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Intracerebral HemorrhagePhase 2ACTIONNCT04834388

Studying Anakinra to Reduce Secondary Brain Damage After Spontaneous Haemorrhagic Stroke

A Phase 2 study testing Anakinra in people with Intracerebral Hemorrhage, run by Radboud University Medical Center at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Intracerebral Hemorrhage
What is being tested?
Anakinra
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
1 siteNetherlands
Study dates
10 Aug 2022to Dec 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18 years;
  • Supratentorial non-traumatic ICH confirmed by CT, without a confirmed causative lesion on admission CT-angiography (e.g. aneurysm, AVM, DAVF, cerebral venous sinus thrombosis) or other known underlying lesion (e.g. tumour, cavernoma);
  • Minimal intracerebral haemorrhage volume of 10 mL;
  • Intervention can be started within 8 hours from symptoms onset;
  • Patient's or legal representative's informed consent.

Who cannot join

  • Severe ICH, unlikely to survive the first 72 hours (defined as Glasgow Coma Scale score < 6 at time of consent);
  • Confirmed or suspected haemorrhagic transformation of an arterial or venous infarct;
  • Planned neurosurgical haematoma evacuation;
  • Severe infection at admission, requiring antibiotic treatment;
  • Known active tuberculosis or active hepatitis;
  • Use of immunosuppressive or immune-modulating therapy at admission (see 15.1 Appendix A);
Show all 15Show fewer
  • Neutropenia (Absolute Neutrophil Count (ANC) <1.5 x 109/L );
  • Pre-stroke modified Rankin Scale score ≥ 3;
  • Pregnancy or breast-feeding;
  • Standard contraindications to MRI (see 15.2 Appendix B);
  • Known prior allergic reaction to gadolinium contrast or one of the constituents of its solution for administration;
  • Known allergy to anakinra or other products that are produced by DNA technology using the micro-organism E. coli;
  • Live vaccinations within the last 10 days prior to this ICH;
  • Severe renal impairment (eGFR <30ml/min/1.73m)
  • Active malignancy

Trial locations and contacts

1 site in 1 country.

Floris H.B.M Schreuder, MD PhD contact

+31650155755

floris.schreuder@radboudumc.nl

Maaike P. Cliteur, MD contact

+31650155723

maaike.cliteur@radboudumc.nl

Netherlands1 site, 1 recruiting

  • Radboudumc

    Nijmegen

    Radboudumc

    Recruiting

Other trials in Netherlands

About this study

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

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.
Read more

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.
Read the 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.

Being tested
Anakinra
Medical subject headings
Cerebral Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AnakinraDrug

    Also called Kineret

    Anakinra treatment is started within 8 hours of symptom onset

Study groups in NCT04834388
Study groupRoleWhat they receive
Anakinra High doseExperimental500mg i.v. loading dose, followed by continuous iv infusion with 2mg/kg/h over 3 days
Receives: Drug: Anakinra
Anakinra Low doseExperimental100mg s.c. loading dose, followed by subcutaneous administration of 100mg twice daily for 3 days.
Receives: Drug: Anakinra
Standard careNo interventionStandard care group

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Perihematomal oedema

    Measured as Oedema Extension Distance (OED/EED)

    Measured: 7 days after ICH onset

Secondary outcomes (4)

  1. Adverse events of special interest (AESI) and serious adverse events (SAE)

    Number of events in the control group versus the treatment groups

    Measured: 90 days

  2. Blood brain barriere leakage

    Measured as Ktrans on DCE-MRI

    Measured: 7 days

  3. Levels of serum inflammatory markers (IL-1β, IL-6, hsCRP)

    IL-1β, IL-6, hsCRP

    Measured: 7 days

  4. Functional outcome

    Ordinal shift in functional outcome on the modified rankin scale (mRS) (comparing the intervention group to the controls), assessed with the modified Rankin Scale (mRS) at 3 months. This is a six point scale in which a score of 0 means no symptoms at all, a higher score means more impairment, and a score of 6 means the participant is dead.

    Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2021
  2. Study start10 Aug 2022
  3. Primary completionSep 2025 (estimated)
  4. Study completionDec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
PROBE design
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
75 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04834388
Sponsor's protocol ID
NL76607.091.21
Acronym
ACTION
Status last verified
Nov 2023
First submitted
29 Mar 2021
Last updated
18 Nov 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cliteur MP, van der Kolk AG, Hannink G, Hofmeijer J, Jolink W, Klijn C, Schreuder F. Anakinra in cerebral haemorrhage to target secondary injury resulting from neuroinflammation (ACTION): Study protocol of a phase II randomised clinical trial. Eur Stroke J. 2024 Mar;9(1):265-273. doi: 10.1177/23969873231200686. Epub 2023 Sep 15.

    PubMed 37713268

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anakinra in people with Intracerebral Hemorrhage, run by Radboud University Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Floris H.B.M Schreuder, MD PhD (+31650155755, floris.schreuder@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Perihematomal oedema (time frame: 7 days after ICH onset). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04834388, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2024.

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