Annexin A5 in Patients With Severe COVID-19 Disease: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Feasibility Trial

Claudio M. Martin, MD; Marat Slessarev, MD, PhD; Eileen Campbell; John Basmaji, MD; Ian Ball, MD; Douglas D. Fraser, MD, PhD; Aleksandra Leligdowicz, MD, PhD; Tina Mele, MD, PhD; Fran Priestap, MSc; Brent J. Tschirhart, MSc; Tracey Bentall, RN; Xiangru Lu, MD; Qingping Feng, MD, PhD

doi:10.1097/CCE.0000000000000986

Critical Care Explorations (Oct 2023)

Annexin A5 in Patients With Severe COVID-19 Disease: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Feasibility Trial

Claudio M. Martin, MD,
Marat Slessarev, MD, PhD,
Eileen Campbell,
John Basmaji, MD,
Ian Ball, MD,
Douglas D. Fraser, MD, PhD,
Aleksandra Leligdowicz, MD, PhD,
Tina Mele, MD, PhD,
Fran Priestap, MSc,
Brent J. Tschirhart, MSc,
Tracey Bentall, RN,
Xiangru Lu, MD,
Qingping Feng, MD, PhD

Affiliations

Claudio M. Martin, MD: 1 Division of Critical Care Medicine, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Marat Slessarev, MD, PhD: 1 Division of Critical Care Medicine, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Eileen Campbell: 2 Lawson Health Research Institute, London Health Sciences Centre, London, ON, Canada.
John Basmaji, MD: 1 Division of Critical Care Medicine, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Ian Ball, MD: 1 Division of Critical Care Medicine, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Douglas D. Fraser, MD, PhD: 2 Lawson Health Research Institute, London Health Sciences Centre, London, ON, Canada.
Aleksandra Leligdowicz, MD, PhD: 1 Division of Critical Care Medicine, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Tina Mele, MD, PhD: 1 Division of Critical Care Medicine, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Fran Priestap, MSc: 1 Division of Critical Care Medicine, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Brent J. Tschirhart, MSc: 2 Lawson Health Research Institute, London Health Sciences Centre, London, ON, Canada.
Tracey Bentall, RN: 2 Lawson Health Research Institute, London Health Sciences Centre, London, ON, Canada.
Xiangru Lu, MD: 5 Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Qingping Feng, MD, PhD: 2 Lawson Health Research Institute, London Health Sciences Centre, London, ON, Canada.

DOI: https://doi.org/10.1097/CCE.0000000000000986
Journal volume & issue: Vol. 5, no. 10
p. e0986

Abstract

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OBJECTIVES:. To evaluate the study design and feasibility of drug administration and safety in a randomized clinical trial of recombinant human annexin A5 (SY-005), a constitutively expressed protein with anti-inflammatory, antiapoptotic, and anticoagulant properties, in patients with severe coronavirus disease 2019 (COVID-19). DESIGN:. Double-blind, randomized clinical trial. SETTING:. Two ICUs at an academic medical center. PATIENTS/SUBJECTS:. Adults admitted to the ICU with a confirmed diagnosis of COVID-19 and requiring ventilatory or vasopressor support. INTERVENTIONS:. SY-005, a recombinant human annexin A5, at 50 or 100 µg/kg IV every 12 hours for 7 days. MEASUREMENTS AND MAIN RESULTS:. We enrolled 18 of the 55 eligible patients (33%) between April 21, 2021, and February 3, 2022. We administered 82% (196/238) of the anticipated doses of study medication and 86% (169/196) were given within 1 hour of the scheduled time. There were no drug-related serious adverse events. We captured 100% of the data that would be required for measuring clinical outcomes in a phase 2 or 3 trial. LIMITATIONS:. The small sample size was a result of decreasing admissions of patients with COVID-19, which triggered a stopping rule for the trial. CONCLUSIONS:. Although enrollment was low, administration of SY-005 to critically ill patients with COVID-19 every 12 hours for up to 7 days was feasible and safe. Further clinical trials of annexin A5 for the treatment of COVID-19 are warranted. Given reduction of severe COVID-19 disease, future studies should explore the safety and effectiveness of SY-005 use in non-COVID-related sepsis.

Published in Critical Care Explorations

ISSN: 2639-8028 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Medical emergencies. Critical care. Intensive care. First aid
Website: https://journals.lww.com/ccejournal/pages/default.aspx

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