Time unwell was the portion of follow-up (in days) that a participant was symptomatic, hospitalized, or deceased. The quantity is estimated from a Bayesian longitudinal ordinal regression model with covariate adjustment and weakly informative priors. |
| Mean Days Benefit as Measured by the Symptom and Clinical Event Scale | Up to 14 days | The symptom and clinical event scale is a daily measurement that combines the global symptom burden scale with clinical events hospitalization and mortality. (No symptoms, mild symptoms, moderate symptoms, severe symptoms, hospitalized, deceased). The cumulative benefit of treatment A is the probability of experiencing a better outcome on treatment A compared to treatment B, summed over the days of follow-up. The difference between the cumulative benefit of treatment A and the cumulative benefit of treatment B is known as the difference in days benefit. Measure of dispersion is 95% credible interval. |
| Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 7, 14, 28, and 90 | The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a lower score correlates to better outcome for fatigue. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm C - Fluticasone Fluticasone is a self-administered inhaled drug. Participants will self-administer 200 µg (1 blister) of fluticasone once daily for 14 days. After inhaler activation, the powder within the blister is exposed and the participant inhales the study drug through the mouthpiece.
Fluticasone: Fluticasone furoate is an inhaled powder drug product composed of fluticasone furoate. It is a synthetic trifluorinated corticosteroid that is insoluble in water. Fluticasone furoate is a white powder and will be provided in a two tone grey inhaler with a mouthpiece cover and separate foil blister strips. The inhaler will be packaged in a moisture-protective foil tray with a desiccant and a peelable lid.All packaging will be labeled to indicate that the product is for investigational use. Participants will self-administer 200 µg (1 blister) of fluticasone furoate once daily for 14 days. | 656 |
| Arm C - Placebo Placebo is a self-administered inhaled agent. Participants will self-administer 1 blister of placebo once daily for 14 days. After inhaler activation, the powder within the blister is exposed and the participant inhales the placebo through the mouthpiece.
Placebo: Each study arm will contain a placebo comparator. Placebo will look similar to study drug and will be administered via the same route of administration and dose. However, placebo will be an inactive substance, containing no study drug. | 621 |
| Total | 1,277 |
Baseline characteristics
| Characteristic | Arm C - Fluticasone | Arm C - Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45 years | 46 years | 45 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 78 Participants | 83 Participants | 161 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 577 Participants | 537 Participants | 1114 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Race Asian | 29 Participants | 32 Participants | 61 Participants |
| Race/Ethnicity, Customized Race Black, African American, or African | 44 Participants | 40 Participants | 84 Participants |
| Race/Ethnicity, Customized Race Middle Eastern or North African | 12 Participants | 6 Participants | 18 Participants |
| Race/Ethnicity, Customized Race More than one race | 11 Participants | 10 Participants | 21 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Race None of the above | 22 Participants | 16 Participants | 38 Participants |
| Race/Ethnicity, Customized Race No response | 4 Participants | 6 Participants | 10 Participants |
| Race/Ethnicity, Customized Race Prefer not to answer | 17 Participants | 15 Participants | 32 Participants |
| Race/Ethnicity, Customized Race White | 513 Participants | 491 Participants | 1004 Participants |
| Region of Enrollment United States | 656 Participants | 621 Participants | 1277 Participants |
| Sex/Gender, Customized Sex/Gender Female | 431 Participants | 376 Participants | 807 Participants |
| Sex/Gender, Customized Sex/Gender Male | 225 Participants | 243 Participants | 468 Participants |
| Sex/Gender, Customized Sex/Gender Prefer Not to Answer | 0 Participants | 1 Participants | 1 Participants |
| Sex/Gender, Customized Sex/Gender Undifferentiated | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 656 | 0 / 621 |
| other Total, other adverse events | 6 / 656 | 9 / 621 |
| serious Total, serious adverse events | 3 / 656 | 7 / 621 |
Outcome results
Primary
Time to Sustained Recovery in Days
Time to sustained recovery was the number of days between receipt of study drug and the third of 3 consecutive days without symptoms. Participants who died, by definition, did not recover regardless of reported symptom freedom. The reported summary is the median survival time.
