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.
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).
Drug: Nebulized Furosemide
Furosemide administered by nebulization through the ventilator circuit
Drug: Nebulized Saline
Saline administered by nebulization through the ventilator circuit
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
University of Alberta
Edmonton, Alberta, Canada
Dalhousie University
Halifax, Nova Scotia, Canada
Kingston Health Sciences Center
Kingston, Ontario, Canada
Hôpital Maisonneuve-Rosemont
Montréal, Quebec, Canada
John Muscedere, MD, Principal Investigator
Queens University