The Impact of Inhaled Furosemide and Perorally Administered Levodropropizine on Dyspnea in Patients With Respiratory Diseases (INFURO)

The goal of this monocentric double blinded cross over trial is to evaluate safety and tolerability of inhaled furosemide in patients with pulmonary diseases and dyspnea.

The main question[s] it aims to answer are:

• is inhaled furosemide safe and well tolerated?
• is inhaled furosemide capable of dyspnea suppression and is there any additive effect of levodropropizine

Participants will be given:

• inhaled furosemide or placebo in double blinded cross over manner. Dyspnea severity and vital functions will be measured, adverse reactions monitored
• all participants will receive levodropropizine open label. Dyspnea severity and vital functions will be measured, adverse reactions monitored

Study Overview

• Status: Recruiting
• Conditions: Dyspnea
• Intervention / Treatment: Drug: Furosemide 40 mg; Drug: Levodropropizine; Other: Placebo - saline

Detailed Description

102 subjects from the pool of patients hospitalized in our pulmonary clinics will be randomized in 1:1 ratio to 2 arms in double blinded manner. Subjects in both arms will inhale first vial of study medication - furosemide 40 mg or placebo (saline). Dyspnea severity and vital functions will be measured, adverse reactions will be monitored. After an hour the subjects will inhale the second vial of study medication followed by the same procedure as earlier. Neither subjects, nor investigators will know which vial contains furosemide and which contains placebo. At last all subjects will receive levodropropizine open label and the dyspnea severity, vital signs and adverse reaction will be monitored for another hour. The measured values will be statistically evaluated a results published.

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Michal Svarc, MD; Phone Number: +420 495 834 771; Email: michal.svarc@fnhk.cz
• Study Contact Backup: Name: Vladimir Koblizek, PhD; Phone Number: +420 495 834 771; Email: vladimir.koblizek@fnhk.cz

Study Locations

• Czechia
  • Hradec Králové, Czechia, 50005
    • Recruiting
    • Plicní klinika, Fakultni nemocnice Hradec Kralove
    • Contact: Vladimír Koblížek, Doc., PhD; Phone Number: +420495834771; Email: vladimir.koblizek@fnhk.cz
    • Principal Investigator: Vladimír Koblížek, Doc, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ability to understand and sing written consent
• ability to use visual analogue (VAS) and Borg dyspnea scale
• presence of lung disease (asthma, chronic obstructive pulmonary disease, interstitial pulmonary disease, tumour affecting lungs, Coronavirus Disease 2019 (COVID19), drug induced dyspnea, lung infection)
• dyspnea at least 50 points in VAS and at least 5 point in Borg dyspnea scale
• women of childbearing age consent ot avoid sexual intercourse during the study participation

Exclusion Criteria:

• hypersensitivity to furosemide, levodropropizine or any additives in studied drugs
• mucociliary disorder (kartegener syndrome, ciliary dyskinesis)
• severe liver disease - cirrhosis Child Pugh B or C
• renal failure, creatinine clearance less than 35 ml/min
• unstable patient requiring frequent treatment changes
• patients with continual intravenous medication requiring modification of their therapy more often than ever 4 hours
• unability to participate in all study procedures
• pregnancy, breast feeding
• participation in other clinical trial with administration of study drug in last 28 days or 5 half times of studied drug (the longer period is taken into account) before screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Furosemide; Subjects will inhale once 40 mg of furosemide for 23 minutes, next they will be monitored for an hour and then cross over will take place, the subjects will inhale placebo - saline for 23 minutes and another hour of monitoring and observation will take place. Lastly all subject will be given levodropropizine 1 ml (60mg) with last hour of monitoring and observation	Drug: Furosemide 40 mg; Furosemide will be used to block C fibers in the lungs, thus lowering intensity of sensation of dyspnea.; Drug: Levodropropizine; Levodropropizine will be used to block C fibers in the airways, to evaluate if this double block of C fibers will have any effect on lowering intensity of dyspnea sensation; Other Names: Levopront
Placebo Comparator: Placebo; Subjects will inhale once placebo - saline for 23 minutes, next they will be monitored for an hour and then cross over will take place, the subjects will inhale 40 mg of furosemide for 23 minutes and another hour of monitoring and observation will take place. Lastly all subject will be given levodropropizine 1 ml (60mg) with last hour of monitoring and observation	Drug: Levodropropizine; Levodropropizine will be used to block C fibers in the airways, to evaluate if this double block of C fibers will have any effect on lowering intensity of dyspnea sensation; Other Names: Levopront; Other: Placebo - saline; Placebo will be used as a comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of inhaled furosemide	Incidence of Treatment-Emergent Adverse Events (AE) will be measured and reported. Any deterioration of clinical status of the subject during the study procedure will be reported as AE, especially but not only bronchospasm, worsening of the dyspnea, hemodynamic deterioration and every other event requiring change of the treatment of the subject during the study procedures and within next 24 hours until follow up visit.	24 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To prove abilty of inhaled furosemide to alleviate dyspnea	Dyspnea severity will be measured using Visual Analogue Scale (range 0 - 100 meaning 0 no dyspnea at all, 100 worst dyspnea imaginable) before and one hour after each inhalation (furosemide, placebo) calculating the change of dyspnea severity on the scale (decrease of the value on scale meaning improvement of dyspnea)	226 minutes
To prove abilty of inhaled furosemide to alleviate dyspnea	Dyspnea severity will be measured using Borg dyspnea scale (range 0-10, meaning 0 no dyspnea at all, 10 worst dyspnea imaginable) before and one hour after each inhalation (furosemide, placebo) calculating the change of dyspnea severity on the scale (decrease of the value on scale meaning improvement of dyspnea)	226 minutes
To discover any additive effect of levodropropizine to alleviate dyspnea	Dyspnea severity will be measured using Visual Analogue Scale (range 0 - 100 meaning 0 no dyspnea at all, 100 worst dyspnea imaginable) the change of dyspnea severity on the scale will be calculated after adding levodropropizine (decrease of the value on scale meaning improvement of dyspnea)	226 minutes whole study, 60 minutes levodropropizine intervention
To discover any additive effect of levodropropizine to alleviate dyspnea	Dyspnea severity will be measured using Borg dyspnea scale (range 0-10, meaning 0 no dyspnea at all, 10 worst dyspnea imaginable) the change of dyspnea severity on the scale will be calculated after adding levodropropizine (decrease of the value on scale meaning improvement of dyspnea)	226 minutes whole study, 60 minutes levodropropizine intervention

Collaborators and Investigators

• Sponsor: University Hospital Hradec Kralove
• Collaborators: Masaryk University
• Investigators: Principal Investigator: Vladimir Koblizek, PhD, head of department

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2024
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 2, 2024
• First Submitted That Met QC Criteria: February 7, 2024
• First Posted (Actual): February 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Respiration Disorders; Respiratory Tract Diseases; Dyspnea; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Respiratory System Agents; Antitussive Agents; Sodium Potassium Chloride Symporter Inhibitors; Furosemide; Dipropizine
• Other Study ID Numbers: INFURO_2023; 2018-001298-26 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No