Aerosol Inhalation Treatment for Dyspnea - Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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Aerosol Inhalation Treatment for Dyspnea

Conditions
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Dyspnea

Intervention / Treatment
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* Drug: Furosemide
* Drug: Aerosolized saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerosol furosemide Study 2a<br>Subjects will inhale 40mg of furosemide aerosol over the course of 10-15 min. This will be a single, unblinded administration. | Drug: Furosemide<br>* 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.<br>* Other names: Lasix;|
| Experimental: Aerosol furosemide Study 2b Arm F<br>Inhalation of furosemide aerosol one one day then placebo saline aerosol on another day. Baseline measurement 15 min; Inhalation over the course of 10-15 min.; outcome measurement 15 min. Watch for adverse effects 2 hours. | Drug: Furosemide<br>* 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.<br>* Other names: Lasix;Drug: Aerosolized saline<br>* 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.<br>* Other names: Placebo;|
| Experimental: Aerosol furosemide Study 2b Arm S<br>Inhalation of saline aerosol one one day then furosemide aerosol on another day. Baseline measurement 15 min; Inhalation over the course of 10-15 min.; outcome measurement 15 min. Watch for adverse effects 2 hours. | Drug: Furosemide<br>* 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.<br>* Other names: Lasix;Drug: Aerosolized saline<br>* 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.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 15 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Summation of total urine output (mL) at 1 hour following drug administration. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dyspnea, Hospitalized patients, Ambulatory outpatients, Shortness of breath, Chronic obstructive pulmonary disease, Pulmonary disease