Trial Outcomes & Findings for Aerosol Inhalation Treatment for Dyspnea (NCT NCT01440764)

Last Updated: 2017-06-14

Results Overview

Change in breathing discomfort (dyspnea) rating at benchmark PETCO2 using a visual analog scale. The change in breathing discomfort is expressed as units on a 0% to 100% continuous scale, where higher values represent more dyspnea. The change is represented as the rating of breathing discomfort after the intervention minus the rating of breathing discomfort before the intervention.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

24 participants

Primary outcome timeframe

The breathing discomfort ratings were taken as an average of all ratings during runs before intervention and the first two runs after intervention. The 1st and 2nd post-runs began (on average) 12 minutes and 49 minute after intervention, respectively.

Results posted on

2017-06-14

Participant Flow

This was a crossover study of a total of 24 people.

Participant milestones

Participant milestones
Measure	F(40), Then Saline, Then IV.F On Test Day 1, participants received Aerosol Furosemide 40mg in 4ml saline by inhalation for 5-10 minutes. On Test Day 2 (at least 24 hours after Test Day 1), participants received Aerosol Saline 4ml by inhalation for 5-10 minutes. On Test Day 3 (at least 24 hours after Test Day 2), participants received Furosemide 15 mg diluted in 10 ml of saline by intravenous delivery for 5 minutes.	IV.F, Then F(40), Then Saline On Test Day 1, participants received Furosemide 15 mg diluted in 10 ml of saline by intravenous delivery for 5 minutes. On Test Day 2 (at least 24 hours after Test Day 1), participants received Aerosol Furosemide 40mg in 4ml saline by inhalation for 5-10 minutes. On Test Day 3 (at least 24 hours after Test Day 2), participants received Aerosol Saline 4ml by inhalation for 5-10 minutes.	Saline, Then F(40), Then IV.F On Test Day 1, participants received Aerosol Saline 4ml by inhalation for 5-10 minutes. On Test Day 2 (at least 24 hours after Test Day 1), participants received Aerosol Furosemide 40mg in 4ml saline by inhalation for 5-10 minutes. On Test Day 3 (at least 24 hours after Test Day 2), participants received Furosemide 15 mg diluted in 10 ml of saline by intravenous delivery for 5 minutes.	Saline, Then F(80), Then IV.F On Test Day 1, participants received Aerosol Furosemide 80mg in 8ml saline by inhalation for 5-10 minutes. On Test Day 2 (at least 24 hours after Test Day 1), participants received Aerosol Saline 8ml by inhalation for 5-10 minutes. On Test Day 3 (at least 24 hours after Test Day 2), participants received Furosemide 15 mg diluted in 10 ml of saline by intravenous delivery for 5 minutes.	F(80), Then Saline, Then Saline On Test Day 1, participants received Aerosol Furosemide 80mg in 8ml saline by inhalation for 5-10 minutes. On Test Day 2 (at least 24 hours after Test Day 1), participants received Aerosol Saline 8ml by inhalation for 5-10 minutes. On Test Day 3 (at least 24 hours after Test Day 2), participants received Aerosol Saline 8ml by inhalation for 5-10 minutes.	Saline, Then F(80), Then Saline On Test Day 1, participants received Aerosol Saline 8ml by inhalation for 5-10 minutes. On Test Day 2 (at least 24 hours after Test Day 1), participants received Aerosol Furosemide 80mg in 8ml saline by inhalation for 5-10 minutes. On Test Day 3 (at least 24 hours after Test Day 2), participants received Aerosol Saline 8ml by inhalation for 5-10 minutes.	Saline, Then Saline, Then F(80) On Test Day 1, participants received Aerosol Saline 8ml by inhalation for 5-10 minutes. On Test Day 2 (at least 24 hours after Test Day 1), participants received Aerosol Saline 8ml by inhalation for 5-10 minutes. On Test Day 3 (at least 24 hours after Test Day 2), participants received Aerosol Furosemide 80mg in 8ml saline by inhalation for 5-10 minutes.
Test Day 1 STARTED	4	2	6	1	3	5	3
Test Day 1 COMPLETED	4	2	6	1	3	5	3
Test Day 1 NOT COMPLETED	0	0	0	0	0	0	0
Test Day 2 STARTED	3	2	6	1	3	5	3
Test Day 2 COMPLETED	3	2	6	1	3	5	3
Test Day 2 NOT COMPLETED	0	0	0	0	0	0	0
Test Day 3 STARTED	3	2	6	1	3	5	3
Test Day 3 COMPLETED	3	2	6	1	3	5	3
Test Day 3 NOT COMPLETED	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Aerosol Inhalation Treatment for Dyspnea

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	F(40) Participants n=12 Participants Participants who consented to participate in the study and receive the Aerosol Furosemide (40mg/4ml solution of Saline), Aerosol Saline (4ml), and IV Furosemide (15mg/8ml Saline) Interventions in any sequence.	F(80) Participants n=12 Participants Participants who consented to participate in the study and receive the Aerosol Furosemide (80mg/8ml solution of Saline) and two Aerosol Saline (8ml) Interventions in any sequence or receive the Aerosol Furosemide (80mg/8ml solution of Saline), Aerosol Saline (8ml), and IV Furosemide (15mg/8ml Saline) Interventions in any sequence.	Total n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	31.25 years STANDARD_DEVIATION 12.65 • n=5 Participants	23.58 years STANDARD_DEVIATION 4.42 • n=7 Participants	27.42 years STANDARD_DEVIATION 10.06 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	10 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	2 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	12 participants n=7 Participants	24 participants n=5 Participants

PRIMARY outcome

Timeframe: The breathing discomfort ratings were taken as an average of all ratings during runs before intervention and the first two runs after intervention. The 1st and 2nd post-runs began (on average) 12 minutes and 49 minute after intervention, respectively.

Outcome measures

Outcome measures
Measure	Aerosol Furosemide (40 mg) n=11 Participants Participants who received Aerosol Furosemide 40mg in 4ml saline by inhalation for 5-10 minutes on a single test day and met quality control. Of the 12 participants who consented to receive this intervention, all 12 participants received the intervention and completed the study day. However, it was later discovered that 1 subject had used cannabis recently and their information was discarded. Therefore, this analysis includes only the 11 subjects who met quality control.	Aerosol Saline (4 ml) n=10 Participants Participants who received Aerosol Saline (4ml) by inhalation for 5-10 minutes on a single test day and met quality control. Of the 12 participants who consented to receive this intervention, only 11 participants received the intervention and completed the study day (one withdrew before starting this intervention). Additionally, it was later discovered that 1 subject had used cannabis recently and their data was discarded. Therefore, this analysis includes only the 10 subjects who met quality control.	IV Furosemide n=10 Participants Participants who received Furosemide 15 mg diluted in 10 ml of saline by intravenous delivery for 5 minutes on 1 test day and met quality control. Of the 13 participants who consented to receive this intervention, only 12 participants received the intervention and completed the study day (one withdrew before starting this intervention). Additionally, it was later discovered that 1 subject had used cannabis recently and their data was discarded. Also, 1 subject's data did not meet quality control and was excluded. Therefore, this analysis includes only the 10 subjects who met quality control.	Aerosol Furosemide (80mg) n=11 Participants Participants who received Aerosol Furosemide 80mg in 8ml saline by inhalation for 5-10 minutes on 1 test day and met quality control. 12 participants who consented to receive this intervention received the intervention and completed the study day. However, 1 subject's physiological data did not meet quality control and was discarded. Therefore, this analysis includes only the 11 subjects who met quality control.	Aerosol Saline (8 ml) n=11 Participants Aerosol Saline 8ml by inhalation for 5-10 minutes on 2 test days and met quality control. 12 participants who consented to receive this intervention received the intervention and completed the study day. However, 1 subject's physiological data did not meet quality control and was discarded. Therefore, this analysis includes only the 11 subjects who met quality control.
Subject Rating of Breathing Discomfort (Dyspnea)	20 units on a scale Standard Error 13	20 units on a scale Standard Error 10	16 units on a scale Standard Error 13	17 units on a scale Standard Error 3	13 units on a scale Standard Error 4

SECONDARY outcome

Timeframe: Measured before intervention

Characterization of subject's response to laboratory dyspnea model. Data are from a baseline pre-treatment test on the first drug or placebo treatment day for the subjects used in the main analysis. Subjects were asked to complete the MDP with reference to the last 30 sec of each run. To weigh subjects equally, we selected one run from each subject: the first run that terminated in a rating of overall breathing discomfort (A1) of 50 to 90% of full scale. The units of measurement are expressed as units on a 0 to 10 scale measuring intensity of a given quality, with higher values indicating greater intensity and 10 representing maximum perceived intensity.

