NCT04834388

Studying Anakinra to Reduce Secondary Brain Damage After Spontaneous Haemorrhagic Stroke

Anakinra in Cerebral Haemorrhage to Target Secondary Injury Resulting From Neuroinflammation - a Phase II Clinical Trial

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 75 (estimated)
• Sponsor: Radboud University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial\] is to determine if anakinra can ameliorate the formation of perihaematomal oedema in patients with spontaneous intracerebral haemorrhage (ICH). The main aims are: * To determine the effect of high-dose versus low-dose anakinra compared to standard medical management on perihaematomal oedema formation in the first week after ICH. * Determine the safety profile of anakinra in these patients * Study the effect of anakinra treatment on inflammation markers, blood-brain-barrier permeability and functional outcome. Researchers will compare treatment with anakinra for three days, in either a low or high dose, with standard medical care after ICH. Participants will: * Be randomized to receive anakinra during three days, or receive standard medical care * Undergo a MRI scan seven days after their ICH * Take part in a telephone interview their functional performance three months later.

Detailed description

Spontaneous intracerebral haemorrhage (sICH) is the deadliest stroke subtype yearly affecting over 6000 patients in the Netherlands. Treatment options are very limited. Inflammation plays a vital role in the development of sICH-related secondary brain injury (SBI). Within 4 hours after sICH onset, blood components and thrombin induce the release of cytokines and other inflammatory molecules, with subsequent microglial activation, blood brain barrier (BBB) damage and the formation of perihaematomal oedema (PHO). Among the released cytokines, interleukin 1 beta (IL-1β) has a pivotal role. Recombinant human interleukin-1 receptor antagonist (IL-1Ra, anakinra) effectively antagonizes IL-1β through competitive binding to the IL-1 receptor. Anakinra is available for treatment of rheumatoid arthritis, other inflammatory diseases and has been studied in acute sepsis. We hypothesize that anakinra safely reduces SBI after sICH, and that its effect is dose-dependent. Objective: To determine the effect of high-dose versus low-dose anakinra compared to standard medical management on oedema extension distance (OED) determined with MRI on day 7±1. Second, to study the safety profile of anakinra. Furthermore, to assess its effect on 1) serum inflammatory markers IL-1β, IL-6, hsCRP, neutrophil and total white blood cell counts at day 1, 3 and 7 compared to baseline; 2) dynamic contrast enhanced (DCE-) MRI measurement of BBB transfer constant (Ktrans) on day 7±1, and; 3) to estimate an effect on functional outcome in patients with sICH. Study design: Multicentre, prospective, randomized, three-armed (1:1:1) trial with open label treatment and blinded end-point assessment (PROBE design) . Study population: 75 patients with supratentorial sICH admitted within 8 hours after symptom onset. 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; n=25) or in a low dose (loading dose 100mg s.c.., followed by subcutaneous administration of 100mg twice a day for 3 days; n=25), started within 8 hours of symptom onset. The control group (n=25) will receive standard medical management. Main study parameters/endpoints: Primary objective is to test whether anakinra reduces subacute perihaematomal oedema after sICH, measured as OED on MRI at day 7±1.

Conditions

• Intracerebral Hemorrhage

Interventions

Type	Name	Description
DRUG	Anakinra	Anakinra treatment is started within 8 hours of symptom onset

Timeline

• Start date: 2022-08-10
• Primary completion: 2025-09-01
• Completion: 2025-12-01
• First posted: 2021-04-08
• Last updated: 2024-11-18

Locations

1 site across 1 country: Netherlands