Subarachnoid Hemorrhage
Conditions
Keywords
Aneurysmal
Brief summary
This phase III trial will establish whether IL-1Ra, with sub-cutaneous (SC) administration twice daily for up to 21 days post aneurysmal subarachnoid haemorrhage (aSAH), improves clinical outcome as measured by ordinal shift in mRS at 6 months. Patients with SAH transferred to a neurosurgical centre will be identified and approached for study participation. Following consent, patients will be randomised to receive either IL-1Ra or placebo for a maximum of 21 days from onset of symptoms. Patients who are found to be non-aneurysmal following randomisation will be withdrawn from the study treatment. Blood samples for plasma IL-6 will be obtained prior to randomisation and at day 3-5 post randomisation for IL-6 & IL-1 measurement. Safety will be measured at 30 days post randomisation and outcome assessed at 6 months post randomisation.
Interventions
DRUGIL-1Ra
Doses to be administered subcutaneously (SC) twice daily (12 hourly) starting within 72 hours of ictus (onset of symptoms) for a maximum of 21 days from ictus (or sooner if discharged from neurosurgical centre).
DRUGIL-1Ra Placebo
Doses to be administered subcutaneously (SC) twice daily (12 hourly) starting within 72 hours of ictus (onset of symptoms) for a maximum of 21 days from ictus (or sooner if discharged from neurosurgical centre).
Sponsors
National Institute for Health Research, United Kingdom
Clinical Trials Unit, Manchester
Northern Care Alliance NHS Foundation Trust
University of Manchester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with CT positive spontaneous SAH admitted to a participating neurosurgical centre where written informed consent can be obtained and study drug can be administered within 72 hours of ictus. 2. No concomitant health problems that, in the opinion of the 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. Unconfirmed or uncertain diagnosis of spontaneous SAH. 2. Known active tuberculosis or active hepatitis. 3. Known active malignancy. 4. Known Still's Disease 5. Neutropenia (ANC \<1.5 x 109/L ). 6. Abnormal renal function (creatinine clearance or estimated Glomerular Filtration Rate (eGFR) \< 30 ml/minute) documented in the last 3 months prior to this SAH. 7. Live vaccinations within the last 10 days of this SAH. 8. Previous or concurrent treatment with IL-1Ra known at the time of trial entry or previous participation in this trial. 9. Current treatment with TNF antagonists. 10. Known to have participated in a clinical trial of an investigational agent or device in the 30 days prior to ictus. 11. 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 ictus. 12. Known to be pregnant or breast feeding or inability to reliably confirm that the patient is not pregnant 13. Clinically significant serious concurrent medical condition, pre morbid illnesses, or concurrent serious infection, at the PI's (or designee's) discretion, which could affect the safety or tolerability of the intervention. 14. Known allergy to IL-1Ra or any of the excipients listed in the drug SmPC 15. Known allergy to other products that are produced by DNA technology using the micro-organism E. coli (e.g. E.coli derived protein). 16. Current treatment with IL-6 or IL-1 inhibitors or drugs affecting the IL-1 axis. 17. History of DRESS syndrome.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ordinal shift in modified Rankin Score (mRS) | 6 months post randomisation |
Secondary
| Measure | Time frame |
|---|---|
| Measurement of mood using HADS | 6 months post randomisation |
| Measurement of fatigue using Fatigue score | 6 months post randomisation |
| Measurement of quality of life using EQ-5D-5L score | 6 months post randomisation |
Countries
United Kingdom
Outcome results
None listed