Clinical trial NCT04588792: Furosemide as Supportive Therapy for COVID-19 Respiratory Failure
Official title: Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19 - A Phase 2/3 Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Covid19
Respiratory Failure
Lead sponsor: Queen's University
Sponsor class: OTHER
Collaborators: name: University Health Network, Toronto
First posted: 2020-10-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This double-blind, placebo-controlled, randomized, parallel-group phase 2/3 study will study the utility of nebulized furosemide for pulmonary inflammation in Intubated, mechanically ventilated Patients with COVID-19.

Detailed description: This double-blind, placebo-controlled, randomized, parallel-group phase 2/3 study will study the utility of nebulized furosemide for pulmonary inflammation in Intubated, mechanically ventilated Patients with COVID-19. The primary objective of the study is to establish the efficacy and safety of nebulized furosemide for the treatment of respiratory failure secondary to COVID-19 infection requiring invasive mechanical ventilation. The secondary objective is to delineate the anti-inflammatory properties of furosemide in COVID- 19 patients using pharmacokinetic / pharmacodynamic analysis. The duration of the intervention will be up to 28 days of intervention and patients will be followed till 60 days post randomization. Participants will be randomized to either: Intervention Group: 40 mg furosemide per dose, given by nebulization (4 mL of 10 mg/mL furosemide in 0.9% saline solution) over 30 mins four times daily (Q6H) for up to 28 days OR Control Group: placebo, given by nebulization (4 mL of 0.9% saline solution) over 30 mins four times daily for up to 28 days. One hundred and forty-four (144) evaluable patients will be enrolled in the Phase 2 study. If evidence of efficacy is found in the Phase 2 portion, these patients will be enrolled in the Phase 3 study which aims to recruit 640 patients total (496 additional patients to the phase 2 patients).

Eligibility criteria: Inclusion Criteria:

1. Subjects with respiratory failure secondary to COVID-19 (SARS-CoV-2) infection/pneumonia requiring invasive mechanical ventilation
2. Duration of mechanical ventilation less than 48 hours as measured from the time of randomization
3. If female, must not be pregnant at the time of enrollment as determined by a serum or urine pregnancy test

Exclusion Criteria:

1. Known history of severe chronic pulmonary disease (e.g., preinfection requirement for home oxygen therapy or presence of chronic hypercapnia (PaCO2\< 50 mm Hg); mild -moderate disease is still eligible in the absence of chronic hypercapnia or need for chronic oxygen therapy)
2. In the opinion of the PI, unlikely to survive for \>48 hours from time of enrollment
3. Enrollment in another trial of anti-inflammatory therapies for COVID-19.
4. Known allergy to furosemide or sulfonamide agents

Primary outcomes:
measure: Improvement in pulmonary gas exchange
timeFrame: Study Day 6
measure: Requirement for mechanical ventilation
timeFrame: Baseline to day 28
Secondary outcomes:
measure: Mortality
timeFrame: Day 60 post enrollment
measure: Requirement for supplemental oxygen
timeFrame: To day 28 post enrollment
measure: Duration of ICU Stay
timeFrame: Up to 60 days post enrollment
measure: Length of hospitalization
timeFrame: Up to 60 days post enrollment
measure: Adverse events
timeFrame: Up to 60 days post enrollment
measure: Inhalation adverse events
timeFrame: Up to day 28
Other outcomes:
measure: Serum levels of furosemide
timeFrame: Up to day 28
measure: Electrolyte abnormalities
timeFrame: Up to day 28
measure: Cytokine levels
timeFrame: Up to day 28
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Halifax
country: Canada
facility: Dalhousie University
state: Nova Scotia
city: Kingston
country: Canada
facility: Kingston Health Sciences Center
state: Ontario
city: Montréal
country: Canada
facility: Hôpital Maisonneuve-Rosemont
state: Quebec
Study officials:
affiliation: Queens University
name: John Muscedere, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brennecke A, Villar L, Wang Z, Doyle LM, Meek A, Reed M, Barden C, Weaver DF. Is Inhaled Furosemide a Potential Therapeutic for COVID-19? Am J Med Sci. 2020 Sep;360(3):216-221. doi: 10.1016/j.amjms.2020.05.044. Epub 2020 Jun 1.
citation: Wang Z, Wang Y, Vilekar P, Yang SP, Gupta M, Oh MI, Meek A, Doyle L, Villar L, Brennecke A, Liyanage I, Reed M, Barden C, Weaver DF. Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide. PeerJ. 2020 Jul 7;8:e9533. doi: 10.7717/peerj.9533. eCollection 2020.