Immunoglobulin for necrotising soft tissue infections (INSTINCT): protocol for a randomised trial

INTRODUCTION: Necrotising soft tissue infections (NSTI) are aggressive infections that can result in severe disability or death. Intravenous polyspecific immunoglobulin G (IVIG) is used as supplementary treatment for patients with NSTIs. The level of evidence is very low, but suggests that IVIG may have beneficial effects. However, IVIG may also have adverse effects. With this trial we will estimate the effects of IVIG on a patient-reported outcome and other patient-centred outcomes in patients with NSTI.

METHODS: INSTINCT is a randomised, double-blinded, parallel-group, placebo-controlled trial with concealed allocation of patients with NSTI 1:1 to IVIG or an equal volume of 0.9% saline. Patients are recruited at Rigshospitalet, Denmark. The primary outcome is the physical component summary score of the Medical Outcomes Study 36-Item Short-Form Health Survey as assessed six months after randomisation. Secondary outcomes are: mortality; time to resolution of shock; bleeding; sequential organ failure assessment scores on days 1-7; use of renal-replacement therapy, mechanical ventilation and vasopressors; days alive and out of hospital; amputation; and severe adverse reactions.

CONCLUSION: This study will be the only completed trial testing IVIG for NSTI, thereby providing important data on a severely sick patient group.

FUNDING: The trial is supported by CSL Behring in the form of trial medication and a € 92,182 grant for trial conduct, research, nurse salary and statistical analyses.

TRIAL REGISTRATION: The trial is registered with clinicaltrials.gov (NCT02111161). .