Clinical Trial: Investigating the Role of Early Intravenous Immunoglobulin Treatment for Children With Encephalitis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase III Multi-centre Randomised, Double Blind, Placebo Controlled Trial to Assess the Role of Intravenous Immunoglobulin in the Management of Children With Encephalitis

Brief Summary:

This is a phase III multi-centre randomised, double blind, placebo controlled trial to assess the role of intravenous immunoglobulin in the treatment of children with encephalitis. The primary objective is to find out whether early use of IVIG treatment improves neurological outcomes of children with encephalitis.

308 children with encephalitis, aged 6 weeks to 16 years will be recruited in 30 hospitals in the United Kingdom. Participants will be randomised to receive two doses of IVIG or matching placebo in addition to other standard treatments, within the first five days of hospital admission.

Each participant will be followed up for 12 months. During this period, information on clinical, radiological and laboratory investigations will be collected. Neurological outcomes will be assessed by the use of questionnaires at 6 and 12 months, and a neuropsychological assessment at 12 months.


Detailed Summary:

Encephalitis is a syndrome of neurological dysfunction caused by inflammation of the brain parenchyma, resulting in altered mental status, seizures, and/or focal neurologic deficits, usually accompanied by laboratory and radiological evidence of brain inflammation. The worldwide annual incidence of encephalitis ranges from 3.5 to 7.4 per 100,000, rising to 16 per 100,000 in children. In the United Kingdom, Public Health England (formerly the Health Protection Agency) reports an annual rate of 1.5 cases per 100,000 in the general population and 2.8 per 100,000 in children, with the highest incidence in infants under 1 year of age of 8.7 per 100,000.

Despite the use of current standard treatments, mortality of 7-10% and morbidity of up to 50% are still being reported. Encephalitis also imposes a substantial economic and resource burden on healthcare services. Strategies to reduce the disability in patients with encephalitis are therefore required.

There is increasing evidence from case reports of a beneficial role of IVIG treatment in encephalitis. However, in clinical practice, the use of IVIG in encephalitis varies. The variation in practice is in most part due to a lack of class 1 evidence to support the use of IVIG in encephalitis. For the immune mediated forms of encephalitis, IVIG is typically used after inevitable delay (by weeks in some cases) while alternative diagnoses are being excluded, or a definitive diagnosis is obtained. In other cases, IVIG is used usually as a last treatment option where clinical improvement is slow. Again, this is usually after several days from hospital admission. Delays in the institution of appropriate treatment in encephalitis may contribute to the high rate of morbidity and mortality, prolonged hospitalisation and associated costs from encephalitis. In particular, it is currently unkn
Sponsor: University of Oxford

Current Primary Outcome: 'Good recovery' defined by a score of 2 or lower, assessed using the Pediatric version of the Glasgow Outcome Scale Extended. [ Time Frame: 12 months (+/- 4 weeks) post randomisation ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Neurological outcomes using age appropriate questionnaires and neuropsychology assessment [ Time Frame: Up to 12 months post randomisation ]
  • Brain MRI scan changes [ Time Frame: Up to 6 months post randomisation ]
  • Local and systemic adverse events of interest and serious adverse events [ Time Frame: Up to 6 months post randomisation ]
  • Presence of auto-antibodies in blood and/or cerebrospinal fluid (CSF) [ Time Frame: Before and after study treatment ]
  • Clinical outcomes such as length of hospitalisation, need for intensive care admission, duration of invasive ventilation, frequency of seizures and need for anti-epileptic treatment [ Time Frame: Up to 12 months post randomisation ]


Original Secondary Outcome: Same as current

Information By: University of Oxford

Dates:
Date Received: December 1, 2014
Date Started: January 2016
Date Completion: February 2020
Last Updated: November 29, 2016
Last Verified: October 2016