tetano
Editor, Senior Moderator
BMJ Open
. 2024 Mar 15;14(3):e076142.
doi: 10.1136/bmjopen-2023-076142. Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19)
Ranjani Somayaji[SUP] 1 2 3 4 [/SUP], David R Luke[SUP] 5 [/SUP], Arthur Lau[SUP] 6 5 [/SUP], Rahmet Guner[SUP] 7 [/SUP], Ŏ Fehmi Tabak[SUP] 7 [/SUP], Mark Hepokoski[SUP] 8 9 [/SUP], Nancy Gardetto[SUP] 8 9 [/SUP], Steven A Conrad[SUP] 10 [/SUP], Sunil D Kumar[SUP] 11 [/SUP], Kalyan Ghosh[SUP] 12 [/SUP], Stephen M Robbins[SUP] 13 14 15 [/SUP], Donna L Senger[SUP] 13 14 15 [/SUP], Daisy Sun[SUP] 5 [/SUP], Rachel K S Lim[SUP] 6 [/SUP], Jonathan Liu[SUP] 6 [/SUP], Fatma Eser[SUP] 16 [/SUP], Ridvan Karaali[SUP] 7 [/SUP], Alain Tremblay[SUP] 6 4 [/SUP], Daniel Muruve[SUP] 6 2 4 [/SUP]
Affiliations
Objective: Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19.
Design: Phase 2a randomised, placebo-controlled, double-blinded, trial.
Setting: Hospitals in Canada, Turkey and the USA.
Participants: A total of 61 subjects with moderate-to-severe COVID-19.
Interventions: Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days.
Primary and secondary outcome measures: The primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers.
Results: At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O[SUB]2[/SUB] ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups.
Conclusion: In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19.
Trial registration number: NCT04402957.
Keywords: COVID-19; Clinical Trial; INFECTIOUS DISEASES; Safety.
. 2024 Mar 15;14(3):e076142.
doi: 10.1136/bmjopen-2023-076142. Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19)
Ranjani Somayaji[SUP] 1 2 3 4 [/SUP], David R Luke[SUP] 5 [/SUP], Arthur Lau[SUP] 6 5 [/SUP], Rahmet Guner[SUP] 7 [/SUP], Ŏ Fehmi Tabak[SUP] 7 [/SUP], Mark Hepokoski[SUP] 8 9 [/SUP], Nancy Gardetto[SUP] 8 9 [/SUP], Steven A Conrad[SUP] 10 [/SUP], Sunil D Kumar[SUP] 11 [/SUP], Kalyan Ghosh[SUP] 12 [/SUP], Stephen M Robbins[SUP] 13 14 15 [/SUP], Donna L Senger[SUP] 13 14 15 [/SUP], Daisy Sun[SUP] 5 [/SUP], Rachel K S Lim[SUP] 6 [/SUP], Jonathan Liu[SUP] 6 [/SUP], Fatma Eser[SUP] 16 [/SUP], Ridvan Karaali[SUP] 7 [/SUP], Alain Tremblay[SUP] 6 4 [/SUP], Daniel Muruve[SUP] 6 2 4 [/SUP]
Affiliations
- PMID: 38490660
- PMCID: PMC10946381
- DOI: 10.1136/bmjopen-2023-076142
Objective: Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19.
Design: Phase 2a randomised, placebo-controlled, double-blinded, trial.
Setting: Hospitals in Canada, Turkey and the USA.
Participants: A total of 61 subjects with moderate-to-severe COVID-19.
Interventions: Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days.
Primary and secondary outcome measures: The primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers.
Results: At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O[SUB]2[/SUB] ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups.
Conclusion: In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19.
Trial registration number: NCT04402957.
Keywords: COVID-19; Clinical Trial; INFECTIOUS DISEASES; Safety.