Time frame: Up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm C - Fluticasone | Time to Sustained Recovery in Days | 12 days |
| Arm C - Placebo | Time to Sustained Recovery in Days | 13 days |
95% CI: [0.91, 1.12]
Secondary
Mean Days Benefit as Measured by the Symptom and Clinical Event Scale
The symptom and clinical event scale is a daily measurement that combines the global symptom burden scale with clinical events hospitalization and mortality. (No symptoms, mild symptoms, moderate symptoms, severe symptoms, hospitalized, deceased). The cumulative benefit of treatment A is the probability of experiencing a better outcome on treatment A compared to treatment B, summed over the days of follow-up. The difference between the cumulative benefit of treatment A and the cumulative benefit of treatment B is known as the difference in days benefit. Measure of dispersion is 95% credible interval.
Time frame: Up to 14 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm C - Fluticasone | Mean Days Benefit as Measured by the Symptom and Clinical Event Scale | 3.50 days |
| Arm C - Placebo | Mean Days Benefit as Measured by the Symptom and Clinical Event Scale | 3.37 days |
Comparison: Secondary endpoints were not used for formal decision making; there was no decision threshold. No formal hypothesis test was performed.95% CI: [-0.28, 0.58]
Secondary
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14
COVID Clinical Progression Scale is a scale of 0 to 8 where 0 = No clinical or virological evidence of infection, 1 = No limitation of activities, 2 = Limitation of activities, 3 = Hospitalized, no oxygen therapy, 4 = Hospitalized, on oxygen by mask or nasal prongs, 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen, 6 = Hospitalized, on intubation and mechanical ventilation, 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO), 8 = Death.
Time frame: Day 14
Population: Data not collected on 13 participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 1 = No limitation of activities | 566 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen | 1 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 3 = Hospitalized, no oxygen therapy | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 6 = Hospitalized, on intubation and mechanical ventilation | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 2 = Limitation of activities | 19 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO) | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 4 = Hospitalized, on oxygen by mask or nasal prongs | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 8 = Death | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 0 = No clinical or virological evidence of infection | 64 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 8 = Death | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 0 = No clinical or virological evidence of infection | 41 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 1 = No limitation of activities | 547 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 2 = Limitation of activities | 26 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 3 = Hospitalized, no oxygen therapy | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 4 = Hospitalized, on oxygen by mask or nasal prongs | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 6 = Hospitalized, on intubation and mechanical ventilation | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 | 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO) | 0 Participants |
Comparison: Secondary endpoints were not used for formal decision making; there was no decision threshold. No formal hypothesis test was performed.95% CI: [0.42, 1.5]
Secondary
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28
COVID Clinical Progression Scale is a scale of 0 to 8 where 0 = No clinical or virological evidence of infection, 1 = No limitation of activities, 2 = Limitation of activities, 3 = Hospitalized, no oxygen therapy, 4 = Hospitalized, on oxygen by mask or nasal prongs, 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen, 6 = Hospitalized, on intubation and mechanical ventilation, 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO), 8 = Death.
Time frame: Day 28
Population: Data not collected on 107 participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 0 = No clinical or virological evidence of infection | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 2 = Limitation of activities | 11 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 6 = Hospitalized, on intubation and mechanical ventilation | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 1 = No limitation of activities | 579 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO) | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 3 = Hospitalized, no oxygen therapy | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 8 = Death | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 4 = Hospitalized, on oxygen by mask or nasal prongs | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 8 = Death | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 0 = No clinical or virological evidence of infection | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 1 = No limitation of activities | 574 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 2 = Limitation of activities | 6 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 4 = Hospitalized, on oxygen by mask or nasal prongs | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 6 = Hospitalized, on intubation and mechanical ventilation | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO) | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 | 3 = Hospitalized, no oxygen therapy | 0 Participants |
Comparison: Secondary endpoints were not used for formal decision making; there was no decision threshold. No formal hypothesis test was performed.95% CI: [0.5, 5.94]
Secondary
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7
COVID Clinical Progression Scale is a scale of 0 to 8 where 0 = No clinical or virological evidence of infection, 1 = No limitation of activities, 2 = Limitation of activities, 3 = Hospitalized, no oxygen therapy, 4 = Hospitalized, on oxygen by mask or nasal prongs, 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen, 6 = Hospitalized, on intubation and mechanical ventilation, 7 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO), 8 = Death.
Time frame: Day 7
Population: Data not collected on 8 participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 0 = No clinical or virological evidence of infection | 42 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen | 1 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 2 = Limitation of activities | 42 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 6 = Hospitalized, on intubation and mechanical ventilation | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 1 = No limitation of activities | 567 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 07 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO) | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 3 = Hospitalized, no oxygen therapy | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 8 = Death | 0 Participants |
| Arm C - Fluticasone | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 4 = Hospitalized, on oxygen by mask or nasal prongs | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 8 = Death | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 0 = No clinical or virological evidence of infection | 27 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 1 = No limitation of activities | 546 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 2 = Limitation of activities | 43 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 4 = Hospitalized, on oxygen by mask or nasal prongs | 1 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 5 = Hospitalized, on non-invasive ventilation or high-flow oxygen | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 6 = Hospitalized, on intubation and mechanical ventilation | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 07 = Hospitalized, on ventilation + additional organ support (pressors, RRT, ECMO) | 0 Participants |
| Arm C - Placebo | Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 | 3 = Hospitalized, no oxygen therapy | 0 Participants |
Comparison: Secondary endpoints were not used for formal decision making; there was no decision threshold. No formal hypothesis test was performed.95% CI: [0.62, 1.63]
Secondary
Number of Participants With Hospitalization or Death
Time frame: Up to 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm C - Fluticasone | Number of Participants With Hospitalization or Death | 3 Participants |
| Arm C - Placebo | Number of Participants With Hospitalization or Death | 3 Participants |
Comparison: Secondary endpoints were not used for formal decision making; there was no decision threshold. No formal hypothesis test was performed.95% CI: [0.19, 4.68]
Secondary
Number of Participants With Hospitalization, Urgent Care, Emergency Room Visit, or Death
Time frame: Up to 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm C - Fluticasone | Number of Participants With Hospitalization, Urgent Care, Emergency Room Visit, or Death | 24 Participants |
| Arm C - Placebo | Number of Participants With Hospitalization, Urgent Care, Emergency Room Visit, or Death | 13 Participants |
Comparison: Secondary endpoints were not used for formal decision making; there was no decision threshold. No formal hypothesis test was performed.95% CI: [0.8, 3.5]
Secondary
Number of Participants With Mortality
Time frame: Up to 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm C - Fluticasone | Number of Participants With Mortality | 0 Participants |
| Arm C - Placebo | Number of Participants With Mortality | 0 Participants |
Secondary
Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety
The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20 where a lower score correlates to better outcome for anxiety.
Time frame: Day 7, 14, 28, and 90
Population: Participants who responded to the quality of life survey at each timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 7 | 5 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 14 | 4 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 90 | 4 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 28 | 4 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 90 | 4 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 7 | 5 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 14 | 4 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety | Day 28 | 4 score on a scale |
Comparison: Day 795% CI: [0.81, 1.28]
Comparison: Day 1495% CI: [0.6, 0.99]
Comparison: Day 2895% CI: [0.74, 1.23]
Comparison: Day 9095% CI: [0.89, 1.5]
Secondary
Quality of Life (QOL) as Measured by the PROMIS-29 - Depression
The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a lower score correlates to better outcome for depression.
Time frame: Day 7, 14, 28, and 90
Population: Participants who responded to the quality of life survey at each timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 28 | 4 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 7 | 4 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 90 | 4 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 14 | 4 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 90 | 4 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 7 | 4 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 28 | 4 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Depression | Day 14 | 4 score on a scale |
Comparison: Day 795% CI: [0.7, 1.15]
Comparison: Day 1495% CI: [0.75, 1.29]
Comparison: Day 2895% CI: [0.72, 1.26]
Comparison: Day 9095% CI: [0.92, 1.61]
Secondary
Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue
The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a lower score correlates to better outcome for fatigue.
