IgNiTE: Immunoglobulin in the treatment of encephalitis
| ISRCTN | ISRCTN15791925 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15791925 |
| EudraCT/CTIS number | 2014-002997-35 |
| ClinicalTrials.gov number | NCT02308982 |
| Secondary identifying numbers | 18993 |
- Submission date
- 24/06/2015
- Registration date
- 24/06/2015
- Last edited
- 13/11/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims
Encephalitis is a rare, serious condition that causes inflammation of the brain. The aim of this study is to find out whether early treatment with intravenous immunoglobulin (IVIG) benefits children with encephalitis. The children who are treated with IVIG will be compared 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 (UK)
Who is the main contact?
Dr Mildred Iro
Contact information
Scientific
University of Oxford
Department of Paediatrics
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
| Mildred.iro@paediatrics.ox.ac.uk |
Study information
| Study design | Randomized; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| 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) |
| 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(s) | 14/SC/1416; First MREC approval date 29/12/2014 |
| Condition | 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 | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | IVIG |
| Primary outcome measure | 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 study start date | 03/08/2015 |
| Overall study end date | 31/07/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 6 Weeks |
| Upper age limit | 16 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 308; UK Sample Size: 308 |
| Total final enrolment | 18 |
| 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 immune-mediated 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) |
| 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
- England
- United Kingdom
Study participating centre
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Sponsor information
Hospital/treatment centre
Old Road
Headington
Oxford
OX3 7LF
England
United Kingdom
| no@email.provided | |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Government
Private sector organisation / Trusts, charities, foundations (both public and private)
- Location
- United States of America
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/01/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal around one year after the trial ends |
| IPD sharing plan | All data requests should be submitted to the primary contact Prof. Andrew J Pollard (andrew.pollard@paediatrics.ox.ac.uk) for consideration. A fully anonymised dataset will be shared upon reasonable request. The anonymisation will take into account the small sample size to ensure that no individual participant could be identified from any of the data shared. Dates of availability: 2024. Consent was required from all participants, all consent for data was obtained. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 03/11/2016 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 09/11/2023 | 13/11/2023 | Yes | No |
Editorial Notes
13/11/2023: Publication reference added.
21/09/2023: IPD sharing plan, intention to publish date and total final enrolment added.
09/07/2020: The trial contact details have been made publicly visible.
03/04/2019: The condition has been changed from "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" to "Encephalitis" following a request from the NIHR.
01/03/2019: Internal review.
23/10/2017: Publication reference added.
19/10/2017: Recruitment on hold pending funding review, follow up ongoing.
