Clinical Trial Results:
Does subcutaneous interleukin-1 receptor antagonist reduce inflammation following subarachnoid haemorrhage?
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Summary
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EudraCT number |
2011-001855-35 |
Trial protocol |
GB |
Global end of trial date |
13 Oct 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Nov 2019
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First version publication date |
29 Nov 2019
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Other versions |
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Summary report(s) |
publication SCIL-SAH JNS |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
2011.087neuro
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Additional study identifiers
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ISRCTN number |
ISRCTN25048895 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
SALFORD ROYAL NHS FOUNDATION TRUST
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Sponsor organisation address |
ECCLES NEW ROAD, SALFORD, United Kingdom, M5 5AP
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Public contact |
Prof Andrew King (Pippa Tyrrell, original CI has retired), Salford Royal NHS Foundation Trust, 44 1612064265, andrew.king@manchester.ac.uk
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Scientific contact |
Prof Andrew King (Pippa Tyrrell, original CI has retired), Salford Royal NHS Foundation Trust, 44 1612064265, andrew.king@manchester.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Oct 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 Oct 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Oct 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
What effect does the specific anti-inflammatory drug (IL-1Ra) have on the levels of a specific inflammatory protein (IL-6) in blood between 3-8 days after a brain haemorrhage?
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Protection of trial subjects |
The known risks associated with sampling of blood and from administering the investigational medicinal product via subcutaneous route were managed by the research team. Blood samples were collected from existing venous/arterial lines whenever possible and research blood sampling was collected at the same time as clinical blood samples to minimise the risk of pain/discomfort for participants.
Administration of IMP in the treatment group was subcutaneous and site of administration was varied for each injection to avoid risk of injection site reaction and bruising. IMP was administered slowly and warmed to room temperature prior to administration in line with SPC, to minimise discomfort.
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Background therapy |
Open-label, randomised trial of interleukin-1 receptor antagonist (IL-1Ra). No placebo | ||
Evidence for comparator |
No comparator | ||
Actual start date of recruitment |
17 Oct 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 136
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Worldwide total number of subjects |
136
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EEA total number of subjects |
136
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
114
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From 65 to 84 years |
22
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants meeting eligibility were recruited from three NHS hospital sites in England between 17/10/2011 and 07/11/2014. Participants were followed up at 6 months post subarachnoid haemorrhage by telephone and outcome assessed using Glasgow Outcome score (secondary outcome). Final telephone outcome assessment performed May, 2015 | |||||||||||||||
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Pre-assignment
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Screening details |
Patients presenting to neurosurgical centres within 72h of onset of spontaneous subarachnoid haemorrhage (SAH) were screened for eligibility to participate (473). In addition to exclusion criteria reasons for not recruitment were late presentation to site, unable to confirm aneurysm within timeframe, no consent available | |||||||||||||||
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Period 1
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Period 1 title |
Baseline period (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Blinding implementation details |
laboratory staff were blinded to treatment arm
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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treatment arm | |||||||||||||||
Arm description |
Participant randomised to receive twice daily subcutaneous injections of investigational drug (interleukin-1 receptor antagonist; IL-1Ra/anakinra) | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
interleukin-1 receptor antagonist; IL-1Ra/anakinra
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Investigational medicinal product code |
L04AA14
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Other name |
Kineret, L04AC03
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Pharmaceutical forms |
Solution for solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
100mg in 0.6ml pre-filled syringe administered twice daily (12hourly intervals) for maximum of 21 days from symptom-onset (ictus)
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Arm title
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control arm | |||||||||||||||
Arm description |
Participants randomised to standard care without addition of IMP. Participants completed all other protocol/assessment | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
treatment arm
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Reporting group description |
Participant randomised to receive twice daily subcutaneous injections of investigational drug (interleukin-1 receptor antagonist; IL-1Ra/anakinra) | ||||||||||||||||||||||||||||||||||||||||
Reporting group title |
control arm
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Reporting group description |
Participants randomised to standard care without addition of IMP. Participants completed all other protocol/assessment | ||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
treatment arm
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Reporting group description |
Participant randomised to receive twice daily subcutaneous injections of investigational drug (interleukin-1 receptor antagonist; IL-1Ra/anakinra) | ||
Reporting group title |
control arm
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Reporting group description |
Participants randomised to standard care without addition of IMP. Participants completed all other protocol/assessment | ||
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End point title |
Change in levels of IL-6 between treated and untreated groups | ||||||||||||
End point description |
Linear measurement of plasma IL-6 collected daily from baseline (within 72 hours of onset of subarachnoid haemorrhage) to day 8 post symptom onset between treated and untreated groups
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End point type |
Primary
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End point timeframe |
Plasma IL-6 concentrations daily from baseline (pre-randomisation) to day 8 post ictus
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Statistical analysis title |
statistical analysis | ||||||||||||
Statistical analysis description |
The primary outcome measure was the area under the curve (AUC) for natural log (ln) (IL-6) from Days 3 to 8. Patients were included in the analysis if they provided ≥ 4 blood samples from a possible total of 6. Secondary outcomes were corresponding AUCs for other biomarkers, all biomarkers up to Day 21, and Glasgow Outcome Scale–extended (GOS-E) score at 6 months. Sample size calculation was based on effects observed for ln(IL-6) and ln(CRP) after 72 hours of IV infusion in patients wit
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Comparison groups |
treatment arm v control arm
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Number of subjects included in analysis |
125
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||
P-value |
= 0.005 | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Confidence interval |
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| Notes [1] - Area under curve |
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Adverse events information
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Timeframe for reporting adverse events |
Treated group
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Adverse event reporting additional description |
Adverse events for participants who received at least one dose of IMP within 72h of SAH to day 21 post SAH
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
treatment arm
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Reporting group description |
Participant randomised to receive twice daily subcutaneous injections of investigational drug (interleukin-1 receptor antagonist; IL-1Ra/anakinra) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
control arm
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Reporting group description |
Participants randomised to standard care without addition of IMP. Participants completed all other protocol/assessment | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Date |
Amendment |
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30 Apr 2012 |
A. To undertake extra analysis on blood collected from trial participants;
B. To invite trial participants to participate in a sub-study if they have an external ventricular drain (EVD) inserted as part of their clinical care;
C. To recruit a number of healthy volunteers to act as controls to the participants in the main trial.
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01 Apr 2013 |
Addition of two new research sites
Amendment to protocol on conduct of the study at the new sites
Amendment to documents in initial application i.e. additional patient information/consent for new study sites,
Amendment to protocol regarding extension of timeframe for 6 month outcome assessment
Amendment to protocol regarding submission of adverse event reports to study Sponsor
Extension to study period of 12 months |
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12 Dec 2013 |
outlining the temporary arrangements to cover absence of the Chief Investigator |
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24 Mar 2014 |
reinstatement of Prof Pippa Tyrrell as Chief Investigator |
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27 Apr 2015 |
Permission to collect additional outcome information on participants recruited to the trial at Salford Royal NHS Foundation Trust |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/28298024 |
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