Clinical trial NCT03249207: SC IL-1Ra in SAH - Phase III Trial (SCIL)
Official title: Does Interleukin-1 Receptor Antagonist Improve Outcome Following Aneurysmal Subarachnoid Haemorrhage (aSAH)? A Phase III Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Subarachnoid Hemorrhage
Keywords: Aneurysmal
Lead sponsor: University of Manchester
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
name: Clinical Trials Unit, Manchester
name: Northern Care Alliance NHS Foundation Trust
First posted: 2017-08-15
Enrollment: 612
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 Patients who are found to be non-aneurysmal following randomisation will be withdrawn from the study treatment.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.


Eligibility criteria: 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.

Primary outcomes:
measure: Ordinal shift in modified Rankin Score (mRS)
timeFrame: 6 months post randomisation
Secondary outcomes:
measure: Measurement of mood using HADS
timeFrame: 6 months post randomisation
measure: Measurement of fatigue using Fatigue score
timeFrame: 6 months post randomisation
measure: Measurement of quality of life using EQ-5D-5L score
timeFrame: 6 months post randomisation
Other outcomes:
Locations:
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: Devon
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
state: South Yorkshire
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
state: Yorkshire
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
city: Bristol
country: United Kingdom
facility: Southmead Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Liverpool
country: United Kingdom
facility: The Walton Centre
city: London
country: United Kingdom
facility: Royal London Hospital
city: London
country: United Kingdom
facility: St George's Hospital
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: London
country: United Kingdom
facility: National Hospital for Neurology and Neurosurgery, Queen Square
city: Manchester
country: United Kingdom
facility: Northern Care Alliance NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Queens Medical Centre
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Stoke-on-Trent
country: United Kingdom
facility: Royal Stoke University Hospital
Study officials:
affiliation: University of Manchester
name: Andrew King
role: PRINCIPAL_INVESTIGATOR
References: