Abstract: Open access
Original research
Ranjani Somayaji ,1,2,3,4 David R Luke,5 Arthur Lau,1,5 Rahmet Guner,6
Ŏ Fehmi Tabak,6 Mark Hepokoski,7,8 Nancy Gardetto,7,8 Steven A Conrad ,9
Sunil D Kumar,10 Kalyan Ghosh,11 Stephen M Robbins,12,13,14 Donna L Senger,12,13,14
Daisy Sun,5 Rachel K S Lim,1 Jonathan Liu,1 Fatma Eser ,15 Ridvan Karaali,6
Alain Tremblay,1,4 Daniel Muruve 1,2,4
To cite: Somayaji R, Luke DR,
Lau A, et al. 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-1 9). BMJ Open
2024;14:e076142. doi:10.1136/
bmjopen-2023-076142
► Prepublication history
and additional supplemental
material for this paper are
available online. To view these
files, please visit the journal
online (https://doi.org/10.1136/
bmjopen-2023-076142).
Received 30 May 2023
Accepted 26 February 2024
© Author(s) (or their
employer(s)) 2024. Re-use
permitted under CC BY-NC. No
commercial re-use. See rights
and permissions. Published by
BMJ.
For numbered affiliations see
end of article.
Correspondence to
Dr Ranjani Somayaji;
r somayaj@ucalgary.ca
ABSTRACT
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 (O2 ≥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.
STRENGTHS AND LIMITATIONS OF THIS STUDY
⇒ Phase
2 randomised double-
blind placebo-
controlled multi-centre design.
⇒ International study cohort to enhance generalisability.
⇒ Demonstrated safety and tolerance of LSALT peptide in persons with moderate-to-severe COVID-19
infection.
⇒ Underpowered to identify significant differences in
clinical efficacy.
SUMMARY..
DOI record:
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"abstract": "<jats:sec><jats:title>Objective</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Phase 2a randomised, placebo-controlled, double-blinded, trial.</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>Hospitals in Canada, Turkey and the USA.</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>A total of 61 subjects with moderate-to-severe COVID-19.</jats:p></jats:sec><jats:sec><jats:title>Interventions</jats:title><jats:p>Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days.</jats:p></jats:sec><jats:sec><jats:title>Primary and secondary outcome measures</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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<jats:sub>2</jats: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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19.</jats:p></jats:sec><jats:sec><jats:title>Trial registration number</jats:title><jats:p><jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial \" xlink:href=\"NCT04402957\">NCT04402957</jats:ext-link>.</jats:p></jats:sec>",
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