Trial record 17 of 161 for:    Encephalitis

Safety and Efficacy Study of Intravenous Immunoglobulin to Treat Japanese Encephalitis

This study has been completed.
Sponsor:
Collaborators:
Kanti Children's Hospital
B.P. Koirala Institute of Health Sciences
Information provided by (Responsible Party):
Ajit Rayamajhi, University of Liverpool
ClinicalTrials.gov Identifier:
NCT01856205
First received: May 5, 2013
Last updated: May 18, 2013
Last verified: May 2013
  Purpose

Japanese encephalitis is caused by a viral infection of the brain transmitted by the bite of an infected mosquito. Patients with Japanese encephalitis can rapidly develop worsening conscious level and seizures. Around a third will die from the infection and half of survivors have serious long-term neurological disability. The majority of those affected are children. There are many causes of viral encephalitis, however Japanese encephalitis virus is the most common cause worldwide with over 60,000 cases annually. It occurs over much of Asia and the geographical range is expanding. There is no specific treatment for Japanese encephalitis virus, although several have been trialed. In this study we examined the effect of a new treatment, called intravenous immunoglobulin, on children with Japanese encephalitis in Nepal. Prior studies have suggested intravenous immunoglobulin may neutralize Japanese encephalitis virus and suppress damaging inflammation in the brain. It has previously been used in individual cases but never examined in a randomized trial. There was recently a trial of IVIG in West Nile encephalitis in the United States, in which Professor Solomon was on the Scientific Advisory Committee. In this study we will look if intravenous immunoglobulin is safe in this context, and that this treatment may alter the way the immune system manages the infection. Therefore, in this pilot study we will test the hypothesis that IVIG can be safely given to children with suspected JE, with no increased risk of serious adverse events compared with placebo. The aim of this proposal is to conduct a pilot safety and tolerability randomized placebo controlled trial of intravenous immunoglobulin (IVIG) in patients with Japanese encephalitis, to explore the relationship between JEV viral load, pro-inflammatory markers called cytokines and blood brain barrier markers, and the effect of IVIG on these relationships.


Condition Intervention Phase
Japanese Encephalitis
Drug: Intravenous immunoglobulin [ImmunoRel™ (batch 20081217)]
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double Blind Placebo Controlled Trial to Assess the Safety and Efficacy of Intravenous Immunoglobulin (IVIG) in Children With Japanese Encephalitis in Nepal

Resource links provided by NLM:


Further study details as provided by University of Liverpool:

Primary Outcome Measures:
  • Evidence of side effects of study drug such as infusion site reaction, diarrhea, rise in blood pressure and change in urinary output [ Time Frame: Every 12 hours after administration of study drug upto discharge, which is on average eigth day (192 hours) of hospital admission ] [ Designated as safety issue: Yes ]
    Patients will be monitored for side effects such as infusion site reaction, diarrhea, rise in blood pressure (in mm Hg) and change in urinary output (in ml/Kg/hour) every 12 hours from first day of commencing treatment until until death or discharge. Patient on average are administered the study drug on the first day of admission. The study drug is administered daily for 5 days. Patients are discharged on an average on eighth day (192 hours) of hospital admission.


Secondary Outcome Measures:
  • Death or neurological sequelae [ Time Frame: At the time of discharge, an expected average of eighth day of admission and again at 6 months after discharge ] [ Designated as safety issue: No ]

    At the time of discharge(expected average of eighth day of admission) or death: Time to death, to recover from coma, to sit independently, to stand independently, to walk at least 5m independently, and to leave hospital.

    At 6 months after discharge: history of further seizures, behavioral changes, evidence of recovery of neurological sequelae such as assessment of ability to sit independently, to stand independently, to walk at least 5 meters independently.



Other Outcome Measures:
  • Serum JEV PRNT50 level (immunological marker) [ Time Frame: Measured at 3 time points: pre-treatment (just before first dose of study drug on first day), mid-treatment (just prior to fourth dose on fourth day) and post-treatment (one hour after fifth dose on fifth day). ] [ Designated as safety issue: No ]
    Pre-treatment was immediately prior to the first dose of study drug on the first day, mid-treatment was immediately prior to the 4th dose and post-treatment was 1hour after administering the fifth dose of the study drug.


Enrollment: 22
Study Start Date: May 2009
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: IVIG in JE (JE-positive)
We randomly allocated patients to treatment with IVIG or placebo. Children received either saline or intravenous immunoglobulin (IVIG) [ImmunoRel™ (batch 20081217)] at a dose of 400mg/kg/day for 5 days or an equivalent volume of 0.9% normal saline given intravenous at the rate of 0.01 to 0.02 ml/kg body weight/minute. All investigators, care providers and participants were blinded of the study drug. A second sealed envelope was kept with the patient's notes in case a physician urgently needed to know which drug a patient had received.
Drug: Intravenous immunoglobulin [ImmunoRel™ (batch 20081217)]

IVIG group received 400mg/kg/day intravenous at the rate of 0.01 to 0.02 ml/kg body weight/minute for 5 days or appearance of side effect or adverse events.

Placebo group received 0.9% saline intravenous at similar rate.

Placebo Comparator: IVIG in Non-JE(JE-negative)
We randomly allocated patients to treatment with IVIG or placebo. Children received either saline or intravenous immunoglobulin (IVIG) [ImmunoRel™ (batch 20081217)] at a dose of 400mg/kg/day for 5 days or an equivalent volume of 0.9% normal saline given intravenous at the rate of 0.01 to 0.02 ml/kg body weight/minute. All investigators, care providers and participants were blinded of the study drug. A second sealed envelope was kept with the patient's notes in case a physician urgently needed to know which drug a patient had received.
Drug: Intravenous immunoglobulin [ImmunoRel™ (batch 20081217)]

IVIG group received 400mg/kg/day intravenous at the rate of 0.01 to 0.02 ml/kg body weight/minute for 5 days or appearance of side effect or adverse events.

Placebo group received 0.9% saline intravenous at similar rate.


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 14 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children aged between 1 and 14 years who had clinically diagnosed encephalitis on the basis of history of fever that lasted less than 14 days, altered consciousness with or without a history of new onset seizures with CSF finding of white cell count less than 1000 cells/mm3 with no organisms on Gram stain and a CSF: plasma glucose ratio > 40% admitted in Kanti Children's Hospital and BP Koirala Institute of Health Sciences, Nepal.

Exclusion Criteria:

  • Asexual Plasmodium falciparum parasites in blood

    • Coma appears secondary to other systemic condition, eg hepatic failure, cardiac failure, toxins.
    • Patients who have documented antibiotic treatment before admission and in whom partially treated bacterial meningitis appears more likely than encephalitis
    • Children with simple febrile convulsions, defined as a single seizure lasting less than 15 minutes followed by full recovery of consciousness within 60 minutes.
    • Pregnant or breastfeeding females
    • Children with a GCS of 3/15, who were receiving artificial ventilation without signs of spontaneous respiration, and with absent oculocephalic reflex.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01856205

Locations
Nepal
Kanti Children's Hospital
Kathmandu, Bagmati, Nepal, 44616
BP Koirala Institute of Health Sciences
Dharan, Koshi, Nepal
Sponsors and Collaborators
University of Liverpool
Kanti Children's Hospital
B.P. Koirala Institute of Health Sciences
Investigators
Study Chair: Tom Solomon, MRCP, PhD Director,Institute of Infection and Global Health, University of Liverpool, Apex Building, 8 West Derby Street, Liverpool, L69 7BE, UK , Head- Liverpool Brain Infection Group
Principal Investigator: Ajit Rayamajhi, MBBS, MD Institute of Infection and Global Health, University of Liverpool, Liverpool, UK & Kanti Children's Hospital, Maharajgunj, Kathmandu, Nepal
Study Director: Sam Nightingale, MRCP Institute of Infection and Global Health, University of Liverpool, Apex Building, 8 West Derby Street, Liverpool, L69 7BE, UK
  More Information

Publications:

Responsible Party: Ajit Rayamajhi, Clinical Research Fellow (PhD Student), University of Liverpool
ClinicalTrials.gov Identifier: NCT01856205     History of Changes
Other Study ID Numbers: IVIG607
Study First Received: May 5, 2013
Last Updated: May 18, 2013
Health Authority: Nepal: Health Research Council
Nepal: Institutional Review Committee, Kanti Children's Hospital
United Kingdom: Research Ethics Committee

Keywords provided by University of Liverpool:
Japanese Encephalitis, Randomized Controlled Trial, intravenous immunoglobulin, safety, efficacy, Nepal

Additional relevant MeSH terms:
Encephalitis
Encephalitis, Japanese
Encephalitis, Arbovirus
Encephalitis, Viral
Central Nervous System Viral Diseases
Virus Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Infections
Arbovirus Infections
RNA Virus Infections
Flavivirus Infections
Flaviviridae Infections
Immunoglobulins
Antibodies
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014