Design Multicentre, prospective, randomized, three-armed (1:1:1) trial with open label treatment and blinded end-point assessment (PROBE).
Population 75 patients with supratentorial spontaneous intracranial haemorrhage that can start treatment within 8 hours after symptom onset will be included over the course of 2 years in 3 different hospitals.
Inclusion criteria
1. Age ≥ 18 years;
2. Supratentorial non-traumatic intracerebral haemorrhage on CT, without a causative lesion on CT-angiography;
3. Minimal intracerebral haemorrhage volume of 10 mL;
4. Intervention can be started within 8 hours from symptoms onset;
5. Patient’s or legal representative’s informed consent.
Exclusion criteria
1. Severe ICH, unlikely to survive the first 72 hours (GCS < 6);
2. (Suspected) haemorrhagic transformation of an a infarct;
3. Planned neurosurgical haematoma evacuation;
4. Severe infection at admission, requiring antibiotic treatment;
5. Known active tuberculosis or active hepatitis;
6. Use of immunosuppressive or immune-modulating therapy;
7. Neutropenia (ANC <1.5 x 109/L );
8. Pre-stroke mRS score ≥ 3;
9. Pregnancy or breast-feeding;
10. Standard contraindications to MRI;
11. Known prior allergic reaction to gadolinium contrast or one of the constituents of its solution for administration;
12. Known allergy to anakinra or other products that are produced by DNA technology using the micro-organism E. coli;
13. Vaccinations with live attenuated microorganisms within the last 10 days;
14. Severe renal impairment (eGFR <30ml/min/1.73m);
15. Known active malignancy.
Intervention Patients will receive anakinra in either a high dose (loading dose 500mg i.v., followed by infusion with 2mg/kg/h over 3 days) or in a low dose (loading dose 100mg s.c., followed by subcutaneous administration of 100mg twice a day for 3 days), started within 8 hours of symptom onset. The control group will receive standard medical management.
Outcomes Primary outcome is perihaematomal oedema, measured as oedema extension distance on MRI at day 7±1. Secondary outcomes include the safety profile of anakinra in patients with ICH, and the effect of anakinra on serum inflammation markers, MRI measures of blood brain barrier integrity and functional outcome at 90±7 days.
Study procedures The schematic overview of the study procedures is provided below:
Study protocol The complete study protocol can be found here: