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Aerosol Inhalation Treatment for Dyspnea

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ClinicalTrials.gov Identifier: NCT01440764
Recruitment Status : Completed
First Posted : September 27, 2011
Results First Posted : June 14, 2017
Last Update Posted : June 14, 2017
Sponsor:
Collaborator:
National Institute of Nursing Research (NINR)
Information provided by (Responsible Party):
Robert Banzett, Beth Israel Deaconess Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Basic Science
Conditions Healthy
Dyspnea
Interventions Drug: Furosemide
Drug: Saline
Enrollment 24
Recruitment Details  
Pre-assignment Details This was a crossover study of a total of 24 people.
Arm/Group Title F(40), Then Saline, Then IV.F IV.F, Then F(40), Then Saline Saline, Then F(40), Then IV.F Saline, Then F(80), Then IV.F F(80), Then Saline, Then Saline Saline, Then F(80), Then Saline Saline, Then Saline, Then F(80)
Hide Arm/Group Description

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.

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.

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.

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.

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.

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.

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.

Period Title: Test Day 1
Started 4 2 6 1 3 5 3
Completed 4 2 6 1 3 5 3
Not Completed 0 0 0 0 0 0 0
Period Title: Test Day 2
Started 3 [1] 2 6 1 3 5 3
Completed 3 2 6 1 3 5 3
Not Completed 0 0 0 0 0 0 0
[1]
Following Test Day 1, 1 subject withdrew from the study before beginning Test Day 2.
Period Title: Test Day 3
Started 3 2 6 1 3 5 3
Completed 3 2 6 1 3 5 3
Not Completed 0 0 0 0 0 0 0
Arm/Group Title F(40) Participants F(80) Participants Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 12 12 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 24 participants
<=18 years
0
   0.0%
1
   8.3%
1
   4.2%
Between 18 and 65 years
12
 100.0%
11
  91.7%
23
  95.8%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 12 participants 24 participants
31.25  (12.65) 23.58  (4.42) 27.42  (10.06)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 24 participants
Female
3
  25.0%
10
  83.3%
13
  54.2%
Male
9
  75.0%
2
  16.7%
11
  45.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 12 participants 12 participants 24 participants
12 12 24
1.Primary Outcome
Title Subject Rating of Breathing Discomfort (Dyspnea)
Hide Description 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.
Time Frame 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aerosol Furosemide (40 mg) Aerosol Saline (4 ml) IV Furosemide Aerosol Furosemide (80mg) Aerosol Saline (8 ml)
Hide Arm/Group Description:

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.

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.

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.

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 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.

Overall Number of Participants Analyzed 11 10 10 11 11
Mean (Standard Error)
Unit of Measure: units on a scale
20  (13) 20  (10) 16  (13) 17  (3) 13  (4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aerosol Furosemide (40 mg), Aerosol Saline (4 ml)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.99
Comments a priori threshold for significance was 0.05. Not corrected for multiple comparisons. This p-value describes the a priori analysis of comparing the furosemide test result to the saline test result.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Aerosol Furosemide (80mg), Aerosol Saline (8 ml)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments a priori threshold for significance was 0.05. Not corrected for multiple comparisons. Thes p-value describes the a priori analysis of comparing the response to furosemide to the mean response to saline.
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Multidimensional Dyspnea Profile
Hide Description 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.
Time Frame Measured before intervention
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aerosol Furosemide (40 mg) Aerosol Furosemide (80mg)
Hide Arm/Group Description:

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.

Participants who received Aerosol Furosemide 80mg in 8ml 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's data did not pass a priori requirements for quality control and the subject's data was excluded. Therefore, this analysis includes only the 11 subjects who met quality control.

Overall Number of Participants Analyzed 11 11
Mean (Standard Error)
Unit of Measure: units on a scale
A1 (overall breathing discomfort) 8.0  (0.2) 6.4  (0.4)
Muscle Work 5.5  (0.8) 2.5  (0.7)
Air hunger 7.4  (0.5) 6.2  (0.8)
Tightness 3.3  (0.8) 2.6  (0.9)
Mental effort 6.3  (0.7) 3.6  (0.9)
Breathing a lot 4.0  (0.9) 1.5  (0.7)
Depressed 0.3  (0.2) 0.0  (0.0)
Anxious 3.7  (0.7) 2.9  (0.6)
Frustrated 1.6  (0.7) 1.6  (0.6)
Angry 0.9  (0.5) 0.2  (0.2)
Afraid 1.1  (0.4) 1.2  (0.4)
3.Secondary Outcome
Title Urine Output
Hide Description 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
Time Frame Cumulative urine output 1 hour after intervention
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aerosol Furosemide (40 mg) Aerosol Furosemide (80mg) Aerosol Saline (4 ml) Aerosol Saline (8 ml) IV Furosemide
Hide Arm/Group Description:

Aerosol Furosemide 40mg in 4ml saline by inhalation for 5-10 minutes on 1 test day.

