Salovum® reduces mortality in isolated severe traumatic brain injury: a randomized phase II trial.

Abstract

Isolated severe traumatic brain injury (TBI) is associated with high mortality and long-term morbidity, especially in low- and middle-income countries (LMICs). Despite promising results using pharmacological and non-pharmacological therapies in the experimental setting, no clinical trials have demonstrated robust efficacy. We aimed to investigate the effect of antisecretory factor (Salovum®) on 30-day mortality in adult patients with severe TBI. This was a prospective, double-blind, placebo-controlled phase 2 trial, conducted from September 2017 to February 2022 in a tertiary trauma centre (university hospital) in Cape Town, South Africa (www.clinicaltrials.gov: NCT03339505). The participants were adults with isolated severe TBI (Glasgow Coma Score 6-8), receiving intracranial pressure (ICP) monitoring and neurointensive care. Participants were administered either Salovum® (freeze-dried egg yolk powder enriched with the active compound antisecretory factor) or placebo (freeze dried egg yolk powder) via the nasogastric tubing, dosed according to weight (10-17 g/4 h) and initiated at 32.9 h ± 10.7 h (mean ± standard deviation) post-injury. Study drug or placebo were administered until the ICP monitor was removed or for a maximum of 5 days. The primary outcome of this trial was 30-day mortality and secondary outcome measures were therapy intensity level (TIL) and ICP. One hundred participants aged 18-61 were included, with 49 and 51 patients in the treatment and control groups, respectively. Most patients were male (96%) and the mean age was 33 years. The 30-day mortality rate was 20% in the treatment group and 39% in the control group, yielding a relative risk ratio of 0.52 (confidence interval: 0.271-0.997) and a P-value of 0.040 (chi-square test). TIL and ICP were similar in both groups. No significant adverse events were noted. Antisecretory factor significantly reduced 30-day mortality in severe TBI in an LMIC environment. Further studies investigating the mechanisms by which antisecretory factor act are warranted. The safety, easy administration and marked efficacy of antisecretory factor support exploration in multicentre randomized controlled trials.