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| ID | Type | Description | Link |
|---|---|---|---|
| R01NR012009 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Nursing Research (NINR) | NIH |
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The purpose of this protocol is to develop and test optimal delivery of aerosol furosemide, a treatment that has the potential to significantly improve symptom management and enhance the quality of care for patients with intractable dyspnea.
This is study of aerosol treatment in a laboratory model of dyspnea in healthy subjects. This study is the first in a series of studies that will include investigation of a second dose in the laboratory and investigation of the treatment effect in hospitalized patients with refractory dyspnea. The outcome of this first study will determine the details of protocol for the succeeding studies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| F(40), then Saline, then IV.F | Experimental | 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 | Experimental | 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 | Experimental | 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 3), 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. |
|
| F(80), then Saline, then Saline | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Furosemide | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Subject Rating of Breathing Discomfort (Dyspnea) | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Multidimensional Dyspnea Profile | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert B Banzett, PhD | Beth Israel Deaconess Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21778294 | Background | Banzett RB, Adams L, O'Donnell CR, Gilman SA, Lansing RW, Schwartzstein RM. Using laboratory models to test treatment: morphine reduces dyspnea and hypercapnic ventilatory response. Am J Respir Crit Care Med. 2011 Oct 15;184(8):920-7. doi: 10.1164/rccm.201101-0005OC. Epub 2011 Jul 21. |
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This was a crossover study of a total of 24 people.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | 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. |
| FG006 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Test Day 1 |
| |||||||||||||
| Test Day 2 |
| |||||||||||||
| Test Day 3 |
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| ID | Title | Description |
|---|---|---|
| BG000 | F(40) 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. |
| BG001 | F(80) Participants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Subject Rating of Breathing Discomfort (Dyspnea) | 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. | Posted | Mean | Standard Error | units on a scale | 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. |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Aerosol Furosemide (40 mg) | Any subject who received Aerosol Furosemide 40mg in 4ml saline by inhalation for 5-10 minutes on 1 test day. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Robert Banzett, PhD | Beth Israel Deaconess Medical Center | (617)667-0572 | rbanzett@bidmc.harvard.edu |
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| ID | Term |
|---|---|
| D004417 | Dyspnea |
| ID | Term |
|---|---|
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D005665 | Furosemide |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D013424 | Sulfanilamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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|
| Saline, then F(80), then Saline | Experimental | 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) | Experimental | 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. |
|
|
| Saline | Drug |
|
| Measured before intervention |
| Urine Output | 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 | Cumulative urine output 1 hour after intervention |
| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
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| NOT COMPLETED |
|
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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Aerosol Saline (4 ml) | 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. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
|
|
|
| Secondary | Multidimensional Dyspnea Profile | 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. | Posted | Mean | Standard Error | units on a scale | Measured before intervention |
|
|
|
| Secondary | Urine Output | 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 | Posted | Mean | Standard Deviation | ml of urine | Cumulative urine output 1 hour after intervention |
|
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | Aerosol Furosemide (80mg) | Any subject who received Aerosol Furosemide 80mg in 8ml saline by inhalation for 5-10 minutes on 1 test day. | 0 | 12 | 0 | 12 | 0 | 12 |
| EG002 | Aerosol Saline (4 ml) | Any subject who received Aerosol Saline 4ml by inhalation for 5-10 minutes on 1 test day. | 0 | 11 | 0 | 11 | 0 | 11 |
| EG003 | Aerosol Saline (8 ml) | Any subject who received Aerosol Saline 8ml by inhalation for 5-10 minutes on 2 test days. | 0 | 12 | 0 | 12 | 0 | 11 |
| EG004 | IV Furosemide | Any subject who received Furosemide 15 mg diluted in 10 ml of saline by intravenous delivery for 5 minutes on 1 test day. | 0 | 12 | 0 | 12 | 0 | 12 |
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| D013568 | Pathological Conditions, Signs and Symptoms |
| D000814 |
| Aniline Compounds |
| D000588 | Amines |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| Air hunger |
|
| Tightness |
|
| Mental effort |
|
| Breathing a lot |
|
| Depressed |
|
| Anxious |
|
| Frustrated |
|
| Angry |
|
| Afraid |
|
| =.00001 |
a priori threshold for statistical significance was 0.05. Not adjusted for multiple comparisons. |
| Superiority |
| t-test, 2 sided | .0000002 | a priori threshold for significance was 0.05. Not adjusted for multiple comparisons. | Superiority |