Dyspnea
Conditions
Keywords
Dyspnea, Hospitalized patients, Ambulatory outpatients, Shortness of breath, Chronic obstructive pulmonary disease, Pulmonary disease
Brief summary
The purpose of this protocol is to develop and test aerosol furosemide, as a treatment that has the potential to significantly improve symptom management and enhance the quality of care for patients with intractable dyspnea.
Detailed description
This is the second study in a series of studies investigating the treatment effect of aerosolized furosemide on hospitalized patients and outpatients with intractable dyspnea. The study will focus on patients who experience intractable dyspnea at rest or with minimal activity, e.g., dressing, bathing, cooking, or walking stairs or short distances. There are two parts to this study: Study 2a is a pilot study on 5-10 patients. These trials are not blinded or placebo controlled; the investigators will use them to discover practical problems, and take the information back to the laboratory to develop solutions. We enrolled 7 subjects for Study 2a. Study 2b will a randomized, placebo - controlled, double- blind study on 25 - 40 patients. The two planned treatments will be aerosolized furosemide and aerosolized saline, and will be given to each patient on two separate days. We failed to reach our enrollment goal, and ultimately enrolled 17 subjects for participation in Study 2b.
Interventions
DRUGFurosemide
80 mg of Furosemide in 8ml saline will be aerosolized using ultrasonic screen nebulizers. Aerosol will be delivered using a clinical volume-control ventilator to regulate inspiratory flow and volume.
DRUGAerosolized saline
8ml saline will be aerosolized using ultrasonic screen nebulizers. Aerosol will be delivered using a clinical volume-control ventilator to regulate inspiratory flow and volume.
Sponsors
National Institute of Nursing Research (NINR)
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Intractable dyspnea at rest or with minimal activity
Exclusion criteria
* Chronic congestive heart failure * Liver or kidney disease * Systemic lupus erythematosis (SLE) * Receiving potassium supplementation or other indication of hypokalemia * Major psychiatric disorders * Furosemide hypersensitivity * Not mentally competent and/or alert (unable to grant informed consent) * Under 18 years old * Not fluent in English * Inadequate birth control
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Subject Rating of Breathing Discomfort (Dyspnea) Before and After Treatment. | 15 min | Subjects will rate breathing discomfort (dyspnea) during a 15 min exercise test using a visual analog scale before and after drug (or placebo) intervention. The treatment effect was measured as the rating of breathing discomfort rating before treatment minus the rating of breathing discomfort after treatment at equivalent work intensities. Outcome Measure Time Frame: subjects performed arm exercise to induce dyspnea for approximately 15 min before and after aerosol inhalation. the average number of minutes between end of drug administration and post-intervention breathing discomfort rating: Aerosol furosemide Study 2a arm: 38.7 minutes; Aerosol furosemide Study 2b arm: 21.8 minutes; Aerosol saline Study 2b arm: 21.3 minutes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urine Output - mL | Summation of total urine output (mL) at 1 hour following drug administration. | Diuresis is an expected effect of furosemide. To the extent that aerosol furosemide is absorbed in the blood, diuresis is an expected 'side effect' of this treatment. Following intervention, study team will measure urine output (mL). Study team will then rehydrate subject with an equal amount of liquid to their output. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aerosol Furosemide Study 2a Subjects will inhale 40mg of furosemide aerosol over the course of 10-15 min. This will be a single, unblinded administration. | 7 |
| Aerosol Furosemide Study 2b Inhalation of furosemide aerosol or placebo saline aerosol over the course of 10-15 min. Single administration of furosemide aerosol on one treatment day, and a single administration of saline aerosol on a separate treatment day. Order of Furosemide Treatment Day and Placebo Treatment Day is randomized. | 17 |
| Total | 24 |
Baseline characteristics
| Characteristic | Aerosol Furosemide Study 2a | Aerosol Furosemide Study 2b | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 12 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 5 Participants | 8 Participants |
| Age, Continuous | 69.14 years STANDARD_DEVIATION 11.09 | 67.41 years STANDARD_DEVIATION 11.41 | 67.92 years STANDARD_DEVIATION 11.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 16 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 13 Participants | 19 Participants |
| Region of Enrollment United States | 7 participants | 17 participants | 24 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 4 Participants | 13 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 17 | 0 / 17 |
| other Total, other adverse events | 0 / 7 | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 7 | 0 / 17 | 0 / 17 |
Outcome results
Primary
Change in Subject Rating of Breathing Discomfort (Dyspnea) Before and After Treatment.
Subjects will rate breathing discomfort (dyspnea) during a 15 min exercise test using a visual analog scale before and after drug (or placebo) intervention. The treatment effect was measured as the rating of breathing discomfort rating before treatment minus the rating of breathing discomfort after treatment at equivalent work intensities. Outcome Measure Time Frame: subjects performed arm exercise to induce dyspnea for approximately 15 min before and after aerosol inhalation. the average number of minutes between end of drug administration and post-intervention breathing discomfort rating: Aerosol furosemide Study 2a arm: 38.7 minutes; Aerosol furosemide Study 2b arm: 21.8 minutes; Aerosol saline Study 2b arm: 21.3 minutes
Time frame: 15 min
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aerosol Furosemide Study 2a | Change in Subject Rating of Breathing Discomfort (Dyspnea) Before and After Treatment. | -1.86 units on a scale | Standard Deviation 2.31 |
| Aerosol Furosemide Study 2b | Change in Subject Rating of Breathing Discomfort (Dyspnea) Before and After Treatment. | -0.61 units on a scale | Standard Deviation 1.61 |
| Aerosol Saline Study 2b | Change in Subject Rating of Breathing Discomfort (Dyspnea) Before and After Treatment. | -0.15 units on a scale | Standard Deviation 0.94 |
Comparison: This is a paired t-test comparing the treatment effect of furosemide to the treatment effect of saline in each individual.p-value: 0.35t-test, 2 sided
Secondary
Urine Output - mL
Diuresis is an expected effect of furosemide. To the extent that aerosol furosemide is absorbed in the blood, diuresis is an expected 'side effect' of this treatment. Following intervention, study team will measure urine output (mL). Study team will then rehydrate subject with an equal amount of liquid to their output.
Time frame: Summation of total urine output (mL) at 1 hour following drug administration.
Population: The 17 participants in 'Aerosol furosemide Study 2b' and 'Aerosol saline Study 2b' are the results from the same 17 subjects on two different test days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aerosol Furosemide Study 2a | Urine Output - mL | 189.8 ml of urine | Standard Deviation 236.2 |
| Aerosol Furosemide Study 2b | Urine Output - mL | 573.6 ml of urine | Standard Deviation 237.8 |
| Aerosol Saline Study 2b | Urine Output - mL | 63.9 ml of urine | Standard Deviation 93.9 |
p-value: <0.001t-test, 2 sided