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Furosemide as Supportive Therapy for COVID-19 Respiratory Failure (FaST-1)

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ClinicalTrials.gov Identifier: NCT04588792
Recruitment Status : Recruiting
First Posted : October 19, 2020
Last Update Posted : April 21, 2021
Sponsor:
Collaborator:
University Health Network, Toronto
Information provided by (Responsible Party):
Dr. John Muscedere, Queen's University

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.

Condition or disease Intervention/treatment Phase
Covid19 Respiratory Failure Drug: Nebulized Furosemide Drug: Nebulized Saline Phase 2 Phase 3

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 640 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19 - A Phase 2/3 Study
Actual Study Start Date : April 16, 2021
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : March 1, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Furosemide

Arm Intervention/treatment
Experimental: Inhaled 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
Drug: Nebulized Furosemide
Furosemide administered by nebulization through the ventilator circuit

Placebo Comparator: 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
Drug: Nebulized Saline
Saline administered by nebulization through the ventilator circuit




Primary Outcome Measures :
  1. Improvement in pulmonary gas exchange [ Time Frame: Study Day 6 ]
    Improvement in oxygenation as determined by a standardized PaO2/FiO2 ratio

  2. Requirement for mechanical ventilation [ Time Frame: Baseline to day 28 ]
    Number of ventilator-free days in the first 28 days after enrollment


Secondary Outcome Measures :
  1. Mortality [ Time Frame: Day 60 post enrollment ]
    All Cause

  2. Requirement for supplemental oxygen [ Time Frame: To day 28 post enrollment ]
    Number of days of alive and not requiring supplemental oxygen

  3. Duration of ICU Stay [ Time Frame: Up to 60 days post enrollment ]
    Duration of ICU Stay

  4. Length of hospitalization [ Time Frame: Up to 60 days post enrollment ]
    Length of hospitalization

  5. Adverse events [ Time Frame: 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

  6. Inhalation adverse events [ Time Frame: Up to day 28 ]
    Adverse events during the nebulization of furosemide


Other Outcome Measures:
  1. Serum levels of furosemide [ Time Frame: Up to day 28 ]
    Serum levels of furosemide every 7 days until the completion of therapy

  2. Electrolyte abnormalities [ Time Frame: Up to day 28 ]
    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

  3. Cytokine levels [ Time Frame: Up to day 28 ]
    Levels of serum inflammatory cytokines (IL-6, IL-8, TNF-α) at baseline prior to first dose of intervention, day 7, and the completion of therapy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04588792


Contacts
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Contact: John Muscedere, MD 6135496666 ext 4642 John.Muscedere@kingstonhsc.ca
Contact: Tracy Boyd 6135496666 Tracy.Boyd@kingstonhsc.ca

Locations
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Canada, Alberta
University of Alberta Not yet recruiting
Edmonton, Alberta, Canada
Contact: Oleksa Rewa, MD       rewa@ualberta.ca   
Canada, Nova Scotia
Dalhousie University Not yet recruiting
Halifax, Nova Scotia, Canada
Contact: Osama Loubani, MD       oloubani@dal.ca   
Canada, Ontario
Kingston Health Sciences Center Recruiting
Kingston, Ontario, Canada, K7L2V7
Contact: John Muscedere, MD    6135496666 ext 4642    John.Muscedere@kingstonhsc.ca   
Sub-Investigator: Gordon Boyd, MD         
Sub-Investigator: Dave Maslove, MD         
Principal Investigator: Stephanie Sibley, MD         
Canada, Quebec
Hôpital Maisonneuve-Rosemont Not yet recruiting
Montréal, Quebec, Canada
Contact: HT Wand, MD       ht.wang85@gmail.com   
Sponsors and Collaborators
Queen's University
University Health Network, Toronto
Investigators
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Principal Investigator: John Muscedere, MD Queens University
Publications:
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Responsible Party: Dr. John Muscedere, Professor of Medicine, Queen's University, Queen's University
ClinicalTrials.gov Identifier: NCT04588792    
Other Study ID Numbers: FaST-1
First Posted: October 19, 2020    Key Record Dates
Last Update Posted: April 21, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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COVID-19
Respiratory Insufficiency
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Furosemide
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action