Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

STOP-COVID19 Investigators; Holly R  Keir; Merete Long; Hani Abo-Leyah; Yan Hui Giam; Thenmalar Vadiveloo; Thomas Pembridge; Rebecca C Hull; Liloa  Delgado; Margaret Band; Fiona McLaren-Neil; Simon Adamson; Eva Lahnsteiner; Amy Gilmour; Chole Hughes; Benjamin JM New; David Connell; Rebecca Dowey; Helena Turton; Hollian  Richardson; Diane Cassidy; Jamie Cooper; Jay Suntharalingam; Lavanya Diwakar; Peter  Russell; Jonathan Underwood; Alexander Hicks; Davinder Ps Dosanjh; Beth Sage; Devesh Dhasmana; Mark Spears; A A Roger Thompson; Christopher Brightling; Andrew  Smith; Manish Patel; Jacob George; Alison M Condliffe; Amelia Shoemark; Graeme Maclennan; James D Chalmers

doi:10.1016/S2213-2600(22)00261-2

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

STOP-COVID19 Investigators, Holly R Keir, Merete Long, Hani Abo-Leyah, Yan Hui Giam, Thenmalar Vadiveloo, Thomas Pembridge, Rebecca C Hull, Liloa Delgado, Margaret Band, Fiona McLaren-Neil, Simon Adamson, Eva Lahnsteiner, Amy Gilmour, Chole Hughes, Benjamin JM New, David Connell, Rebecca Dowey, Helena Turton, Hollian RichardsonDiane Cassidy, Jamie Cooper, Jay Suntharalingam, Lavanya Diwakar, Peter Russell, Jonathan Underwood, Alexander Hicks, Davinder Ps Dosanjh, Beth Sage, Devesh Dhasmana, Mark Spears, A A Roger Thompson, Christopher Brightling, Andrew Smith, Manish Patel, Jacob George, Alison M Condliffe, Amelia Shoemark, Graeme Maclennan, James D Chalmers

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

Abstract

Background: Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19.

Methods: In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in

Original language	English
Pages (from-to)	1119-1128
Number of pages	10
Journal	The Lancet Respiratory Medicine
Volume	10
Issue number	12
Early online date	29 Nov 2022
DOIs	https://doi.org/10.1016/S2213-2600(22)00261-2
Publication status	Published - 10 Dec 2022
Externally published	Yes

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STOP-COVID19 Investigators, Keir, H. R., Long, M., Abo-Leyah, H., Hui Giam, Y., Vadiveloo, T., Pembridge, T., Hull, R. C., Delgado, L., Band, M., McLaren-Neil, F., Adamson, S., Lahnsteiner, E., Gilmour, A., Hughes, C., New, B. JM., Connell, D., Dowey, R., Turton, H., ... Chalmers, J. D. (2022). Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. The Lancet Respiratory Medicine, 10(12), 1119-1128. https://doi.org/10.1016/S2213-2600(22)00261-2

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title = "Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial",

abstract = "Background: Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods: In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in ",

keywords = "brensocatib, dipeptidyl peptidase-1, COVID-19",

author = "\{STOP-COVID19 Investigators\} and Keir, \{Holly R\} and Merete Long and Hani Abo-Leyah and \{Hui Giam\}, Yan and Thenmalar Vadiveloo and Thomas Pembridge and Hull, \{Rebecca C\} and Liloa Delgado and Margaret Band and Fiona McLaren-Neil and Simon Adamson and Eva Lahnsteiner and Amy Gilmour and Chole Hughes and New, \{Benjamin JM\} and David Connell and Rebecca Dowey and Helena Turton and Hollian Richardson and Diane Cassidy and Jamie Cooper and Jay Suntharalingam and Lavanya Diwakar and Peter Russell and Jonathan Underwood and Alexander Hicks and Dosanjh, \{Davinder Ps\} and Beth Sage and Devesh Dhasmana and Mark Spears and Thompson, \{A A Roger\} and Christopher Brightling and Andrew Smith and Manish Patel and Jacob George and Condliffe, \{Alison M\} and Amelia Shoemark and Graeme Maclennan and Chalmers, \{James D\}",

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STOP-COVID19 Investigators, Keir, HR, Long, M, Abo-Leyah, H, Hui Giam, Y, Vadiveloo, T, Pembridge, T, Hull, RC, Delgado, L, Band, M, McLaren-Neil, F, Adamson, S, Lahnsteiner, E, Gilmour, A, Hughes, C, New, BJM, Connell, D, Dowey, R, Turton, H, Richardson, H, Cassidy, D, Cooper, J, Suntharalingam, J, Diwakar, L, Russell, P, Underwood, J, Hicks, A, Dosanjh, DP, Sage, B, Dhasmana, D, Spears, M, Thompson, AAR, Brightling, C, Smith, A, Patel, M, George, J, Condliffe, AM, Shoemark, A, Maclennan, G & Chalmers, JD 2022, 'Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial', The Lancet Respiratory Medicine, vol. 10, no. 12, pp. 1119-1128. https://doi.org/10.1016/S2213-2600(22)00261-2

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. / STOP-COVID19 Investigators; Keir, Holly R; Long, Merete et al.
In: The Lancet Respiratory Medicine, Vol. 10, No. 12, 10.12.2022, p. 1119-1128.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19

T2 - a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

AU - STOP-COVID19 Investigators

AU - Keir, Holly R

AU - Long, Merete

AU - Abo-Leyah, Hani

AU - Hui Giam, Yan

AU - Vadiveloo, Thenmalar

AU - Pembridge, Thomas

AU - Hull, Rebecca C

AU - Delgado, Liloa

AU - Band, Margaret

AU - McLaren-Neil, Fiona

AU - Adamson, Simon

AU - Lahnsteiner, Eva

AU - Gilmour, Amy

AU - Hughes, Chole

AU - New, Benjamin JM

AU - Connell, David

AU - Dowey, Rebecca

AU - Turton, Helena

AU - Richardson, Hollian

AU - Cassidy, Diane

AU - Cooper, Jamie

AU - Suntharalingam, Jay

AU - Diwakar, Lavanya

AU - Russell, Peter

AU - Underwood, Jonathan

AU - Hicks, Alexander

AU - Dosanjh, Davinder Ps

AU - Sage, Beth

AU - Dhasmana, Devesh

AU - Spears, Mark

AU - Thompson, A A Roger

AU - Brightling, Christopher

AU - Smith, Andrew

AU - Patel, Manish

AU - George, Jacob

AU - Condliffe, Alison M

AU - Shoemark, Amelia

AU - Maclennan, Graeme

AU - Chalmers, James D

PY - 2022/12/10

Y1 - 2022/12/10

N2 - Background: Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods: In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in

AB - Background: Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods: In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in

KW - brensocatib

KW - dipeptidyl peptidase-1

KW - COVID-19

U2 - 10.1016/S2213-2600(22)00261-2

DO - 10.1016/S2213-2600(22)00261-2

M3 - Article

SN - 2213-2600

VL - 10

SP - 1119

EP - 1128

JO - The Lancet Respiratory Medicine

JF - The Lancet Respiratory Medicine

IS - 12

ER -

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Abstract

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