Trial Outcomes & Findings for ACTIV-6: COVID-19 Study of Repurposed Medications - Arm C (Fluticasone) (NCT NCT05736874)

NCT ID: NCT05736874

Last Updated: 2023-06-18

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1407 participants
• Primary outcome timeframe: Up to 28 days
• Results posted on: 2023-06-18

Participant Flow

Participant milestones

Measure	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.	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.
Overall Study STARTED	715	692
Overall Study COMPLETED	656	621
Overall Study NOT COMPLETED	59	71

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

ACTIV-6: COVID-19 Study of Repurposed Medications - Arm C (Fluticasone)

Baseline characteristics by cohort

Measure	Arm C - Fluticasone n=656 Participants 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.	Arm C - Placebo n=621 Participants 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.	Total n=1277 Participants Total of all reporting groups
Age, Continuous	45 years n=5 Participants	46 years n=7 Participants	45 years n=5 Participants
Sex/Gender, Customized Sex/Gender · Female	431 Participants n=5 Participants	376 Participants n=7 Participants	807 Participants n=5 Participants
Sex/Gender, Customized Sex/Gender · Male	225 Participants n=5 Participants	243 Participants n=7 Participants	468 Participants n=5 Participants
Sex/Gender, Customized Sex/Gender · Undifferentiated	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex/Gender, Customized Sex/Gender · Prefer Not to Answer	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	78 Participants n=5 Participants	83 Participants n=7 Participants	161 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	577 Participants n=5 Participants	537 Participants n=7 Participants	1114 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	29 Participants n=5 Participants	32 Participants n=7 Participants	61 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black, African American, or African	44 Participants n=5 Participants	40 Participants n=7 Participants	84 Participants n=5 Participants
Race/Ethnicity, Customized Race · Middle Eastern or North African	12 Participants n=5 Participants	6 Participants n=7 Participants	18 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	513 Participants n=5 Participants	491 Participants n=7 Participants	1004 Participants n=5 Participants
Race/Ethnicity, Customized Race · More than one race	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Race/Ethnicity, Customized Race · None of the above	22 Participants n=5 Participants	16 Participants n=7 Participants	38 Participants n=5 Participants
Race/Ethnicity, Customized Race · Prefer not to answer	17 Participants n=5 Participants	15 Participants n=7 Participants	32 Participants n=5 Participants
Race/Ethnicity, Customized Race · No response	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment United States	656 Participants n=5 Participants	621 Participants n=7 Participants	1277 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Arm C - Fluticasone n=656 Participants 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.	Arm C - Placebo n=621 Participants 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.
Time to Sustained Recovery in Days	12 days Interval 12.0 to 13.0	13 days Interval 12.0 to 14.0

SECONDARY outcome

Timeframe: Up to 28 days

Outcome measures

Measure	Arm C - Fluticasone n=656 Participants 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.	Arm C - Placebo n=621 Participants 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.
Number of Participants With Hospitalization or Death	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 28 days

Outcome measures

Measure	Arm C - Fluticasone n=656 Participants 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.	Arm C - Placebo n=621 Participants 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.
Number of Participants With Mortality	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 28 days

Population: Data not collected due to no participants with mortality.

Time to mortality was the number of days between drug receipt and death.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 28 days

Outcome measures

Measure	Arm C - Fluticasone n=656 Participants 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.	Arm C - Placebo n=621 Participants 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.
Number of Participants With Hospitalization, Urgent Care, Emergency Room Visit, or Death	24 Participants	13 Participants

SECONDARY outcome

Timeframe: Day 7

Population: Data not collected on 8 participants.

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.

Outcome measures

Measure	Arm C - Fluticasone n=652 Participants 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.	Arm C - Placebo n=617 Participants 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.
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	27 Participants
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 1 = No limitation of activities	567 Participants	546 Participants
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 2 = Limitation of activities	42 Participants	43 Participants
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 3 = Hospitalized, no oxygen therapy	0 Participants	0 Participants
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	1 Participants
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	0 Participants
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 6 = Hospitalized, on intubation and mechanical ventilation	0 Participants	0 Participants
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	0 Participants
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 7 8 = Death	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 14

Population: Data not collected on 13 participants.

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.

Outcome measures

Measure	Arm C - Fluticasone n=650 Participants 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.	Arm C - Placebo n=614 Participants 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.
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 8 = Death	0 Participants	0 Participants
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	41 Participants
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 1 = No limitation of activities	566 Participants	547 Participants
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 2 = Limitation of activities	19 Participants	26 Participants
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 3 = Hospitalized, no oxygen therapy	0 Participants	0 Participants
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	0 Participants
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	0 Participants
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 14 6 = Hospitalized, on intubation and mechanical ventilation	0 Participants	0 Participants
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	0 Participants

SECONDARY outcome

Timeframe: Day 28

Population: Data not collected on 107 participants.

