Furosemide as Supportive Therapy for COVID-19 Respiratory Failure

NCT ID: NCT04588792

Last Updated: 2023-12-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-16
• Study Completion Date: 2023-04-30

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).

Conditions

Covid19; Respiratory Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Nebulized Furosemide

Intervention Type: DRUG

Furosemide administered by nebulization through the ventilator circuit

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

Group Type: PLACEBO_COMPARATOR

Nebulized Saline

Intervention Type: DRUG

Saline administered by nebulization through the ventilator circuit

Interventions

Nebulized Furosemide

Furosemide administered by nebulization through the ventilator circuit

Intervention Type: DRUG

Nebulized Saline

Saline administered by nebulization through the ventilator circuit

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: collaborator

Dr. John Muscedere

OTHER

Sponsor Role: lead

Responsible Party

Dr. John Muscedere

Professor of Medicine, Queen's University

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

John Muscedere, MD

Role: PRINCIPAL_INVESTIGATOR

Queens University

Locations

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

Countries

Canada

References

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.

Reference Type: BACKGROUND

PMID: 32622469 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32704455 (View on PubMed)

Other Identifiers

FaST-1

Identifier Type: -

Identifier Source: org_study_id