Aerosol Inhalation Treatment for Dyspnea - Patients

Aerosol Inhalation Treatment for Dyspnea

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.

Study Overview

• Status: Completed
• Conditions: Dyspnea
• Intervention / Treatment: Drug: Furosemide; Drug: Aerosolized saline

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Furosemide; 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.; Other Names: Lasix
Experimental: Aerosol furosemide Study 2b Arm F; 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; 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.; Other Names: Lasix; Drug: Aerosolized 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.; Other Names: Placebo
Experimental: Aerosol furosemide Study 2b Arm S; 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; 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.; Other Names: Lasix; Drug: Aerosolized 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.; Other Names: Placebo

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: National Institute of Nursing Research (NINR)
• Investigators: Principal Investigator: Robert Banzett, PhD, Beth Israel Deaconess Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): November 30, 2016
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: May 5, 2015
• First Submitted That Met QC Criteria: August 13, 2015
• First Posted (Estimate): August 14, 2015

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: December 21, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Chronic obstructive pulmonary disease; Dyspnea; Shortness of breath; Pulmonary disease; Hospitalized patients; Ambulatory outpatients
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Dyspnea; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: 2011P000027; R01NR012009 (U.S. NIH Grant/Contract)