Furosemide as Supportive Therapy for COVID-19 Respiratory Failure

Phase 3TerminatedNCT04588792

Dr. John Muscedere40 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Covid19 Respiratory Failure

Interventions

Nebulized FurosemideDRUG

Furosemide administered by nebulization through the ventilator circuit

Nebulized SalineDRUG

Saline administered by nebulization through the ventilator circuit

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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

Locations (4)

University of Alberta

Edmonton, Alberta, Canada

Dalhousie University

Halifax, Nova Scotia, Canada

Kingston Health Sciences Center

Kingston, Ontario, Canada

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Outcomes

Primary Outcomes

Improvement in pulmonary gas exchange

Improvement in oxygenation as determined by a standardized PaO2/FiO2 ratio

Time frame: Study Day 6

Requirement for mechanical ventilation

Number of ventilator-free days in the first 28 days after enrollment

Time frame: Baseline to day 28

Secondary Outcomes

Mortality

All Cause

Time frame: Day 60 post enrollment

Requirement for supplemental oxygen

Number of days of alive and not requiring supplemental oxygen

Time frame: To day 28 post enrollment

Duration of ICU Stay

Time frame: Up to 60 days post enrollment

Length of hospitalization

Time frame: Up to 60 days post enrollment

Adverse events

Incidence of serious adverse events: incorporated as trial outcomes, defined a priori, in accordance with guidelines for academic ICU drug trials

Time frame: Up to 60 days post enrollment

Inhalation adverse events

Adverse events during the nebulization of furosemide

Time frame: Up to day 28

Data from ClinicalTrials.gov

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