Condition category
Nervous System Diseases
Date applied
24/06/2015
Date assigned
24/06/2015
Last edited
24/06/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Encephalitis is a rare, serious condition that causes inflammation of the brain. In this study, we would like to find out whether early treatment with intravenous immunoglobulin (IVIG) benefits children with encephalitis. We will be comparing the children who are treated with IVIG to those who are not.

Who can participate?
Children aged from 6 weeks to 16 years and diagnosed with encephalitis, admitted to NHS hospitals in the United Kingdom.

What does the study involve?
Participants are randomly allocated to two groups to receive either IVIG or placebo (a ‘treatment’ that looks like IVIG but has no medical effect in encephalitis) in addition to standard treatment. All children are followed up for 12 months after treatment and we are collecting information on their health and wellbeing through the use of questionnaires, brain scan and neuropsychologist (an expert who studies how the brain works) assessment.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
University of Oxford, Department of Paediatrics (UK)

When is the study starting and how long is it expected to run for?
August 2015 to July 2020

Who is funding the study?
The CSL Behring Foundation and National Institute for Health Research

Who is the main contact?
Dr Mildred Iro

Trial website

Contact information

Type

Scientific

Primary contact

Dr Mildred Iro

ORCID ID

Contact details

University of Oxford
Department of Paediatrics
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Additional identifiers

EudraCT number

2014-002997-35

ClinicalTrials.gov number

NCT02308982

Protocol/serial number

18993

Study information

Scientific title

A phase III multicentre randomised, double blind, placebo controlled trial to assess the role of intravenous immunoglobulin in the management of children with encephalitis (The IgNiTE study)

Acronym

IgNiTE

Study hypothesis

The aim of this study is to determine whether early treatment with intravenous immunoglobulin (IVIG) benefits children with encephalitis.

Ethics approval

14/SC/1416; First MREC approval date 29/12/2014

Study design

Randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Topic: Children, Infectious diseases and microbiology, Neurological disorders; Subtopic: All Diagnoses, Infection (all Subtopics), Neurological (all Subtopics); Disease: Infectious diseases and microbiology , All Diseases, Neuro-muscular and Encephalitis

Intervention

1. Intravenous immunoglobulin, Treatment group: 2 doses (1g/kg per dose) of intravenous immunoglobulin administered 24 hours apart, in addition to standard treatment
2. Matching placebo, Control group: 2 doses of placebo administered 24 hours apart, in addition to standard treatment. Volume equivalent to 1g/kg/dose of intravenous immunoglobulin

Intervention type

Other

Phase

Phase III

Drug names

Primary outcome measures

Proportion of participants in both study groups making good recovery (GOSE-Peds score of 2 or lower); Timepoint(s): 12 months post randomisation

Secondary outcome measures

1. Comparison of duration of invasive ventilation (if ventilated) between both study groups; Timepoint(s): During the acute admission period
2. Comparison of anti-epileptic treatment use in participants in both study groups; Timepoint(s): Up to 12 months post randomisation
3. Comparison of auto-antibody levels in blood and/or CSF in both study groups; Timepoint(s): Before receipt of study treatment and up to 6 months after treatment
4. Comparison of brain imaging findings of participants in both study groups; Timepoint(s): 6 months post randomisation
5. Comparison of cognitive function between participants in both study groups; Timepoint(s): At 12 months post randomisation
6. Comparison of duration of hospitalisation between both study groups; Timepoint(s): During acute admission
7. Comparison of length of stay on the intensive care unit between both study groups; Timepoint(s): During acute admission
8. Comparison of neurological outcomes using age appropriate questionnaires (e.g SDQ, ABAS-II, GMFCS); Timepoint(s): Up to 12 months post randomisation
9. Number of deaths in children enrolled to the study and comparison between both study groups; Timepoint(s): 12 months post randomisation
10. Occurence of adverse events of special interest in both study groups; Timepoint(s): Within 5 days of study treatment
11. Occurrence of serious adverse events in study participants; Timepoint(s): 6 months post randomisation; Presence and levels of specific autoantibodies in blood and/or CSF; Timepoint(s): Before receipt of study treatment
12. Proportion of participants in both study groups diagnosed subsequently with epilepsy; Timepoint(s): Up to 12 months post randomisation
13. Proportion of participants in both study groups with GOSE-Peds score of 2 or lower; Timepoint(s): 6 months post randomisation

Overall trial start date

03/08/2015

Overall trial end date

31/07/2020

Reason abandoned

Eligibility

Participant inclusion criteria

1. 6 weeks to 16 years of age (day before 17th birthday)
AND
2. Acute (within 24 hours) or subacute (between 24 hours and 4 weeks) onset of altered mental state (reduced or altered conscious level, irritability, altered personality or behaviour, lethargy) not attributable to a metabolic cause
AND
3. At least two of:
3.1. Fever >38oC within 72 hours before or after presentation to hospital
3.2. Brain imaging evidence consistent with encephalitis or immunemediated encephalopathy that is either new from prior studies or appears acute in onset
3.3. CSF pleocytosis >4 white blood cells (WBCs)/microlitre
3.4. Generalised or partial seizures not fully attributable to a preexisting seizure disorder
3.5. New onset focal neurological signs (including movement disorders) for >6 hours
3.6. Abnormality on EEG that is consistent with encephalitis and not clearly attributable to another cause.
AND
4. Parent/guardian/ legal representative/child (if 16 years at the time of enrolment and has capacity to give consent) able to give informed consent and assent (if <16 years and has capacity)
Target Gender: Male & Female; Upper Age Limit 16 years ; Lower Age Limit 6 weeks

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 308; UK Sample Size: 308

Participant exclusion criteria

1. High clinical suspicion of bacterial meningitis or TB meningitis (for example: presence of frankly purulent CSF; CSF WBCs >1000/microlitre; bacteria on Gram stain and/or culture)
2. Receipt of any IVIg product during the index admission where this was administered prior to obtaining written informed consent for the IgNiTE study
3. Traumatic brain injury
4. Known metabolic encephalopathy
5. Toxic encephalopathy (i.e. encephalopathy secondary to exposure to intoxicants, including alcohol, prescription or recreational drugs)
6. Hypertensive encephalopathy/posterior reversible encephalopathy syndrome
7. Preexisting demyelinating disorder; preexisting antibody mediated CNS disorder; preexisting CSF diversion
8. Ischaemic or haemorrhagic stroke
9. Children with a contraindication to IVIG or albumin (i.e. history of anaphylactic reaction to IVIG or albumin, known IgA deficiency and history of hypersensitisation)
10. Known hypercoagulable state
11. Significant renal impairment defined as GFR of 29mls/min/1.73m2 and below (Chronic Kidney Disease Stage 4)
12. Known hyperprolinaemia
13. Known to be pregnant
14. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial
15. Participants who are being actively followed up in another research trial involving an investigational medicinal product
16. Administration of study drug not feasible within 120 hours from hospital presentation for the index admission for new patients admitted to a study hospital OR 72 hours from admission to the study hospital for patients transferred from other hospitals, as determined by the study team
17. Any other condition which, in the opinion of the investigator, may interfere with the ability to fulfil study requirements, especially relating to the primary objective of the study (this includes plans to be outside the UK for more than 12 months after enrolment)

Recruitment start date

03/08/2015

Recruitment end date

31/07/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Oxford
Department of Paediatrics Headley Way Headington
Oxford
OX3 9DU
United Kingdom

Sponsor information

Organisation

University of Oxford

Sponsor details

Old Road
Headington
Oxford
OX3 7LF
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

CSL Behring Foundation for Research and Advancement of Patient Health

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United States of America

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

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 provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes