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

NCT03737344 | Completed Phase 2 DMC

• 1 other identifier: R118439
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Intracerebral Haemorrhage

Keywords

haemorrhage; Stroke; Bleeding

Outcome Measures

Primary Outcomes (1)

• Oedema extension distance (OED)

  Perihaematomal OED on CT scan at 72 hours (+/-12 hours), which equates to the average distance that oedema extends beyond the haematoma border.

  72 hours (+/-12 hours) post symptoms onset

Secondary Outcomes (9)

• Early haematoma growth

  between baseline and 72 hours post symptoms onset

• Early Neurological Decline (END)

  between baseline and 72 hours post symptoms onset

• Inflammatory markers

  from day 0 (baseline) to day 4 post randomisation

• Quantitative blood-brain barrier permeability

  day 2-4 post randomisation

• modified Rankin Score (mRS)

  3 months post randomisation

Study Arms (2)

IL-1Ra Kineret®

ACTIVE COMPARATOR

100mg doses of the trial drug Kineret® will be administered subcutaneously (SC) twice daily (12 hourly) starting within 8 hours of symptoms onset for a maximum of 3 days from symptoms onset (or sooner if discharged from neurosurgical centre).

Drug: IL-1Ra Kineret®

IL-1Ra Placebo

PLACEBO COMPARATOR

100mg doses of the placebo will be administered subcutaneously (SC) twice daily (12 hourly) starting within 8 hours of symptoms onset for a maximum of 3 days from symptoms onset (or sooner if discharged from neurosurgical centre).

Other: IL-1Ra Placebo

Interventions

IL-1Ra Kineret® DRUG

Kineret® 100 mg in 0.67 ml Prefilled Syringe

Also known as: Anakinra

IL-1Ra Kineret®

IL-1Ra Placebo OTHER

Placebo identical to Kineret® 100 mg in 0.67 ml Prefilled Syringe

IL-1Ra Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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);
• Confirmed or suspected structural abnormality as cause of ICH (including tumour, vascular malformation).
• Confirmed or suspected haemorrhagic transformation of an arterial or venous infarct.
• Acute neurosurgery planned within 72 hours of admission.
• Known active tuberculosis or active hepatitis.
• Known active malignancy.
• Neutropenia (absolute neutrophil count (ANC) \<1.5 x10\^9/L).
• Abnormal renal function (creatinine clearance or estimated Glomerular Filtration Rate (eGFR) \< 30 ml/minute) documented in the last 3 months prior to this ICH.
• Live vaccinations within the last 10 days prior to this ICH.
• Previous or concurrent treatment with IL-1Ra known at the time of trial entry or previous participation in this trial.
• Previous or current treatment with etanercept or any other tumour necrosis factor alpha (TNFα) antagonist.
• Known to have participated in a clinical trial of an investigational agent or device in the 30 days prior to symptom onset.
• 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.
• Known to be pregnant or breast-feeding or inability to reliably confirm that the patient is not pregnant.
• Known diagnosis of Still's disease.

Sponsors & Collaborators

• Adrian Parry-Jones: lead
• Northern Care Alliance NHS Foundation Trust: collaborator
• National Institute for Health Research, United Kingdom: collaborator
• Manchester University NHS Foundation Trust: collaborator

Study Sites (1)

Salford Royal NHS Foundation Trust

Manchester, North West, M6 8HD, United Kingdom

Location

Related Publications (1)

• Parry-Jones AR, Stocking K, MacLeod MJ, Clarke B, Werring DJ, Muir KW, Vail A. Phase II randomised, placebo-controlled, clinical trial of interleukin-1 receptor antagonist in intracerebral haemorrhage: BLOcking the Cytokine IL-1 in ICH (BLOC-ICH). Eur Stroke J. 2023 Sep;8(3):819-827. doi: 10.1177/23969873231185208. Epub 2023 Jul 15.

  PMID: 37452707 DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage; Hemorrhage; Stroke

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Adrian Parry-Jones, PhD, MRCP

  University of Manchester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: NIHR Clinician Scientist & Honorary Consultant Neurologist

Study Record Dates

• First Submitted: October 18, 2018
• First Posted: November 9, 2018
• Study Start: May 17, 2019
• Primary Completion: February 19, 2021
• Study Completion: April 30, 2021
• Last Updated: October 5, 2021

Record last verified: 2021-10

Locations

GB (1)