Outcome measures

Outcome measures
Measure	Aerosol Furosemide (40 mg) n=11 Participants Participants who received Aerosol Furosemide 40mg in 4ml saline by inhalation for 5-10 minutes on a single test day and met quality control. Of the 12 participants who consented to receive this intervention, all 12 participants received the intervention and completed the study day. However, it was later discovered that 1 subject had used cannabis recently and their information was discarded. Therefore, this analysis includes only the 11 subjects who met quality control.	Aerosol Saline (4 ml) n=11 Participants Participants who received Aerosol Saline (4ml) by inhalation for 5-10 minutes on a single test day and met quality control. Of the 12 participants who consented to receive this intervention, only 11 participants received the intervention and completed the study day (one withdrew before starting this intervention). Additionally, it was later discovered that 1 subject had used cannabis recently and their data was discarded. Therefore, this analysis includes only the 10 subjects who met quality control.	IV Furosemide Participants who received Furosemide 15 mg diluted in 10 ml of saline by intravenous delivery for 5 minutes on 1 test day and met quality control. Of the 13 participants who consented to receive this intervention, only 12 participants received the intervention and completed the study day (one withdrew before starting this intervention). Additionally, it was later discovered that 1 subject had used cannabis recently and their data was discarded. Also, 1 subject's data did not meet quality control and was excluded. Therefore, this analysis includes only the 10 subjects who met quality control.	Aerosol Furosemide (80mg) Participants who received Aerosol Furosemide 80mg in 8ml saline by inhalation for 5-10 minutes on 1 test day and met quality control. 12 participants who consented to receive this intervention received the intervention and completed the study day. However, 1 subject's physiological data did not meet quality control and was discarded. Therefore, this analysis includes only the 11 subjects who met quality control.	Aerosol Saline (8 ml) Aerosol Saline 8ml by inhalation for 5-10 minutes on 2 test days and met quality control. 12 participants who consented to receive this intervention received the intervention and completed the study day. However, 1 subject's physiological data did not meet quality control and was discarded. Therefore, this analysis includes only the 11 subjects who met quality control.
Multidimensional Dyspnea Profile A1 (overall breathing discomfort)	8.0 units on a scale Standard Error 0.2	6.4 units on a scale Standard Error 0.4	—	—	—
Multidimensional Dyspnea Profile Muscle Work	5.5 units on a scale Standard Error 0.8	2.5 units on a scale Standard Error 0.7	—	—	—
Multidimensional Dyspnea Profile Air hunger	7.4 units on a scale Standard Error 0.5	6.2 units on a scale Standard Error 0.8	—	—	—
Multidimensional Dyspnea Profile Tightness	3.3 units on a scale Standard Error 0.8	2.6 units on a scale Standard Error 0.9	—	—	—
Multidimensional Dyspnea Profile Mental effort	6.3 units on a scale Standard Error 0.7	3.6 units on a scale Standard Error 0.9	—	—	—
Multidimensional Dyspnea Profile Breathing a lot	4.0 units on a scale Standard Error 0.9	1.5 units on a scale Standard Error 0.7	—	—	—
Multidimensional Dyspnea Profile Depressed	0.3 units on a scale Standard Error 0.2	0.0 units on a scale Standard Error 0.0	—	—	—
Multidimensional Dyspnea Profile Anxious	3.7 units on a scale Standard Error 0.7	2.9 units on a scale Standard Error 0.6	—	—	—
Multidimensional Dyspnea Profile Frustrated	1.6 units on a scale Standard Error 0.7	1.6 units on a scale Standard Error 0.6	—	—	—
Multidimensional Dyspnea Profile Angry	0.9 units on a scale Standard Error 0.5	0.2 units on a scale Standard Error 0.2	—	—	—
Multidimensional Dyspnea Profile Afraid	1.1 units on a scale Standard Error 0.4	1.2 units on a scale Standard Error 0.4	—	—	—

SECONDARY outcome

Timeframe: Cumulative urine output 1 hour after intervention

Diuresis is an expected effect of furosemide. To the extent that aerosol furosemide is absorbed into the blood, diuresis is an expected 'side effect' of this treatment