Nebulised surfactant for the treatment of severe COVID-19 in adults (COV-Surf): A structured summary of a study protocol for a randomized controlled trial

SARS-Cov-2 virus preferentially binds to the Angiotensin Converting Enzyme 2 (ACE2) on alveolar epithelial type II cells, initiating an inflammatory response and tissue damage which may impair surfactant synthesis contributing to alveolar collapse, worsening hypoxia and leading to respiratory failur...

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Published in:	Current controlled trials in cardiovascular medicine 2020-12, Vol.21 (1), p.1014-3, Article 1014
Main Authors:	Dushianthan, Ahilanandan, Clark, Howard, Madsen, Jens, Mogg, Robin, Matthews, Lewis, Berry, Lee, de la Serna, Jorge Bernardino, Batchelor, James, Brealey, David, Hussell, Tracy, Porter, Joanna, Djukanovic, Ratko, Feelisch, Martin, Postle, Anthony, Grocott, Michael P W
Format:	Article
Language:	eng
Subjects:	Adult Case-Control Studies Coronaviruses COVID-19 COVID-19 - drug therapy COVID-19 - epidemiology COVID-19 - mortality COVID-19 - virology Drug dosages Feasibility Studies Humans Intensive Care Intensive Care Units - statistics & numerical data Letter London - epidemiology mechanical ventilation Mortality - trends Nebulizers and vaporizers Nebulizers and Vaporizers - standards Nebulizers and Vaporizers - statistics & numerical data protocol Randomised controlled trial Respiration, Artificial - methods Respiratory Insufficiency - metabolism Respiratory Insufficiency - physiopathology Respiratory Insufficiency - therapy Safety SARS-CoV-2 - genetics Severe acute respiratory syndrome coronavirus 2 Surface active agents Surface-Active Agents - administration & dosage Surface-Active Agents - chemistry Surface-Active Agents - therapeutic use surfactant Surfactants Testing Treatment Outcome Ventilation - statistics & numerical data Ventilators
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Summary:	SARS-Cov-2 virus preferentially binds to the Angiotensin Converting Enzyme 2 (ACE2) on alveolar epithelial type II cells, initiating an inflammatory response and tissue damage which may impair surfactant synthesis contributing to alveolar collapse, worsening hypoxia and leading to respiratory failure. The objective of this study is to evaluate the feasibility, safety and efficacy of nebulised surfactant in COVID-19 adult patients requiring mechanical ventilation for respiratory failure. This study is a dose-escalating randomized open-label clinical trial of 20 COVID-19 patients. This study is conducted in two centres: University Hospital Southampton and University College London Hospitals. Eligible participants are aged ≥18, hospitalised with COVID-19 (confirmed by PCR), who require endotracheal intubation and are enrolled within 24 hours of mechanical ventilation. For patients unable to consent, assent is obtained from a personal legal representative (PerLR) or professional legal representative (ProfLR) prior to enrolment. The following are exclusion criteria: imminent expected death within 24 hours; specific contraindications to surfactant administration (e.g. known allergy, pneumothorax, pulmonary hemorrhage); known or suspected pregnancy; stage 4 chronic kidney disease or requiring dialysis (i.e., eGFR < 30); liver failure (Child-Pugh Class C); anticipated transfer to another hospital, which is not a study site, within 72 hours; current or recent (within 1 month) participation in another study that, in the opinion of the investigator, would prevent enrollment for safety reasons; and declined consent or assent. Intervention: The study is based on an investigational drug/device combination product. The surfactant product is Bovactant (Alveofact®), a natural animal derived (bovine) lung surfactant formulated as a lyophilized powder in 108 mg vials and reconstituted to 45 mg/mL in buffer supplied in a prefilled syringe. It is isolated by lung lavage and, by weight, is a mixture of: phospholipid (75% phosphatidylcholine, 13% phosphatidylglycerol, 3% phosphatidylethanolamine, 1% phosphatidylinositol and 1% sphingomyelin), 5% cholesterol, 1% lipid-soluble surfactant-associated proteins (SP-B and SP-C), very low levels of free fatty acid, lyso-phosphatidylcholine, water and 0.3% calcium. The Drug Delivery Device is the AeroFact-COVID™ nebulizer, an investigational device based on the Aerogen® Solo vibrating mesh nebulizer. The timing and escalation dosing plan
ISSN:	1745-6215 1745-6215 1468-6694