Immunoglobulin G for patients with necrotising soft tissue infection (INSTINCT): a randomised, blinded, placebo-controlled trial
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The aim of the INSTINCT trial was to assess the effect of intravenous polyspecific immunoglobulin G (IVIG) compared with placebo on self-reported physical function in intensive care unit (ICU) patients with necrotising soft tissue infection (NSTI).
We randomised 100 patients with NSTI 1:1 to masked infusion of 25 g of IVIG (Privigen, CSL Behring) or an equal volume of 0.9% saline once daily for the first 3 days of ICU admission. The primary outcome was the physical component summary (PCS) score of the 36-item short form health survey (SF-36) 6 months after randomisation; patients who had died were given the lowest possible score (zero).
Of the 100 patients randomised, 87 were included in the intention-to-treat analysis of the PCS score, 42 patients (84%) in the IVIG group and 45 patients (90%) in the placebo group. The two intervention groups had similar baseline characteristics with the exception of IVIG use before randomisation (1 dose was allowed) and rates of acute kidney injury. Median PCS scores were 36 (interquartile range 0–43) in the group assigned to IVIG and 31 (0–47) in the group assigned to placebo (mean adjusted difference 1 (95% confidence interval −7 to 10), p = 0.81). The result was supported by analyses adjusted for baseline prognostics, those in the per protocol populations, in the subgroups (site of NSTI) and those done post hoc adjusted for IVIG use before randomisation.
In ICU patients with NSTI, we observed no apparent effects of adjuvant IVIG on self-reported physical functioning at 6 months.
Trial registration: NCT02111161.
KeywordsFournier’s gangrene Necrotising fasciitis Patient-reported outcome measure Quality of life Sepsis SF-36
We are grateful to the doctors and nurses at Copenhagen University Hospital, Rigshospitalet, to the research staff at the ICU and to the INFECT team for their important contributions and to patients and relatives for their consent to participate.
Compliance with ethical standards
Conflicts of interest
The INSTINCT trial was supported by CSL Behring in the form of trial medication and a research grant for trial conduct, a research nurse and the statistical analyses. CSL Behring had no role in study design, data collection, analysis or interpretation, or writing of the report. MBM and AP conceived the idea and wrote the trial protocol. The trial group has no obligations to CSL Behring, and none of the authors have affiliations to or receive honoraria or funds from CSL Behring. The trial is part of the INFECT project (NCT01790698), supported by the European Union’s Seventh Framework Programme.
The Department of Intensive Care, Rigshospitalet, receives research funds from Fresenius Kabi, Germany, and Ferring Pharmaceuticals, Denmark.
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