PROJECT HIGHLIGHTS
Governance Organization
AMO – Academic Medical Organization of Southwestern Ontario
Project Title
AMO-20-031 – Exogenous Surfactant Administration for Patients with COVID-19: the LESSCOVID trial (the London Exogenous Surfactant Study for COVI19)
Project Highlights
London Exogenous Surfactant Study in COVID-19 Patients (LESSCOVID) Background and Rationale Over the last 30 years, our laboratory has investigated cellular, in vivo and clinical studies focused on the role of the surfactant system in the pathophysiology of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). We have shown that the administration of exogenous surfactant to these critically ill patients improves outcomes (i.e., mortality), particularly in patients with pneumonia or aspiration-induced lung injury (“direct’ lung injuries). The rationale for the current pilot study was based on several factors. First, COVID-19-induced pneumonia in patients requiring mechanical ventilation is similar to ARDS patients with “direct” lung injuries. Secondly, the COVID-19 virus, itself attacks type 2 cells, which are responsible for endogenous surfactant synthesis and secretion. Finally, mechanical ventilation in patients with respiratory failure due to ALI, enhances the progression of this disorder, in part, due to dysfunction of endogenous surfactant. Objective The objective of the current study was to determine the feasibility and safety of administering exogenous surfactant to patients with COVID-19-induced pneumonia requiring mechanical ventilation. Once safety and feasibility is demonstrated in this small pilot study, a larger, randomized multicentered clinical trial would be designed to determine its efficacy on mortality and days alive and free of invasive mechanical ventilation. Mortality is significant in these patients and the requirement for mechanical ventilation exhausts resources; thus, any decrease in mortality or time on a ventilator would be clinically important to patients and the Ontario healthcare system. Experimental Approach (ClinicalTrials.gov Identifier: NCT04375735) We performed a local pilot study involving 20 patients (10 treatment and 10 control patients) with the primary objective of establishing safety and feasibility. The pilot study was based on our local expertise in administering surfactant to critically ill patients (see video) and our ability to access (free of charge), a commercially available natural surfactant preparation made locally in London, Ontario. This surfactant is called Bovine Lipid Extract Surfactant (BLES) (kindly donated by BLES Pharmaceuticals Inc.) and is currently used routinely in infants born prematurely who are deficient in surfactant. After informed consent was obtained, patients were randomly assigned to a treatment group (BLES administered intratracheally via the suction catheter within 48 hours of intubation and given every 24 hours up to 3 doses). Patients in the control group received a sham treatment every 24 hours up to 3 treatments. Acute physiologic responses including oxygenation, lung compliance and hemodynamics were monitored frequently throughout the treatment period as were reports of any adverse events and potential transmission of COVID-19 to health care workers. We recorded the number of days patients were on a ventilator as well vital status at ICU and hospital discharge. Results We enrolled patients from November 11, 2020 to May 6, 2021 during the “second and third waves” of the pandemic. Patients’ ages ranged from 24 to 77 years and included 14 males and 6 females. In terms of feasibility, In most cases, consent was obtained (few declined) and first dose was administered within 48 hours of intubation. Regarding safety, no adverse events were reported related to surfactant administration and ventilator circuit breaches were minimal. There were no reported new cases of COVID-19 in health care workers involved in the treatment or control groups. Acute physiologic responses (oxygenation and lung compliance) were similar between groups as were the number of days on the mechanical ventilator (mean of 18.7 days in the BLES treated group vs. 23.1 days in the control group). Five patients in the treatment group died and 5 patients in the control group died; one patient was lost to follow-up. There were no statistical differences between the two groups. Summary and Future Studies In summary, we showed that recruitment, enrollment and treatment of mechanically ventilated COVID-19 patients in the LESSCOVID Studywas feasible. Although no significant differences in acute physiologic response were detected between treatment and control group, our objective was to confirm feasibility and safety of patients and health care workers. We achieved these objectives, and obtained valuable information to inform the design of a larger, multicentered study involving exogenous surfactant in preparation for future pandemics.
Theme
Prevention and Treatment
Primary Project Lead for Contact
Dr. Jim Lewis
Secondary Project Lead for Contact
Dr. Karen Bosma