Time frame: Day 7, 14, 28, and 90
Population: Participants who responded to the quality of life survey at each timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 90 | 5 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 7 | 9 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 28 | 5 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 14 | 7 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 28 | 5 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 90 | 4 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 7 | 8 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue | Day 14 | 7 score on a scale |
Comparison: Day 795% CI: [0.72, 1.09]
Comparison: Day 1495% CI: [0.84, 1.27]
Comparison: Day 2895% CI: [0.76, 1.2]
Comparison: Day 9095% CI: [0.84, 1.32]
Secondary
Quality of Life (QOL) as Measured by the PROMIS-29 - Pain
The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a lower score correlates to better outcome for pain.
Time frame: Day 7, 14, 28, and 90
Population: Participants who responded to the quality of life survey at each timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 7 | 6 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 28 | 4 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 14 | 4 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 90 | 4 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 90 | 4 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 7 | 5 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 14 | 4 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Pain | Day 28 | 4 score on a scale |
Comparison: Day 795% CI: [0.58, 0.93]
Comparison: Day 1495% CI: [0.76, 1.32]
Comparison: Day 2895% CI: [0.71, 1.25]
Comparison: Day 9095% CI: [0.89, 1.64]
Secondary
Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function
The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20, where a higher score correlates to better outcome for physical function.
Time frame: Day 7, 14, 28, and 90
Population: Participants who responded to the quality of life survey at each timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 7 | 20 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 14 | 20 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 28 | 20 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 90 | 20 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 90 | 20 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 7 | 20 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 28 | 20 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function | Day 14 | 20 score on a scale |
Comparison: Day 795% CI: [0.69, 1.11]
Comparison: Day 1495% CI: [0.78, 1.34]
Comparison: Day 2895% CI: [0.78, 1.45]
Comparison: Day 9095% CI: [0.79, 1.53]
Secondary
Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep
The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20 where a lower score correlates to better outcome for sleep.
Time frame: Day 7, 14, 28, and 90
Population: Participants who responded to the quality of life survey at each timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep | Day 28 | 8 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep | Day 90 | 8 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep | Day 7 | 10 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep | Day 14 | 9 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep | Day 90 | 8 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep | Day 14 | 9 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep | Day 28 | 8 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep | Day 7 | 10 score on a scale |
Comparison: Day 795% CI: [0.62, 0.93]
Comparison: Day 1495% CI: [0.78, 1.18]
Comparison: Day 2895% CI: [0.74, 1.12]
Comparison: Day 9095% CI: [1.02, 1.56]
Secondary
Quality of Life (QOL) as Measured by the PROMIS-29 - Social
The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance. Raw score ranges from 4-20 where a higher score correlates to better outcome for social roles and activities.
Time frame: Day 7, 14, 28, and 90
Population: Participants who responded to the quality of life survey at each timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 7 | 17 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 14 | 20 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 90 | 20 score on a scale |
| Arm C - Fluticasone | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 28 | 20 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 90 | 20 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 14 | 20 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 28 | 20 score on a scale |
| Arm C - Placebo | Quality of Life (QOL) as Measured by the PROMIS-29 - Social | Day 7 | 17 score on a scale |
Comparison: Day 795% CI: [0.69, 1.06]
Comparison: Day 1495% CI: [0.82, 1.3]
Comparison: Day 2895% CI: [0.8, 1.32]
Comparison: Day 9095% CI: [0.75, 1.29]
Secondary
Time to Mortality
Time to mortality was the number of days between drug receipt and death.
Time frame: Up to 28 days
Population: Data not collected due to no participants with mortality.
Secondary
Time Unwell in Days as Measured by the Symptom and Clinical Event Scale
The symptom and clinical event scale is a daily measurement that combines the global symptom burden scale with clinical events hospitalization and mortality. (No symptoms, mild symptoms, moderate symptoms, severe symptoms, hospitalized, deceased). Time unwell was the portion of follow-up (in days) that a participant was symptomatic, hospitalized, or deceased. The quantity is estimated from a Bayesian longitudinal ordinal regression model with covariate adjustment and weakly informative priors.
Time frame: Up to 14 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm C - Fluticasone | Time Unwell in Days as Measured by the Symptom and Clinical Event Scale | 11.2 days |
| Arm C - Placebo | Time Unwell in Days as Measured by the Symptom and Clinical Event Scale | 11.3 days |
Comparison: Secondary endpoints were not used for formal decision making; there was no decision threshold. No formal hypothesis test was performed.95% CI: [-0.45, 0.26]