Plain English Summary
Background and study aims
A spontaneous subarachnoid haemorrhage (SAH) is a serious medical condition caused by sudden bleeding over the surface of the brain. It is most often caused when a bulge in a blood vessel wall (brain aneurysm) bursts (ruptures) because the vessel wall has become weakened over time. Following rupture blood pools inside the skull (which cannot expand due to its rigid structure) leading to pressure on the brain and starving it of oxygen (cerebral ischaemia) causing further brain damage. To treat this, a hole is usually drilled into the skull and a tube (external ventricular drain) is placed inside so that the collected blood can escape, lowering pressure on the brain. When a person sustains a severe injury chemicals are released in the body to help start the healing process, such as the protein Interleukin−1 (IL−1) which triggers inflammation (swelling). Studies have shown that IL-1 actually contributes to the damage caused cerebral ischaemia. Kineret® is a drug which acts by blocking the action of IL-1. The aim of this study is to find out whether Kineret® can change the concentration of the inflammatory biomarkers (natural chemical indictors of inflammation) in the blood and cerebral spinal fluid (fluid that cushions the brain).
Who can participate?
Patients aged 16 years or over who have had a spontaneous subarachnoid haemorrhage (SAH) and have had an external ventricular drain (EVD) fitted.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group are a bolus (one-off large dose) injection of 500mg Kineret® into a vein (IV) over 1 minute. Immediately afterwards, the participants are started on a drip (infusion) of Kineret® which is given slowly, over 24 hours. Those in the second group are given a blous injection of a placebo (dummy) over one minute, followed by an infusion of saline (salt water) and placebo (dummy) over 24 hours. Participants in both groups have samples of blood and cerebral spinal fluid (CFS) taken at the start of the study and then after 6, 12, 24, 36, 48 and 72 hours in order to measure the concentration of the chemical indicators of inflammation (inflammatory biomarkers).
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
Brain Injury Research Group, Salford Royal NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
June 2009 to April 2010
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Dr Pippa Tyrell
pippa.tyrrell@manchester.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Pippa Tyrrell
ORCID ID
http://orcid.org/0000-0001-9609-1231
Contact details
Brain Injury Research Group
Clinical Sciences Building
Salford Royal Foundation Trust
Stott Lane
Salford
M6 8HD
United Kingdom
+44 (0)161 206 2018
pippa.tyrrell@manchester.ac.uk
Additional identifiers
EudraCT number
2007-005836-98
ClinicalTrials.gov number
Protocol/serial number
MRC ref: G0502030; Protocol version 2 16-07-2008
Study information
Scientific title
The effect of Kineret® on brain biomarkers in patients with subarachnoid haemorrhage: Double-blind randomised placebo-controlled trial
Acronym
Study hypothesis
The presence of Kineret® in the cerebrospinal fluid (CSF) at concentrations that have been shown to be experimentally therapeutic decrease concentrations of inflammatory biomarkers in the CNS.
Ethics approval
Added 05/06/2009: Wales REC approved on the 29th January 2009 (ref: 09/MRE09/1)
Study design
Single-centre double-blind randomised placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Subarachnoid haemorrhage
Intervention
The study is a double-blind randomised controlled trial of Kineret® with participants with an external ventricular drain (EVD) inserted as part of their clinical care. Participants will be randomised to receive a regime of 500 mg bolus dose plus a 10 mg/kg/h intravenous infusion for 24 hours of Kineret® or placebo, which has been identified from a previous pharmacokinetic dose-finding study. Blood and CSF will be taken immediately prior to bolus dose of IMP/placebo (baseline); and at 6, 12 and 24 hours (during period of infusion) and then at 36, 48 and 72 hours (from time of bolus injection). A final sample will be obtained at Day 7 (study end) if the participant still has an EVD in-situ. Analysis of these samples will show the effect of Kineret® on inflammatory markers and allow the concentration of the markers to be measured.
Intervention type
Drug
Phase
Phase IV
Drug names
Interleukin-1 (IL-1), (Kineret®)
Primary outcome measure
To determine whether intravenously administered Kineret® causes a decrease in the concentration of central inflammatory biomarkers in the blood and CSF samples following SAH compared to placebo. The following markers will be assessed: C-reactive protein (CRP), IL-1RA, IL-1a, IL-1ß, IL-6, IL-8, IL-10
Blood and CSF samples will be taken immediately prior to bolus dose of IMP/placebo (baseline); and at 6, 12 and 24 hours (during period of infusion) and then at 36, 48 and 72 hours (from time of bolus injection). A final sample will be obtained at Day 7 (study end) if the participant still has an EVD in-situ.
Secondary outcome measures
No secondary outcome measures
Overall trial start date
01/06/2009
Overall trial end date
30/04/2010
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Both males and females, aged 16 years or above
2. Patients with confirmed spontaneous subarachnoid haemorrhage (SAH) who have had an external ventricular drain (EVD) inserted as part of their clinical care
3. No concomitant health problems that, in the opinion of the Principal Investigator or Chief Investigator or designee, would interfere with participation, administration of study treatment or assessment of outcomes including safety, for example, pre-existing malignancy
4. No confirmed or suspected serious infection at the time of study entry
5. Renal function within normal limits (serum creatinine <177 µmol/l)
6. Willing and able to give informed consent or consent available from a patient representative (personal, usually the next of kin) for study inclusion including agreement in principle to receive study intervention and undergo all study assessments
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
32
Participant exclusion criteria
1. Known or suspected infection at the time of consideration for the study
2. Known allergy to E. coli or any of the constituents of the study medication as established from the patient themselves, reliable representative and clinical records
3. Previous or concurrent treatment with anakinra or Kineret®; known at the time of study entry
4. Previous or current treatment with medication suspected of interacting with Kineret®, such as TNF-á inhibitors
5. Evidence of serious infection
6. Known to have participated in a clinical trial of an investigational agent or device in the previous 30 days or for the period determined by the protocol of the study the patient has taken part in
7. Known pregnancy or breast-feeding
8. Clinically significant concurrent medical condition, which in the Chief Investigator's (or designee's) discretion, could affect the safety, tolerability, or efficacy in this study
9. Previous inclusion in current study (known prior to inclusion)
10. Inability or unwillingness of patient or patient's personal representative to give written informed consent
Recruitment start date
01/06/2009
Recruitment end date
30/04/2010
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Brain Injury Research Group
Salford Royal NHS Foundation Trust
Salford
M6 8HD
United Kingdom
Sponsor information
Organisation
Salford Royal Hospitals NHS Trust (UK)
Sponsor details
Research and Development Directorate
Clinical Sciences Building
Stott Lane
Salford
M6 8HD
United Kingdom
+44 (0)161 206 7373/5755
lloyd.gregory@manchester.ac.uk
Sponsor type
Government
Website
http://www.hope-academic.org.uk/Academic/researchdevelopment/
Funders
Funder type
Government
Funder name
Medical Research Council (UK) (Grant ref: G0502030)
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration.
Intention to publish date
Participant level data
Not expected to be available
Basic results (scientific)
Publication list