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Lookup NU author(s): Professor James Shaw, Dr Aaron Liew
This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Diabetes Association Inc., 2020.
For re-use rights please refer to the publisher's terms and conditions.
© 2020 by the American Diabetes Association.OBJECTIVE Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients. RESEARCH DESIGN AND METHODS A phase 3, multicenter, randomized, double-blind, parallel-assignment study (NCT01817959) was conducted in recipients of islet allotransplants randomized (2:1) to reparixin or placebo in addition to immunosuppression. Primary outcome was the area under the curve (AUC) for C-peptide during the mixed-meal tolerance test at day 75 6 5 after the first and day 365 6 14 after the last transplant. Secondary end points included insulin independence and standard measures of glycemic control. RESULTS The intention-to-treat analysis did not show a significant difference in C-peptide AUC at both day 75 (27 on reparixin vs. 18 on placebo, P 5 0.99) and day 365 (24 on reparixin vs. 15 on placebo, P 5 0.71). There was no statistically significant difference between treatment groups at any time point for any secondary variable. Analysis of patient subsets showed a trend for a higher percentage of subjects retaining insulin independence for 1 year after a single islet infusion in patients receiving reparixin as compared with patients receiving placebo (26.7% vs. 0%, P 5 0.09) when antithymocyte globulin was used as induction immunosuppression. CONCLUSIONS In this first double-blind randomized trial, islet transplantation data obtained with reparixin do not support a role of CXCR1/2 inhibition in preventing islet inflammation-mediated damage.
Author(s): Maffi P, Lundgren T, Tufveson G, Rafael E, Shaw JAM, Liew A, Saudek F, Witkowski P, Golab K, Bertuzzi F, Gustafsson B, Daffonchio L, Ruffini PA, Piemonti L, Nano R, Mercalli A, Lampasona V, Magistretti P, Sordi V, Antonio S, Antonioli B, Galuzzi M, Tosca MC, De Carlis L, Colussi G, Korsgren O, Pollard H
Publication type: Article
Publication status: Published
Journal: Diabetes Care
Year: 2020
Volume: 43
Issue: 4
Pages: 710-718
Print publication date: 20/03/2020
Online publication date: 04/02/2020
Acceptance date: 11/12/2019
Date deposited: 30/04/2020
ISSN (print): 0149-5992
ISSN (electronic): 1935-5548
Publisher: American Diabetes Association Inc.
URL: https://doi.org/10.2337/dc19-1480
DOI: 10.2337/dc19-1480
PubMed id: 32019854
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