BLOC-ICH: Interleukin-1 Receptor Antagonist in Intracerebral Haemorrhage

• Status: Completed
• Trial end date: 2021-04-30
• Target enrollment: 0
• Participant gender: All

Summary

This trial will help inform the development of a new treatment for intracerebral haemorrhage (ICH; also known as haemorrhagic stroke). ICH is a type of stroke caused by spontaneous bleeding into the brain. In the hours to days after bleeding occurs, inflammation develops in the brain around the haematoma (collection of blood in the brain). Inflammation is the body's natural response to injury, however when it continues unchecked there is a risk that the brain tissue around the haematoma will become swollen. This type of swelling can worsen existing stroke symptoms or cause new deficits such as speech disturbance and limb weakness, which can lead to long term disability.

The level of inflammation in the blood is high after ICH. The investigators want to investigate whether blocking this inflammation can improve overall recovery. The investigators research group has extensively investigated the use of a well-established anti-inflammatory drug, Kineret® in trials with patients who have suffered a stroke or brain haemorrhage. Kineret® is similar to a naturally-produced protein called interleukin-1 receptor antagonist (IL-1Ra) and is already licensed to treat patients with rheumatoid arthritis. The investigators have evidence from these previous studies that Kineret® reduced levels of inflammation in the blood after ischaemic stroke (caused by a blockage in an artery). However, in order to develop Kineret® as a treatment for ICH, the investigators need to know if it reduces levels of inflammation present in the blood following ICH and if it reduces swelling in the brain.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Adrian Parry-Jones
• Collaborators: Manchester University NHS Foundation Trust; National Institute for Health Research, United Kingdom; Salford Royal NHS Foundation Trust
• Treatments: Interleukin 1 Receptor Antagonist Protein

Criteria

Inclusion Criteria:

1. Patients with spontaneous, non-traumatic, supratentorial ICH with no underlying macrovascular or neoplastic cause admitted to a participating centre within 8 hours of symptom onset.

2. No concomitant health problems that, in the opinion of the principle Investigator (PI) or designee, would interfere with participation, administration of study drug or assessment of outcomes including safety.

3. Willing and able to give informed consent or consent available from a patient representative for trial inclusion including agreement in principle to receive study drug and undergo all study assessments.

4. Male or female aged 18 years or above.

Exclusion Criteria:

1. Severe ICH, unlikely to survive to 72 hours scan, in the opinion of the treating clinician. For example, a GCS score < 6 at time of consent);

2. Confirmed or suspected structural abnormality as cause of ICH (including tumour, vascular malformation).

3. Confirmed or suspected haemorrhagic transformation of an arterial or venous infarct.

4. Acute neurosurgery planned within 72 hours of admission.

5. Known active tuberculosis or active hepatitis.

6. Known active malignancy.

7. Neutropenia (absolute neutrophil count (ANC) <1.5 x10^9/L).

8. Abnormal renal function (creatinine clearance or estimated Glomerular Filtration Rate (eGFR) < 30 ml/minute) documented in the last 3 months prior to this ICH.

9. Live vaccinations within the last 10 days prior to this ICH.

10. Previous or concurrent treatment with IL-1Ra known at the time of trial entry or previous participation in this trial.

11. Previous or current treatment with etanercept or any other tumour necrosis factor alpha (TNFα) antagonist.

12. Known to have participated in a clinical trial of an investigational agent or device in the 30 days prior to symptom onset.

13. Known to have participated in a clinical trial of an investigational agent or device within 5 half-lives (of the previous agent or device) prior to symptom onset.

14. Known to be pregnant or breast-feeding or inability to reliably confirm that the patient is not pregnant.

15. Known diagnosis of Still's disease.

16. Clinically significant serious concurrent medical condition, premorbid illnesses, or concurrent serious infection, at the PI's (or designee's) discretion, which could affect the safety or tolerability of the intervention.

17. Known allergy to IL-1Ra or any of the excipients listed in the drug summary of product characteristics (SmPC).

18. Known allergy to other products that are produced by DNA technology using the micro-organism E. coli (e.g. E.coli derived protein).