A trial to test tocilizumab, an anti-inflammatory medication, in understanding how controlling the whole body's inflammation can prevent inflammation damage to the brain following head injury
| ISRCTN | ISRCTN16877626 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16877626 |
| Integrated Research Application System (IRAS) | 1009886 |
| Sponsor's protocol code number | CCTU0447 |
| Sponsors | Cambridge University Hospitals NHS Foundation Trust, University of Cambridge |
| Funder | Medical Research Council |
- Submission date
- 09/01/2026
- Registration date
- 17/03/2026
- Last edited
- 23/03/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Injury, Occupational Diseases, Poisoning
Plain English summary of protocol
Background and study aims
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 a 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. As this is the first study looking at tocilizumab in head injury, it focuses on whether it reduces inflammation in the brain and whether it can be detected in blood samples. If the study is successful, a larger study is planned to investigate definitively whether it improves recovery from head injury.
Who can participate?
Patients at Cambridge University Hospitals NHS Foundation Trust 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
What does the study involve?
Participants will be involved in two working packages that will run in parallel (with 10 participants recruited into work package 1, and 50 participants recruited into work package 2). If recruited to work package 1, participants will receive either a single dose of tocilizumab or the normal care given to patients with head injury. If recruited to work package 2, participants will randomly (i.e. by chance) be allocated to receive a single dose of either tocilizumab or a saltwater placebo, alongside the usual care given to patients with head injury. For work package 2, the first 14 participants will be recruited to the open-label portion of the work package (where treatment allocation will be known), after which the following 36 participants will be recruited to the double-blind portion of the work package (where participants are randomly assigned placebo or tocilizumab treatment). In both stages, participants will be followed up for 6 months.
What are the possible benefits and risks of participating?
Current treatment for traumatic brain injury focuses on maintaining the body's normal functions. There is currently no direct treatment for traumatic brain injury. There is no guarantee that a participant will benefit from taking part in this trial, however this trail aims to see whether tocilizumab reduces inflammation in the brain and whether we can detect a beneficial effect via blood samples. Additionally, information collected from participants in this trial may benefit participants with head injuries in the future.
TOCILIZUMAB
As with all medications, tocilizumab has the potential to cause side effects. The most common (occurring in more than 5% of people) side effects include upper respiratory tract infections, nasopharyngitis, headache, hypertension and increased alanine transaminase. As the majority of patients who require intensive care treatment develop nosocomial infections, infection is an expected adverse event for participants in this trial. As an immunosuppressive agent, tocilizumab poses the risk of increasing the severity or duration of an infection and therefore, participants with active, severe infections will be excluded from the trial.
Due to the mechanism of action of tocilizumab, abnormal blood results are an anticipated effect which will be monitored through regular blood tests. Additionally, hypersensitivity to tocilizumab or any of its excipients is an exclusion criterion.
The effects of tocilizumab on pregnancy and the developing foetus are not yet known or fully understood.
BLOOD TESTS
Blood sampling will be via arterial or central venous lines placed as part of standard care during the admission period for participants in the ICU stratum. Participants attending for follow-up will need to undergo a blood draw and may experience the discomfort associated with a needle stick, and may suffer bruising at the site of the needle stick. This will be minimized as much as possible, and only personnel trained in venepuncture will perform this task, and no more than two venepuncture attempts will take place. Whenever possible, blood draws will be combined with those of routine clinical care.
TIME COMMITMENT
There is a substantial time commitment associated with being part of a trial. The number of visits has been minimised as much as possible to help with this.
INCIDENTAL FINDINGS
There is a chance that trial assessments may discover something about the participant's health that they or their Personal Legal Representative are unaware of. In such circumstances, we would discuss the findings with the participant/ Personal Legal Representative as appropriate and inform their GP. If referral to another specialist was required, we would arrange this, in consultation with their GP, if that is what they would like. Such early detection of new medical issues has the benefit of starting treatment early, but, in a small number of cases, may have implications for future employment and insurance.
CONSENT MODEL
Patients will not have the capacity to consent prior to enrolment, with consent being given by the legal representative (personal or professional), which takes place over a short timeframe. Once a patient regains capacity, they will then be approached for their consent, which is after they have already enrolled and received the trial medication. This, therefore, has the potential to cause distress to the patient. To mitigate this risk, consent activities will be undertaken by appropriate staff members with knowledge and training in this consent model.
All risks are outlined in the consultee and participant information sheet and discussed with the consultee and, where possible, the participant as part of the consent process.
Where is the study run from?
Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, UK
When is the study starting and how long is it expected to run for?
March 2026 to September 2029
Who is funding the study?
Medical Research Council, UK
Who is the main contact?
cuh.neurosciencecctu@nhs.net
Contact information
Scientific, Public
CCTU, Box 401. CUH NHS Foundation Trust, Addenbrookes Hospital, Level 6, Coton House, Hills Road
Cambridge
CB2 0QQ
United Kingdom
| Phone | +44 (0)1223 348498 |
|---|---|
| cuh.neurosciencecctu@nhs.net |
Principal investigator
John van Geest Centre for Brain Repair, E D Adrian Building, Forvie Site, Cambridge CB2 0PY
Cambridge
CB2 0PY
United Kingdom
| Phone | +44 (0)1223 767069 |
|---|---|
| edneedham@doctors.org.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Allocation | Randomized controlled trial |
| Masking | Blinded (masking used) |
| Control | Placebo |
| Assignment | Parallel |
| Purpose | Treatment |
| Scientific title | Modulating interleukin-6 pathways to understand the effect of systemic inflammation on detrimental neuroinflammation following traumatic brain injury |
| Study acronym | TITAN-TBI |
| Study objectives | The main objective of Work Package 1 (WP1) (n = 10) is to assess the pharmacokinetics of tocilizumab in people with traumatic brain injury (TBI). The main objective of Work Package 2 (WP2) (n = 50) is to assess the impact of tocilizumab treatment on neuroinflammation in people with TBI. The secondary objectives for WP1 are as follows: 1. To assess the impact of tocilizumab treatment on systemic inflammation in people with TBI 2. To assess the relationships between inflammatory mediators measured in cerebrospinal fluid (CSF) and those measured by cerebral microdialysis (CMD) catheters 3. To establish the feasibility of treating with a monoclonal antibody in the hyperacute phase of TBI within a clinical trial 4. To assess the safety of tocilizumab in people with TBI The secondary objectives for WP2 are as follows: 1. To assess the impact of tocilizumab treatment on systemic inflammation in people with TBI 2. To evaluate whether tocilizumab reduces biomarkers of brain injury 3. To assess the safety of tocilizumab in people with TBI |
| Ethics approval(s) |
Submitted 09/01/2026, East of England – Essex REC (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; -; essex.rec@hra.nhs.uk), ref: 26/EE/0024 |
| Health condition(s) or problem(s) studied | Traumatic brain injury |
| Intervention | WP1: 10 participants will be recruited to an open-label, non-randomised portion of the trial. 1. Treatment arm: The first 5 participants enrolled into WP1 will receive a single dose of tocilizumab, in addition to standard of care. The dose is based on weight (>40 and ≤65 kg 400 mg, >65 and ≤90 kg 600 mg, >90 kg 800 mg) and will be intravenously administered once at the end of the baseline visit only. 2. WP1 Control arm: After the first 5 participants of WP1 have received tocilizumab, the final 5 participants for WP1 will receive standard of care. WP2: 50 participants will be recruited to a randomised portion of the trial, where the intervention is determined randomly (i.e., by chance). For the first 14 participants recruited to WP2, treatment will be “open label”, meaning the participant and research team will know what treatment has been allocated. For the remaining participants (participants 15-50), treatment allocation will not be known by the participant or research team (double-blind). Randomisation allocations will be performed by Sealed Envelope. 1. Treatment arm: Participants will receive a single dose of tocilizumab, in addition to standard of care. The dose is based on weight (>40 and ≤65 kg 400 mg, >65 and ≤90 kg 600 mg, >90 kg 800 mg) and will be intravenously administered once at the end of the baseline visit only. 2. WP2 Control arm: Participants will receive a single dose of 100 ml 0.9% saline, in addition to standard of care, which will be intravenously administered once at the end of the baseline visit only. |
| Intervention type | Drug |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Tocilizumab |
| Primary outcome measure(s) |
|
| Key secondary outcome measure(s) |
|
| Completion date | 30/09/2029 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 110 Years |
| Sex | All |
| Target sample size at registration | 60 |
| Key inclusion criteria | The main inclusion criteria for both WPs are as follows: 1. Have had Legal Representative consent given 2. Be aged 18 years or older 3. Have moderate to severe post-resuscitation TBI (Glasgow Coma Scale (GCS) <13) Additional inclusion criteria for WP1 are: 1. Have an external ventricular drain (EVD) and a catheter sited for clinical care Additional inclusion criteria for WP2 are: 1. Have a CMD catheter in situ (or plan to site within the requisite timeframe for investigational medicinal product administration i.e. 48 hours post-injury) |
| Key exclusion criteria | Current exclusion criteria as of 23/03/2026: The main exclusion criteria for both WPs are as follows: 1. Brain injury or comorbidity deemed incompatible with survival 2. 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; WP2 only) 3. Known allergy to tocilizumab or any of its excipients 4. Contraindications of the IMP as listed in the Summary of Product Characteristics (SmPC) 5. Weight <50 kg 6. Active severe infection 7. Perforated viscus on cross-sectional imaging 8. Neutropoenia <1 x 10⁹/litre at screening 9. Alanine aminotransferase (ALT) > 5x upper limit of normal at screening 10. Thrombocytopoenia <50 x 10³ / microlitre at screening 11. Actively taking immunosuppression medications (e.g. immunotherapy) or known immunodeficiency disorder (n.b. adequately treated HIV ≠ exclusion criterion) 12. Pregnant or breastfeeding 13. Received tocilizumab within 30 days prior to the screening visits 14. 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 15. 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 16. Any other significant disease, disability or investigation result which, in the opinion of the Investigator, may either put the participant at risk, or may influence the result of the trial, or the participant’s ability to participate in the trial Previous exclusion criteria: The main exclusion criteria for both WPs are as follows: 1. Brain injury or comorbidity deemed incompatible with survival 2. 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; WP2 Only) 3. Known allergy to tocilizumab or any of its excipients 4. Weight ≤40 kg 5. Contraindications of the IMP as listed in the Summary of Product Characteristics (SmPC) 6. Active severe infection 7. Perforated viscus on cross-sectional imaging 8. Neutropoenia <1 x 10⁹/litre at screening 9. Alanine aminotransferase (ALT) > 10x upper limit of normal at screening 10. Thrombocytopoenia <50 x 10³ / microlitre at screening 11. Actively taking immunosuppression medications (e.g. immunotherapy) or known immunodeficiency disorder (N.B. adequately treated HIV ≠ exclusion criterion) 12. Pregnant or breastfeeding 13. Received tocilizumab or any other investigational drug within 30 days prior to the screening visit 14. 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 15. Any other significant disease, disability or investigation result which, in the opinion of the Investigator, may either put the participant at risk, or may influence the result of the trial, or the participant’s ability to participate in the trial |
| Date of first enrolment | 01/03/2026 |
| Date of final enrolment | 31/12/2028 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Cambridge
CB2 0QQ
England
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be stored in a non-publicly available repository |
Editorial Notes
23/03/2026: The exclusion criteria were updated.
17/03/2026: ISRCTN received notification of combined HRA/MHRA approval for this trial on 17/03/2026.
09/01/2026: Study's existence confirmed by Health Research Authority (HRA) (UK)
