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Targeting CXCR1/2 Does Not Improve Insulin Secretion After Pancreatic Islet Transplantation : A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial in Type 1 Diabetes

Maffi, Paola ; Lundgren, Torbjörn ; Tufveson, Gunnar ; Rafael, Ehab LU ; Shaw, James A.M. ; Liew, Aaron ; Saudek, Frantisek ; Witkowski, Piotr ; Golab, Karolina and Bertuzzi, Federico , et al. (2020) In Diabetes Care 43(4). p.710-718
Abstract

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 ± 5 after the first and day 365 ± 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... (More)

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 ± 5 after the first and day 365 ± 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 = 0.99) and day 365 (24 on reparixin vs. 15 on placebo, P = 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 = 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.

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author collaboration
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes Care
volume
43
issue
4
pages
9 pages
publisher
American Diabetes Association
external identifiers
  • scopus:85082148145
  • pmid:32019854
ISSN
1935-5548
DOI
10.2337/dc19-1480
language
English
LU publication?
no
id
7bac1434-3623-402b-b675-cae6cd88f342
date added to LUP
2020-04-03 09:33:11
date last changed
2024-05-29 10:28:27
@misc{7bac1434-3623-402b-b675-cae6cd88f342,
  abstract     = {{<p>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 ± 5 after the first and day 365 ± 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 = 0.99) and day 365 (24 on reparixin vs. 15 on placebo, P = 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 = 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.</p>}},
  author       = {{Maffi, Paola and Lundgren, Torbjörn and Tufveson, Gunnar and Rafael, Ehab and Shaw, James A.M. and Liew, Aaron and Saudek, Frantisek and Witkowski, Piotr and Golab, Karolina and Bertuzzi, Federico and Gustafsson, Bengt and Daffonchio, Luisa and Ruffini, Pier Adelchi and Piemonti, Lorenzo}},
  issn         = {{1935-5548}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{710--718}},
  publisher    = {{American Diabetes Association}},
  series       = {{Diabetes Care}},
  title        = {{Targeting CXCR1/2 Does Not Improve Insulin Secretion After Pancreatic Islet Transplantation : A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial in Type 1 Diabetes}},
  url          = {{http://dx.doi.org/10.2337/dc19-1480}},
  doi          = {{10.2337/dc19-1480}},
  volume       = {{43}},
  year         = {{2020}},
}