Furosemide as Supportive Therapy for COVID-19 Respiratory Failure

Phase 2

Terminated

• Conditions: Respiratory Failure; Covid19
• Interventions: Drug: Nebulized Saline; Drug: Nebulized Furosemide

• Registration Number: NCT04588792
• Lead Sponsor: Dr. John Muscedere

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).

Study Timeline

• Study First Submitted: 2020-10-14
• Study First Submitted QC: 2020-10-14
• Study First Posted: 2020-10-19
• Study Start: 2021-04-16
• Primary Completion: 2023-02-01
• Study Completion: 2023-04-30
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-04
• Last Update Posted: 2023-12-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nebulized Saline	Nebulized Saline	Placebo, given by nebulization (4 mL of 0.9% saline solution) over 30 mins four times daily (Q.I.D.) for up to 28 days
Inhaled Furosemide	Nebulized Furosemide	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

Primary Outcome Measures

Name	Time	Method
Improvement in pulmonary gas exchange	Study Day 6	Improvement in oxygenation as determined by a standardized PaO2/FiO2 ratio
Requirement for mechanical ventilation	Baseline to day 28	Number of ventilator-free days in the first 28 days after enrollment

Secondary Outcome Measures

Name	Time	Method
Mortality	Day 60 post enrollment	All Cause
Requirement for supplemental oxygen	To day 28 post enrollment	Number of days of alive and not requiring supplemental oxygen
Duration of ICU Stay	Up to 60 days post enrollment	Duration of ICU Stay
Length of hospitalization	Up to 60 days post enrollment	Length of hospitalization
Inhalation adverse events	Up to day 28	Adverse events during the nebulization of furosemide
Adverse events	Up to 60 days post enrollment	Incidence of serious adverse events: incorporated as trial outcomes, defined a priori, in accordance with guidelines for academic ICU drug trials

Trial Locations

Locations (4)

Dalhousie University; 🇨🇦 Halifax, Nova Scotia, Canada

Kingston Health Sciences Center; 🇨🇦 Kingston, Ontario, Canada

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Hôpital Maisonneuve-Rosemont; 🇨🇦 Montréal, Quebec, Canada