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.

Outcome measures

Measure	Arm C - Fluticasone n=590 Participants 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.	Arm C - Placebo n=580 Participants 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.
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	0 Participants
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 1 = No limitation of activities	579 Participants	574 Participants
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 2 = Limitation of activities	11 Participants	6 Participants
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 3 = Hospitalized, no oxygen therapy	0 Participants	0 Participants
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	0 Participants
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	0 Participants
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 6 = Hospitalized, on intubation and mechanical ventilation	0 Participants	0 Participants
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	0 Participants
Number of Participants at Each Score on the COVID Clinical Progression Scale at Day 28 8 = Death	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 7, 14, 28, and 90

Population: Participants who responded to the quality of life survey at each timepoint.

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.

Outcome measures

Measure	Arm C - Fluticasone n=656 Participants 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.	Arm C - Placebo n=621 Participants 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.
Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function Day 7	20 score on a scale Interval 17.0 to 20.0	20 score on a scale Interval 16.0 to 20.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function Day 14	20 score on a scale Interval 19.0 to 20.0	20 score on a scale Interval 19.0 to 20.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function Day 28	20 score on a scale Interval 20.0 to 20.0	20 score on a scale Interval 20.0 to 20.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Physical Function Day 90	20 score on a scale Interval 20.0 to 20.0	20 score on a scale Interval 20.0 to 20.0

SECONDARY outcome

Timeframe: Day 7, 14, 28, and 90

Population: Participants who responded to the quality of life survey at each timepoint.

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.

Outcome measures

Measure	Arm C - Fluticasone n=656 Participants 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.	Arm C - Placebo n=621 Participants 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.
Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue Day 7	9 score on a scale Interval 7.0 to 13.0	8 score on a scale Interval 7.0 to 12.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue Day 14	7 score on a scale Interval 4.0 to 9.0	7 score on a scale Interval 4.0 to 9.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue Day 28	5 score on a scale Interval 4.0 to 8.0	5 score on a scale Interval 4.0 to 8.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Fatigue Day 90	5 score on a scale Interval 4.0 to 8.0	4 score on a scale Interval 4.0 to 8.0

SECONDARY outcome

Timeframe: Day 7, 14, 28, and 90

Population: Participants who responded to the quality of life survey at each timepoint.

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.

Outcome measures

Measure	Arm C - Fluticasone n=656 Participants 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.	Arm C - Placebo n=621 Participants 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.
Quality of Life (QOL) as Measured by the PROMIS-29 - Pain Day 7	6 score on a scale Interval 4.0 to 9.0	5 score on a scale Interval 4.0 to 8.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Pain Day 14	4 score on a scale Interval 4.0 to 6.0	4 score on a scale Interval 4.0 to 6.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Pain Day 28	4 score on a scale Interval 4.0 to 4.0	4 score on a scale Interval 4.0 to 4.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Pain Day 90	4 score on a scale Interval 4.0 to 4.0	4 score on a scale Interval 4.0 to 4.0

SECONDARY outcome

Timeframe: Day 7, 14, 28, and 90

Population: Participants who responded to the quality of life survey at each timepoint.

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.

Outcome measures

Measure	Arm C - Fluticasone n=656 Participants 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.	Arm C - Placebo n=621 Participants 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.
Quality of Life (QOL) as Measured by the PROMIS-29 - Depression Day 7	4 score on a scale Interval 4.0 to 6.0	4 score on a scale Interval 4.0 to 6.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Depression Day 14	4 score on a scale Interval 4.0 to 5.0	4 score on a scale Interval 4.0 to 5.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Depression Day 28	4 score on a scale Interval 4.0 to 5.0	4 score on a scale Interval 4.0 to 5.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Depression Day 90	4 score on a scale Interval 4.0 to 5.0	4 score on a scale Interval 4.0 to 5.0

SECONDARY outcome

Timeframe: Day 7, 14, 28, and 90

Population: Participants who responded to the quality of life survey at each timepoint.

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.

Outcome measures

Measure	Arm C - Fluticasone n=656 Participants 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.	Arm C - Placebo n=621 Participants 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.
Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety Day 7	5 score on a scale Interval 4.0 to 8.0	5 score on a scale Interval 4.0 to 8.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety Day 14	4 score on a scale Interval 4.0 to 6.0	4 score on a scale Interval 4.0 to 6.5
Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety Day 28	4 score on a scale Interval 4.0 to 6.0	4 score on a scale Interval 4.0 to 6.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Anxiety Day 90	4 score on a scale Interval 4.0 to 6.0	4 score on a scale Interval 4.0 to 6.0

SECONDARY outcome

Timeframe: Day 7, 14, 28, and 90

Population: Participants who responded to the quality of life survey at each timepoint.

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.

Outcome measures

Measure	Arm C - Fluticasone n=656 Participants 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.	Arm C - Placebo n=621 Participants 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.
Quality of Life (QOL) as Measured by the PROMIS-29 - Social Day 7	17 score on a scale Interval 13.0 to 20.0	17 score on a scale Interval 14.0 to 20.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Social Day 14	20 score on a scale Interval 16.0 to 20.0	20 score on a scale Interval 16.0 to 20.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Social Day 28	20 score on a scale Interval 18.0 to 20.0	20 score on a scale Interval 17.0 to 20.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Social Day 90	20 score on a scale Interval 18.0 to 20.0	20 score on a scale Interval 18.0 to 20.0

SECONDARY outcome

Timeframe: Day 7, 14, 28, and 90

Population: Participants who responded to the quality of life survey at each timepoint.

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.

Outcome measures

Measure	Arm C - Fluticasone n=656 Participants 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.	Arm C - Placebo n=621 Participants 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.
Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Day 7	10 score on a scale Interval 8.0 to 13.0	10 score on a scale Interval 7.0 to 12.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Day 14	9 score on a scale Interval 6.0 to 11.0	9 score on a scale Interval 6.0 to 12.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Day 28	8 score on a scale Interval 6.0 to 11.0	8 score on a scale Interval 6.0 to 11.0
Quality of Life (QOL) as Measured by the PROMIS-29 - Sleep Day 90	8 score on a scale Interval 6.0 to 11.0	8 score on a scale Interval 6.0 to 11.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Arm C - Fluticasone n=656 Participants 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.	Arm C - Placebo n=621 Participants 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.
Time Unwell in Days as Measured by the Symptom and Clinical Event Scale	11.2 days Interval 11.0 to 11.4	11.3 days Interval 11.1 to 11.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Arm C - Fluticasone n=656 Participants 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.	Arm C - Placebo n=621 Participants 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.
Mean Days Benefit as Measured by the Symptom and Clinical Event Scale	3.50 days Interval 3.28 to 3.73	3.37 days Interval 3.16 to 3.6

Adverse Events

Arm C - Fluticasone

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Arm C - Placebo

Serious events: 7 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm C - Fluticasone n=656 participants at risk 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.	Arm C - Placebo n=621 participants at risk 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.
General disorders Adverse drug reaction	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Vascular disorders Coronary vasospasm	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Infections and infestations COVID-19 pneumonia	0.15% 1/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Infections and infestations COVID-19 pneumonia aggravated	0.30% 2/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.00% 0/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Eye disorders Diplopia	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Gastrointestinal disorders Nausea and vomiting symptoms	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Infections and infestations Urinary tract infection	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Eye disorders Opthalmic migraine	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.

Other adverse events

Measure	Arm C - Fluticasone n=656 participants at risk 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.	Arm C - Placebo n=621 participants at risk 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.
Skin and subcutaneous tissue disorders Accelerated hair loss	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Psychiatric disorders Anxiety	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
General disorders Chest tightness	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Respiratory, thoracic and mediastinal disorders Cough	0.15% 1/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.00% 0/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Infections and infestations COVID-19 pneumonia	0.15% 1/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.00% 0/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Gastrointestinal disorders Diarrhea	0.15% 1/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.00% 0/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
General disorders Fever	0.15% 1/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.00% 0/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Gastrointestinal disorders GERD	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.15% 1/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Nervous system disorders Insomnia	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.48% 3/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Nervous system disorders Loss of smell	0.15% 1/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.00% 0/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Gastrointestinal disorders Loss of taste	0.15% 1/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.00% 0/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Cardiac disorders Palpitations	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Immune system disorders Seasonal allergy	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Respiratory, thoracic and mediastinal disorders Sinusitis	0.15% 1/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.00% 0/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Respiratory, thoracic and mediastinal disorders Sneezing	0.15% 1/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.00% 0/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
General disorders Swelling	0.15% 1/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.00% 0/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Gastrointestinal disorders Constipation	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.
Cardiac disorders Elevated Pulse	0.00% 0/656 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.	0.16% 1/621 • Up to 90 days Participants were asked to complete daily assessments and report adverse events via the study portal through day 14, then at other intervals through day 28, and at the final study visit at day 90. Adverse event tables were updated on 5/18/2023 to reflect data cleaning and data monitoring efforts by contributing sites. Some sites determined that some previously reported events should not have been reported per the criteria noted in the protocol.

Additional Information

Susanna Naggie, MD, MHS, FIDSA

Duke University

Phone: 919-684-2584

Email: susanna.naggie@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place