A Novel Immune Modulator for Patients With Necrotizing Soft Tissue Infections (NSTI): Results of a Multicenter, Phase 3 Randomized Controlled Trial of Reltecimod (AB 103).

Autor:	Bulger EM; University of Washington, Harborview Medical Center, Seattle, Washington., May AK; Atrium Health, Charlotte, North Carolina., Robinson BRH; University of Washington, Harborview Medical Center, Seattle, Washington., Evans DC; Ohio Health, Grant & Mansfield Hospitals, Columbus, Ohio., Henry S; University of Maryland, Baltimore, Maryland., Green JM; Carolinas Medical Center, Charlotte, North Carolina., Toschlog E; East Carolina University, Greenville, North Carolina., Sperry JL; University of Pittsburgh, Pittsburgh, Pennsylvania., Fagenholz P; Massachusetts General Hospital, Boston, Massachusetts., Martin ND; University of Pennsylvania, Philadelphia, Pennsylvania., Dankner WM; Atox Bio Ltd, Durham, North Carolina., Maislin G; Biomedical Statistical Consulting, Wynnewood, Pennsylvania., Wilfret D; Atox Bio Ltd, Durham, North Carolina., Bernard AC; University of Kentucky, Lexington, Kentucky.
Jazyk:	angličtina
Zdroj:	Annals of surgery [Ann Surg] 2020 Sep 01; Vol. 272 (3), pp. 469-478.
DOI:	10.1097/SLA.0000000000004102
Abstrakt:	Background and Objective: Reltecimod, a CD 28 T-lymphocyte receptor mimetic, inhibits T-cell stimulation by an array of bacterial pathogens. A previous phase 2 trial demonstrated improved resolution of organ dysfunction after NSTI. We hypothesized that early administration of reltecimod would improve outcome in severe NSTI. Methods: Randomized, double-blind, placebo-controlled trial of single dose reltecimod (0.5 mg/kg) administered within 6 hours of NSTI diagnosis at 65 of 93 study sites. Inclusion: surgical confirmation of NSTI and organ dysfunction [modified Sequential Organ Failure Assessment Score (mSOFA) score ≥3]. Primary analysis was modified Intent-to-Treat (mITT), responder analysis using a previously validated composite endpoint, necrotizing infection clinical composite endpoint, defined as: alive at day 28, ≤3 debridements, no amputation beyond first operation, and day 14 mSOFA ≤1 with ≥3 point reduction (organ dysfunction resolution). A prespecified, per protocol (PP) analysis excluded 17 patients with major protocol violations before unblinding. Results: Two hundred ninety patients were enrolled, mITT (Reltecimod 142, Placebo 148): mean age 55 ± 15 years, 60% male, 42.4% diabetic, 28.6% perineal infection, screening mSOFA mean 5.5 ± 2.4. Twenty-eight-day mortality was 15% in both groups. mITT necrotizing infection clinical composite endpoint success was 48.6% reltecimod versus 39.9% placebo, P = 0.135 and PP was 54.3% reltecimod versus 40.3% placebo, P = 0.021. Resolution of organ dysfunction was 65.1% reltecimod versus 52.6% placebo, P = 0.041, mITT and 70.9% versus 53.4%, P = 0.005, PP. Conclusion: Early administration of reltecimod in severe NSTI resulted in a significant improvement in the primary composite endpoint in the PP population but not in the mITT population. Reltecimod was associated with improved resolution of organ dysfunction and hospital discharge status. Competing Interests: The authors have no other conflicts of interests to disclose. (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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