NCT03249207

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 Patients who are found to be non-aneurysmal following randomisation will be withdrawn from the study treatment.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

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
612

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Oct 2018

Longer than P75 for phase_3

Geographic Reach
1 country

17 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 9, 2017

Completed
6 days until next milestone

First Posted

Study publicly available on registry

August 15, 2017

Completed
1.2 years until next milestone

Study Start

First participant enrolled

October 11, 2018

Completed
5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2024

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2024

Completed
Last Updated

November 21, 2023

Status Verified

October 1, 2023

Enrollment Period

5.5 years

First QC Date

August 9, 2017

Last Update Submit

November 17, 2023

Conditions

Keywords

Aneurysmal

Outcome Measures

Primary Outcomes (1)

  • Ordinal shift in modified Rankin Score (mRS)

    6 months post randomisation

Secondary Outcomes (3)

  • 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

Study Arms (2)

IL-1Ra twice daily

ACTIVE COMPARATOR
Drug: IL-1Ra

Placebo twice daily

PLACEBO COMPARATOR
Drug: IL-1Ra Placebo

Interventions

IL-1RaDRUG

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).

IL-1Ra twice daily

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).

Placebo twice daily

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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.
  • Male or female aged 18 years or above.

You may not qualify if:

  • Unconfirmed or uncertain diagnosis of spontaneous SAH.
  • Known active tuberculosis or active hepatitis.
  • Known active malignancy.
  • Known Still's Disease
  • Neutropenia (ANC \<1.5 x 109/L ).
  • Abnormal renal function (creatinine clearance or estimated Glomerular Filtration Rate (eGFR) \< 30 ml/minute) documented in the last 3 months prior to this SAH.
  • Live vaccinations within the last 10 days of this SAH.
  • Previous or concurrent treatment with IL-1Ra known at the time of trial entry or previous participation in this trial.
  • Current treatment with TNF antagonists.
  • Known to have participated in a clinical trial of an investigational agent or device in the 30 days prior to ictus.
  • 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.
  • Known to be pregnant or breast feeding or inability to reliably confirm that the patient is not pregnant
  • 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.
  • Known allergy to IL-1Ra or any of the excipients listed in the drug SmPC
  • Known allergy to other products that are produced by DNA technology using the micro-organism E. coli (e.g. E.coli derived protein).
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

Derriford Hospital

Plymouth, Devon, PL6 8DH, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, South Yorkshire, S10 2JF, United Kingdom

Location

University Hospital of Wales

Cardiff, Wales, CF14 4XW, United Kingdom

Location

Leeds General Infirmary

Leeds, Yorkshire, LS1 3EX, United Kingdom

Location

Royal Sussex County Hospital

Brighton, BN2 5BE, United Kingdom

Location

Southmead Hospital

Bristol, BS10 5NB, United Kingdom

Location

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

The Walton Centre

Liverpool, L9 7LJ, United Kingdom

Location

Royal London Hospital

London, E1 1FR, United Kingdom

Location

St George's Hospital

London, SW17 0QT, United Kingdom

Location

Charing Cross Hospital

London, W6 8RF, United Kingdom

Location

National Hospital for Neurology and Neurosurgery, Queen Square

London, WC1N 3BG, United Kingdom

Location

Northern Care Alliance NHS Foundation Trust

Manchester, United Kingdom

Location

Queens Medical Centre

Nottingham, NG7 2UH, United Kingdom

Location

Royal Preston Hospital

Preston, PR2 9HT, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Royal Stoke University Hospital

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Intracranial HemorrhagesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesHemorrhagePathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

CytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological Factors

Study Officials

  • Andrew King

    University of Manchester

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 9, 2017

First Posted

August 15, 2017

Study Start

October 11, 2018

Primary Completion

April 1, 2024

Study Completion

September 1, 2024

Last Updated

November 21, 2023

Record last verified: 2023-10

Locations