Clinical trial NCT04375735: London's Exogenous Surfactant Study for COVID19
Official title: Phase I/II Trial: Exogenous Surfactant Administration for Patients With COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: ARDS, Human
COVID-19
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: London Health Sciences Centre
First posted: 2020-05-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomly assigned to either receive exogenous surfactant daily for 3 days, or receive standard treatment.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse events (patient) - Decrease in oxygenation
timeFrame: 3 days post-randomization
measure: Adverse events (patient) - Decrease in hemodynamics
timeFrame: 3 days post-randomization
measure: Adverse event (healthcare worker) - Circuit breach
timeFrame: 3 days post-randomization
measure: Adverse event (healthcare worker) - COVID-19 symptoms
timeFrame: 2 weeks post-randomization
Secondary outcomes:
measure: Change in oxygenation
timeFrame: Every 12 hours post-randomization until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days.
measure: Change in Lung compliance
timeFrame: Every 12 hours post-randomization until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days.
measure: Ventilated days
timeFrame: From ICU admission until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days
measure: Length of ICU stay
timeFrame: From ICU admission until ICU discharge or death, whichever comes first, an average of 10 days and assessed up to 30 days
measure: Length of hospital stay
timeFrame: From hospital admission until hospital discharge or death, whichever comes first, assessed up to 60 days
measure: Mortality
timeFrame: 30 days
measure: G-CSF levels (serum inflammatory biomarker)
timeFrame: ICU day 0, 1, 3 and 7 (7 days)
measure: GM-CSF levels (serum inflammatory biomarker)
timeFrame: ICU day 0, 1, 3 and 7 (7 days)
measure: IFN gamma levels (serum inflammatory biomarker)
timeFrame: ICU day 0, 1, 3 and 7 (7 days)
measure: IL-1 beta levels (serum inflammatory biomarker)
timeFrame: ICU day 0, 1, 3 and 7 (7 days)
measure: IL-4 levels (serum inflammatory biomarker)
timeFrame: ICU day 0, 1, 3 and 7 (7 days)
measure: IL-6 levels (serum inflammatory biomarker)
timeFrame: ICU day 0, 1, 3 and 7 (7 days)
measure: IL-10 levels (serum inflammatory biomarker)
timeFrame: ICU day 0, 1, 3 and 7 (7 days)
measure: I levels (serum inflammatory biomarker)
timeFrame: ICU day 0, 1, 3 and 7 (7 days)
measure: MCP-1 levels (serum inflammatory biomarker)
timeFrame: ICU day 0, 1, 3 and 7 (7 days)
measure: TNF alpha levels (serum inflammatory biomarker)
timeFrame: ICU day 0, 1, 3 and 7 (7 days)
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Centre - University Hospital
state: Ontario
city: London
country: Canada
facility: Victoria Hospital
state: Ontario
Study officials:
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Jim Lewis, MD
role: PRINCIPAL_INVESTIGATOR
References: