tetano
Editor, Senior Moderator
Crit Care Explor
. 2023 Oct 5;5(10):e0986.
doi: 10.1097/CCE.0000000000000986. eCollection 2023 Oct. Annexin A5 in Patients With Severe COVID-19 Disease: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Feasibility Trial
Claudio M Martin[SUP] 1 2 [/SUP], Marat Slessarev[SUP] 1 2 [/SUP], Eileen Campbell[SUP] 2 [/SUP], John Basmaji[SUP] 1 2 [/SUP], Ian Ball[SUP] 1 2 3 [/SUP], Douglas D Fraser[SUP] 2 4 [/SUP], Aleksandra Leligdowicz[SUP] 1 2 [/SUP], Tina Mele[SUP] 1 2 5 [/SUP], Fran Priestap[SUP] 1 2 [/SUP], Brent J Tschirhart[SUP] 2 6 [/SUP], Tracey Bentall[SUP] 2 [/SUP], Xiangru Lu[SUP] 5 [/SUP], Qingping Feng[SUP] 2 6 [/SUP]
Affiliations
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.
Keywords: SY-005; annexin A5; feasibility; safety; sepsis; severe coronavirus disease 2019.
. 2023 Oct 5;5(10):e0986.
doi: 10.1097/CCE.0000000000000986. eCollection 2023 Oct. Annexin A5 in Patients With Severe COVID-19 Disease: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Feasibility Trial
Claudio M Martin[SUP] 1 2 [/SUP], Marat Slessarev[SUP] 1 2 [/SUP], Eileen Campbell[SUP] 2 [/SUP], John Basmaji[SUP] 1 2 [/SUP], Ian Ball[SUP] 1 2 3 [/SUP], Douglas D Fraser[SUP] 2 4 [/SUP], Aleksandra Leligdowicz[SUP] 1 2 [/SUP], Tina Mele[SUP] 1 2 5 [/SUP], Fran Priestap[SUP] 1 2 [/SUP], Brent J Tschirhart[SUP] 2 6 [/SUP], Tracey Bentall[SUP] 2 [/SUP], Xiangru Lu[SUP] 5 [/SUP], Qingping Feng[SUP] 2 6 [/SUP]
Affiliations
- PMID: 37811130
- PMCID: PMC10558223
- DOI: 10.1097/CCE.0000000000000986
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.
Keywords: SY-005; annexin A5; feasibility; safety; sepsis; severe coronavirus disease 2019.