Format

Send to

Choose Destination
JAMA Surg. 2014 Jun;149(6):528-36. doi: 10.1001/jamasurg.2013.4841.

A Novel Drug for Treatment of Necrotizing Soft-Tissue Infections: A Randomized Clinical Trial.

Author information

1
Department of Surgery, Harborview Medical Center, University of Washington, Seattle.
2
University of Pittsburgh, Pittsburgh, Pennsylvania.
3
Department of Surgery and Medicine, University of Maryland, Baltimore.
4
Department of Surgery, University of Florida, Gainesville.
5
Department of Surgery, University of Southern California, Los Angeles.
6
Department of Surgery, Oregon Health & Science University, Portland.
7
Department of Surgery, University of California, San Francisco.
8
Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island.
9
Atox Bio Ltd, Ness Ziona, Israel.
10
Biomedical Statistical Consulting, Wynnewood, Pennsylvania.
11
Atox Bio Ltd, Ness Ziona, Israel11Department of Molecular Biology, Hebrew University Hadassah Medical School, Jerusalem, Israel.

Abstract

IMPORTANCE:

Necrotizing soft-tissue infections (NSTI) have high morbidity and mortality rates despite aggressive surgical debridement and antibiotic therapy. AB103 is a peptide mimetic of the T-lymphocyte receptor, CD28. We hypothesized that AB103 will limit inflammatory responses to bacterial toxins and decrease the incidence of organ failure.

OBJECTIVES:

To establish the safety of AB103 in patients with NSTI and evaluate the potential effects on clinically meaningful parameters related to the disease.

DESIGN, SETTING, AND PARTICIPANTS:

A prospective, randomized, placebo-controlled, double-blinded study was performed in 6 academic medical centers in the United States. Participants included adults with NSTI. Of 345 patients screened, 43 were enrolled for the intent-to-treat analysis, and 40 met criteria for the modified intent-to-treat analysis; 15 patients each were included in the high-dose and low-dose treatment arms, and 10 in the placebo arm.

INTERVENTION:

Single intravenous dose of AB103 (0.5 or 0.25 mg/kg) within 6 hours after diagnosis of NSTI.

MAIN OUTCOMES AND MEASURES:

Change in the Sequential Organ Failure Assessment score within 28 days, intensive care unit-free and ventilator-free days, number and timing of debridements, plasma and tissue cytokine levels at 0 to 72 hours, and adverse events.

RESULTS:

Baseline characteristics were comparable in the treatment groups. The Sequential Organ Failure Assessment score improved from baseline in both treatment groups compared with the placebo group at 14 days (change from baseline score, -2.8 in the high-dose, -2 in the low-dose, and +1.3 in the placebo groups; P = .04). AB103-treated patients had a similar number of debridements (mean [SD], 2.2 [1.1] for the high-dose, 2.3 [1.2] for the low-dose, and 2.8 [2.1] for the placebo groups; P = .56). There were no statistically significant differences in intensive care unit-free and ventilator-free days or in plasma and tissue cytokine levels. No drug-related adverse events were detected.

CONCLUSIONS AND RELEVANCE:

AB103 is a safe, promising new agent for modulation of inflammation after NSTI. Further study is warranted to establish efficacy.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT01417780.

PMID:
24740134
DOI:
10.1001/jamasurg.2013.4841
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center