To be compared to Aerosol Saline (4ml) Arm and IV Furosemide Arm.

Furosemide

Aerosol Furosemide 80mg in 8ml saline by inhalation for 5-10 minutes on 1 test day.

To be compared to Aerosol Saline (8ml) Arm.

Furosemide

Aerosol Saline 4ml by inhalation for 5-10 minutes on 1 test day.

To be compared to Aerosol Furosemide (40mg) Arm and IV Furosemide Arm.

Saline

Aerosol Saline 8ml by inhalation for 5-10 minutes on 2 test days.

To be compared to Aerosol Furosemide (80mg) Arm.

Saline

Furosemide 15 mg diluted in 10 ml of saline by intravenous delivery for 5 minutes on 1 test day.

To be compared to Aerosol Furosemide (40mg) Arm and Aerosol Saline (4 ml) Arm.

Furosemide

Overall Number of Participants Analyzed 12 11 10 11 11
Mean (Standard Deviation)
Unit of Measure: ml of urine
1069  (435) 1320  (394) 500  (264) 474  (146) 1556  (435)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aerosol Furosemide (40 mg), Aerosol Saline (4 ml)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0006
Comments a priori threshold for statistical significance was 0.05. Not adjusted for multiple comparisons.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Aerosol Furosemide (80mg), Aerosol Saline (8 ml)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =.00001
Comments a priori threshold for statistical significance was 0.05. Not adjusted for multiple comparisons.
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Aerosol Saline (4 ml), IV Furosemide
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0000002
Comments a priori threshold for significance was 0.05. Not adjusted for multiple comparisons.
Method t-test, 2 sided
Comments [Not Specified]
Time Frame 1 year
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Aerosol Furosemide (40 mg) Aerosol Furosemide (80mg) Aerosol Saline (4 ml) Aerosol Saline (8 ml) IV Furosemide
Hide Arm/Group Description Any subject who received Aerosol Furosemide 40mg in 4ml saline by inhalation for 5-10 minutes on 1 test day. Any subject who received Aerosol Furosemide 80mg in 8ml saline by inhalation for 5-10 minutes on 1 test day. Any subject who received Aerosol Saline 4ml by inhalation for 5-10 minutes on 1 test day. Any subject who received Aerosol Saline 8ml by inhalation for 5-10 minutes on 2 test days. Any subject who received Furosemide 15 mg diluted in 10 ml of saline by intravenous delivery for 5 minutes on 1 test day.
All-Cause Mortality
Aerosol Furosemide (40 mg) Aerosol Furosemide (80mg) Aerosol Saline (4 ml) Aerosol Saline (8 ml) IV Furosemide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)   0/12 (0.00%)   0/11 (0.00%)   0/12 (0.00%)   0/12 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Aerosol Furosemide (40 mg) Aerosol Furosemide (80mg) Aerosol Saline (4 ml) Aerosol Saline (8 ml) IV Furosemide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)   0/12 (0.00%)   0/11 (0.00%)   0/12 (0.00%)   0/12 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Aerosol Furosemide (40 mg) Aerosol Furosemide (80mg) Aerosol Saline (4 ml) Aerosol Saline (8 ml) IV Furosemide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)   0/12 (0.00%)   0/11 (0.00%)   0/11 (0.00%)   0/12 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Robert Banzett, PhD
Organization: Beth Israel Deaconess Medical Center
Phone: (617)667-0572
Responsible Party: Robert Banzett, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01440764     History of Changes
Other Study ID Numbers: 2011-P-000027/1
R01NR012009 ( U.S. NIH Grant/Contract )
First Submitted: September 23, 2011
First Posted: September 27, 2011
Results First Submitted: April 11, 2017
Results First Posted: June 14, 2017
Last Update Posted: June 14, 2017