TITAN-TBI

Targeted Interleukin-6 Therapy Against Neuroinflammation

A trial of tocilizumab, an anti-inflammatory medication, to understand how controlling inflammation in the whole body can prevent inflammation damage to the brain following head injury.

Research summary

Too much inflammation in the brain is thought to worsen recovery after a head injury, and we think that reducing inflammation might improve patients' outcomes. This study is looking to understand whether treatment with an anti-inflammatory medicine (Tocilizumab) might be helpful after head injury. Tocilizumab is commonly used in other illnesses such  as rheumatoid arthritis and more recently it has been shown to be effective in treating severe COVID-19.

This study will recruit a total of 60 participants, over two stages, who have suffered a head injury that means they have had to go to intensive care and have a drain in their brain that measures brain inflammation.

In the first stage, participants will receive either a single dose of Tocilizumab or the normal care given to patients with head injury. In the second stage, participants will randomly (i.e. by chance) be allocated to receive a single dose of either Tocilizumab or a salt water placebo, alongside the usual care given to patients with head injury. In both stages, participants will be followed up for 6 months.

As this is the first study looking at Tocilizumab in head injury, we are focussing on whether it reduces inflammation in the brain and whether we can detect a beneficial effect via blood samples. If the study is successful, we will plan to undertake a larger study to investigate definitely whether it improves recovery from head injury.

Main inclusion criteria

  • Have had Legal Representative consent given;
  • Be aged 18 years or older;
  • Have moderate to severe TBI (Glasgow Coma Scale (GCS)<13);
  • Have an external ventricular drain (EVD) sited for clinical care (work package 1 only);
  • Have a cerebral microdialysis (CMD) catheter in situ (or plan to site within the requisite timeframe) (work package 2 only).

Main exclusion criteria

  • Brain-injury or co-morbidity deemed incompatible with survival;
  • Timing of injury such that it is clear IMP/placebo could not be delivered within 48 hours (e.g. delayed secondary transfer from peripheral hospital; work package 2 only)
  • Known allergy to tocilizumab or any of its excipients;
  • Contraindications of the IMP as listed in the Summary of Product Characteristics (SmPC);
  • Weight<50 kg;
  • Active severe infection;
  • Perforated viscus on cross-sectional imaging;
  • Neutropoenia<1x109/litre at screening;
  • Actively taking immunosuppression medications (e.g. immunotherapy) or known immunodeficiency disorder (n.b. adequately treated HIV ≠ exclusion criterion);
  • Pregnant or breast-feeding;
  • Received tocilizumab within 30 days prior to the screening visit; or
  • Prior receipt of any other investigational medicinal product, or participation in another interventional clinical trial, within 30 days or 5 half-lives after the last IMP dose (whichever is longer) before the first dose of study treatment;
  • Use of medication metabolised by CYP450 3A4, 1A2 or 2C9 which in the opinion of the investigator will put the participant at risk if the drug level would significantly decrease for a period of time following a single dose of tocilizumab;
  • Any other significant disease, disability or investigation result which, in the opinion of the Investigator, may either put the participants at risk, or may influence the result of the trial, or the participant's ability to participate in the trial.

Chief investigator

Chief Investigator: Dr Edward Needham

Contact details

Clinical Trials Coordinator: Bronwen Harry, George Pettitt

Email: [email protected]