London's Exogenous Surfactant Study for COVID19 (LESSCOVID)

Phase I/II Trial: Exogenous Surfactant Administration for Patients With COVID-19

The research team is investigating administering exogenous surfactant in COVID-19 patients with ARDS. The overall goal is to improve the outcome (mortality) of mechanically ventilated COVID-19 patients. Although the investigators anticipate that clinical outcomes may improve in the small group of patients receiving exogenous surfactant therapy in this small, single center study, the primary goal is to first determine feasibility and safety.

Study Overview

• Status: Completed
• Conditions: COVID-19; ARDS, Human
• Intervention / Treatment: Drug: Bovine Lipid Extract Surfactant

Detailed Description

The most severe patients infected by the virus that causes COVID-19 develop severe respiratory failure (called ARDS) and require mechanical ventilation in the intensive care unit to help maintain oxygen delivery to the blood. Often these patients further deteriorate while on mechanical ventilation. This trial will determine the feasibility and safety of a therapy that can potentially improve lung function, reduce the need for mechanical ventilation and hopefully impact mortality.

Adult patients with COVID-19 induced respiratory failure will be randomly assigned to receive either standard treatment or standard treatment plus exogenous surfactant. If enrolled in the latter, exogenous surfactant will be instilled into the lungs within 48 hours of intubation.

The study is founded on extensive research on ARDS for over 30 years, leading to evidence suggesting that exogenous surfactant administration may be beneficial in this disease. Importantly, exogenous surfactant is already utilized all over the world to reduce mortality in preterm infants. When tested in adults with ARDS, it was shown to be well tolerated and safe. Furthermore, clinical and laboratory evidence suggests that this therapy may be most effective in patients with a direct lung infection, and when administered shortly after the patient is intubated. In this study, twenty patients who are proven COVID-19 positive and require MV due to progressive respiratory failure will be randomized to receive either 1) exogenous surfactant (BLES) as soon as possible and within 48 hours of intubation and stabilization, or 2) treatment as usual (will not be treated with surfactant). The overall goal is to improve the outcome (mortality) of mechanically ventilated COVID-19 patients. Although the investigators anticipate that clinical outcomes may improve in the small group of patients receiving exogenous surfactant therapy in this small, single center study, the primary goal is to first determine feasibility and safety. Should the investigators obtain promising results, the data obtained from this study will be used to develop a large trial to test the impact of this therapy on the clinical outcomes, including mortality, associated with COVID-19.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre - University Hospital
    • London, Ontario, Canada
      • Victoria Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. age over 18 years
2. definitive proof of COVID-19 infection within 48 hours of intubation
3. acute respiratory failure with PaO2/FiO2 < 300 requiring intubation

Exclusion Criteria:

1. known or high suspicion of pre-existing heart failure, unstable angina
2. presence of severe shock with hemodynamic instability despite escalating vasopressors
3. severe, underlying lung disease (COPD, pulmonary fibrosis, lung cancer. etc.)
4. Concurrent treatments are delivered directly into the lung (ie anesthetics etc)
5. Diagnosis of pulmonary hemorrhage

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BLES treatment; For patients randomized to the treatment arm, exogenous BLES will be administered as soon as possible and within 48 hours of intubation. BLES will be administered daily for up to 3 doses, or until the patient is liberated from the ventilator.	Drug: Bovine Lipid Extract Surfactant; BLES will be administered in doses of 50mg/kg ideal bodyweight, at a concentration of 27mg/ml so a total volume of approximately 2ml/kg will be administered. The material will be instilled via the suction catheter through the ET tube so that the ventilation circuit is not broken. Half of the material will be instilled with the patient positioned on their left and right sides, with a pause to allow 5 min of MV between. The procedure will be repeated at, 24 and 48 hours while intubated, so the patient will receive up to 3 doses. To minimize aerosol generation, all patients will be paralyzed during surfactant administration and the ventilator will be paused. The proposed administration technique, surfactant concentration, volume and dosing schedule is based on previous studies, and has shown to be safe in patients with ARDS.; Other Names: BLES; Lung Surfactant; Bovine
No Intervention: Control; Patients will receive standard treatment and will not receive surfactant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (patient) - Decrease in oxygenation	Count of any decreases in oxygenation, expressed as PaO2 (mmHg) / FiO2 (% oxygen as a decimal), of greater than 20% during the BLES treatment and up to 30 minutes post-treatment. Change will be calculated relative to pre-treatment values.	3 days post-randomization
Adverse events (patient) - Decrease in hemodynamics	Count of any decrease in mean arterial blood pressure >10 mmHg or requirement for >20% increase in vasopressor dose during the BLES procedure and up to 30 minutes post-treatment. Change will be calculated relative to the pre-treatment values.	3 days post-randomization
Adverse event (healthcare worker) - Circuit breach	Number of circuit breaches. Count of any circuit breach immediately prior to and during each BLES treatment procedure will be recorded.	3 days post-randomization
Adverse event (healthcare worker) - COVID-19 symptoms	Count of healthcare personnel involved in the BLES procedure developing symptoms and testing positive for COVID-19.	2 weeks post-randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in oxygenation	PaO2 (in mmHg) / FiO2 (percentage oxygen expressed as a decimal) ratios captured from clinical chart	Every 12 hours post-randomization until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days.
Change in Lung compliance	Lung compliance captured from the ventilators, expressed in mL/cm H2O.	Every 12 hours post-randomization until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days.
Ventilated days	The number of days the patient is receiving mechanical ventilation.	From ICU admission until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days
Length of ICU stay	The number of days the patient is admitted to the ICU	From ICU admission until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days
Length of hospital stay	The number of days the patient is admitted to the hospital	From hospital admission until hospital discharge or death, whichever comes first, assessed up to 60 days
Mortality	Number of patients who die within 30 days of ICU admission	30 days
G-CSF levels (serum inflammatory biomarker)	G-CSF, in pg/mL, from multiplex cytokine arrays	ICU day 0, 1, 3 and 7 (7 days)
GM-CSF levels (serum inflammatory biomarker)	GM-CSF, in pg/mL, from multiplex cytokine arrays	ICU day 0, 1, 3 and 7 (7 days)
IFN gamma levels (serum inflammatory biomarker)	IFN gamma, in pg/mL, from multiplex cytokine arrays	ICU day 0, 1, 3 and 7 (7 days)
IL-1 beta levels (serum inflammatory biomarker)	IL-1 beta, in pg/mL, from multiplex cytokine arrays	ICU day 0, 1, 3 and 7 (7 days)
IL-4 levels (serum inflammatory biomarker)	IL-4, in pg/mL, from multiplex cytokine arrays	ICU day 0, 1, 3 and 7 (7 days)
IL-6 levels (serum inflammatory biomarker)	IL-6, in pg/mL, from multiplex cytokine arrays	ICU day 0, 1, 3 and 7 (7 days)
IL-10 levels (serum inflammatory biomarker)	IL-10, in pg/mL, from multiplex cytokine arrays	ICU day 0, 1, 3 and 7 (7 days)
I levels (serum inflammatory biomarker)	I, in pg/mL, from multiplex cytokine arrays	ICU day 0, 1, 3 and 7 (7 days)
MCP-1 levels (serum inflammatory biomarker)	MCP-1, in pg/mL, from multiplex cytokine arrays	ICU day 0, 1, 3 and 7 (7 days)
TNF alpha levels (serum inflammatory biomarker)	TNF alpha, in pg/mL, from multiplex cytokine arrays	ICU day 0, 1, 3 and 7 (7 days)

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Collaborators: London Health Sciences Centre
• Investigators: Principal Investigator: Jim Lewis, MD, Lawson Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2020
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): October 6, 2021

Study Registration Dates

• First Submitted: April 22, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 5, 2020

Study Record Updates

• Last Update Posted (Actual): November 11, 2021
• Last Update Submitted That Met QC Criteria: November 4, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Respiratory Distress Syndrome; Respiratory System Agents; Pulmonary Surfactants
• Other Study ID Numbers: 9890

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No