Furosemide as Supportive Therapy for COVID-19 Respiratory Failure

Covid19 Clinical Trial

— FaST-1  

Official title:

Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19 - A Phase 2/3 Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04588792
• Other study ID #: FaST-1
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: April 16, 2021
• Est. completion date: April 30, 2023

Study information

• Verified date: December 2023
• Source: Queen's University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: April 30, 2023
• Est. primary completion date: February 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Respiratory Failure
• Respiratory Insufficiency

Intervention

Drug:
• Nebulized Furosemide
Furosemide administered by nebulization through the ventilator circuit
• Nebulized Saline
Saline administered by nebulization through the ventilator circuit

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta
Canada	Dalhousie University	Halifax	Nova Scotia
Canada	Kingston Health Sciences Center	Kingston	Ontario
Canada	Hôpital Maisonneuve-Rosemont	Montréal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Dr. John Muscedere	University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum levels of furosemide	Serum levels of furosemide every 7 days until the completion of therapy	Up to day 28
Other	Electrolyte abnormalities	Altered electrolytes on routine testing (frequency of hypokalemia (< 3.0 meq/L), hypernatremia (> 150 meq/L) or increased bicarbonate levels (>30 meq/L) during the ICU stay	Up to day 28
Other	Cytokine levels	Levels of serum inflammatory cytokines (IL-6, IL-8, TNF-a) at baseline prior to first dose of intervention, day 7, and the completion of therapy	Up to day 28
Primary	Improvement in pulmonary gas exchange	Improvement in oxygenation as determined by a standardized PaO2/FiO2 ratio	Study Day 6
Primary	Requirement for mechanical ventilation	Number of ventilator-free days in the first 28 days after enrollment	Baseline to day 28
Secondary	Mortality	All Cause	Day 60 post enrollment
Secondary	Requirement for supplemental oxygen	Number of days of alive and not requiring supplemental oxygen	To day 28 post enrollment
Secondary	Duration of ICU Stay	Duration of ICU Stay	Up to 60 days post enrollment
Secondary	Length of hospitalization	Length of hospitalization	Up to 60 days post enrollment
Secondary	Adverse events	Incidence of serious adverse events: incorporated as trial outcomes, defined a priori, in accordance with guidelines for academic ICU drug trials	Up to 60 days post enrollment
Secondary	Inhalation adverse events	Adverse events during the nebulization of furosemide	Up to day 28