Daijiworld Media Network - Bengaluru

Bengaluru, Sep 15: A phase II clinical trial has found that treatment with antisecretory factor significantly reduced 30-day mortality among adults with severe traumatic brain injury (TBI), raising hopes for a potentially low-cost treatment option, particularly in low- and middle-income countries where access to advanced neurocritical care remains limited.

The prospective, double-blind, placebo-controlled trial was conducted from September 2017 to February 2022 at Tygerberg Academic Hospital, a tertiary trauma centre in Cape Town, South Africa. The study involved 100 adults aged between 18 and 61 years with isolated severe TBI, a Glasgow Coma Scale (GCS) score of 6 to 8 and a clinical requirement for intracranial pressure (ICP) monitoring.

Participants were randomly assigned to receive either Salovum, an egg-yolk powder enriched with antisecretory factor, or a placebo consisting of freeze-dried egg-yolk powder. The treatment was administered through a nasogastric tube according to body weight, at doses of 10 to 17 grams every four hours. Treatment began at an average of about 32.9 hours after the injury and continued until removal of the ICP monitor or for a maximum of five days.

Of the 100 participants, 49 received Salovum while 51 received the placebo. The study population was predominantly male, with men accounting for 96 per cent of participants, and the mean age was 33 years.

The primary outcome was mortality 30 days after the injury. Researchers found that 20 per cent of patients in the Salovum group died within 30 days, compared with 39 per cent in the placebo group.

This represented a relative risk of 0.52, with a 95 per cent confidence interval of 0.271 to 0.997 and a P-value of 0.040. The findings therefore showed a statistically significant reduction in 30-day mortality among patients who received antisecretory factor therapy.

However, researchers found no significant difference between the two groups in therapy intensity level (TIL) or intracranial pressure. No significant adverse events were reported in either group.

Antisecretory factor (AF) is a naturally occurring 41-kDa protein with antisecretory and anti-inflammatory properties. Salovum is a freeze-dried egg-yolk preparation containing high concentrations of AF and AF-derived peptides and is classified as a food for special medical purposes in the European Union and United States.

The precise mechanism through which AF may influence outcomes after severe TBI remains uncertain. Experimental research has suggested that it could affect processes involved in cerebral oedema and inflammation. Researchers have pointed to possible effects involving the NKCC1 ion pump, which is associated with disruption of the blood-brain barrier and development of brain swelling, while other research has suggested a role in regulating inflammatory pathways.

The latest findings build on earlier preliminary work. A small clinical case series involving five adults with severe TBI had previously reported possible reductions in intracranial pressure and no observed toxicity following Salovum treatment. Another pilot study involving four patients suggested that AF could help control elevated intracranial pressure associated with traumatic brain oedema.

The researchers said the new randomised trial provides the first statistically significant clinical evidence of a mortality benefit from antisecretory factor in severe TBI. The study is particularly relevant to resource-limited settings because Salovum can be administered through a nasogastric tube and does not require the complex infrastructure associated with some advanced neurocritical interventions.

The study was conducted in a low- and middle-income-country setting, where severe TBI is associated with substantial mortality and long-term disability and access to specialised neurocritical care can be limited. Researchers said the favourable safety profile, ease of administration and apparent mortality benefit warrant further investigation.

At the same time, the investigators cautioned that the results need to be validated in larger, multicentre randomised controlled trials before the therapy can be considered for routine management of severe TBI. The present study was conducted at a single centre and included only 100 patients, limiting the extent to which the findings can be generalised to wider patient populations.

Further research is also under way to better understand how antisecretory factor works in severe TBI. A separate clinical study is examining Salovum alongside multimodal monitoring, including intracranial pressure, brain oxygenation, microdialysis and inflammatory markers, in an effort to clarify its biological effects.

The researchers concluded that the significant reduction in 30-day mortality, combined with the treatment's safety and ease of administration, supports further multicentre evaluation of antisecretory factor as a potential therapy for severe traumatic brain injury.