NCT04834388

Brief 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.

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
75

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Aug 2022

Typical duration for phase_2

Geographic Reach
1 country

1 active site

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

March 29, 2021

Completed
10 days until next milestone

First Posted

Study publicly available on registry

April 8, 2021

Completed
1.3 years until next milestone

Study Start

First participant enrolled

August 10, 2022

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2025

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2025

Completed
Last Updated

November 18, 2024

Status Verified

November 1, 2023

Enrollment Period

3.1 years

First QC Date

March 29, 2021

Last Update Submit

November 14, 2024

Conditions

Outcome Measures

Primary Outcomes (1)

  • Perihematomal oedema

    Measured as Oedema Extension Distance (OED/EED)

    7 days after ICH onset

Secondary Outcomes (4)

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

    90 days

  • Blood brain barriere leakage

    7 days

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

    7 days

  • Functional outcome

    90 days

Study Arms (3)

Anakinra High dose

EXPERIMENTAL

500mg i.v. loading dose, followed by continuous iv infusion with 2mg/kg/h over 3 days

Drug: Anakinra

Anakinra Low dose

EXPERIMENTAL

100mg s.c. loading dose, followed by subcutaneous administration of 100mg twice daily for 3 days.

Drug: Anakinra

Standard care

NO INTERVENTION

Standard care group

Interventions

Anakinra treatment is started within 8 hours of symptom onset

Also known as: Kineret
Anakinra High doseAnakinra Low dose

Eligibility Criteria

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

You may qualify if:

  • 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.

You may not qualify if:

  • 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);
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Radboudumc

Nijmegen, Netherlands

RECRUITING

Related Publications (1)

  • 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.

    PMID: 37713268BACKGROUND

Related Links

MeSH Terms

Conditions

Cerebral 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

  • F.H.B.M. Schreuder, MD PhD

    Radboud University Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Floris H.B.M Schreuder, MD PhD

CONTACT

Maaike P. Cliteur, MD

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: PROBE design
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 29, 2021

First Posted

April 8, 2021

Study Start

August 10, 2022

Primary Completion

September 1, 2025

Study Completion

December 1, 2025

Last Updated

November 18, 2024

Record last verified: 2023-11

Data Sharing

IPD Sharing
Will not share

Locations