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Oral Glycerol and High-Dose Rectal Paracetamol to Improve the Prognosis of Childhood Bacterial Meningitis (GLYIP)
This study is currently recruiting participants.
Verified by University of Malawi College of Medicine, January 2010
First Received: February 7, 2008   Last Updated: January 14, 2010   History of Changes
Sponsor: University of Malawi College of Medicine
Information provided by: University of Malawi College of Medicine
ClinicalTrials.gov Identifier: NCT00619203
  Purpose

Bacterial meningitis remains a significant cause of morbidity and mortality in children, especially in countries with limited resources. Efforts to improve the grim outcome have included altering the first line antibiotic therapy, controlling seizures and managing fluids more carefully. Adjuvant therapy of steroids has been used with limited success in children in the West and with no proven value in Malawi and other resource constrained settings. Glycerol has been used to reduce brain oedema in neurosurgery and it has recently been shown to reduce morbidity in childhood meningitis in South America. Paracetamol in a high dosage has been shown to reduce inflammation and cytokine levels in septicaemia with improved outcomes in adults.

In Malawi the investigators have tried adjuvant steroids with no improvement in outcome of childhood meningitis. They have recently concluded a study of ceftriaxone which has shown no improvement in mortality though there is less hearing loss than with chloramphenicol and benzyl penicillin.

Following the encouraging results of the Childhood South American Study it is important to assess the use of adjuvant glycerol in children in the investigators' setting. Paracetamol is routinely used in meningitis because of the accompanying fever and headache. This is an opportunity to study its place as adjuvant therapy more carefully than has previously been done.

The investigators propose a prospective, randomized, double blind 2 by 2 factorial designed study to assess the advantage of ceftriaxone (antibiotic) given with paracetamol and glycerol in combination, singly or with neither adjuvant therapy in childhood bacterial meningitis.


Condition Intervention Phase
Bacterial Meningitis
Drug: Glycerol and paracetamol
Drug: Paracetamol
Drug: Placebo
Drug: Paracetamol and glycerol
Drug: Glycerol
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment, Efficacy Study
Official Title: Oral Glycerol and High-Dose Rectal Paracetamol to Improve the Prognosis of Childhood Bacterial Meningitis - A Prospective, Randomized, and Double-Blind Clinical Study Using a Two-by-Two Factorial Design

Resource links provided by NLM:


Further study details as provided by University of Malawi College of Medicine:

Primary Outcome Measures:
  • Primary end points are death, severe neurological sequelae, hearing loss. [ Time Frame: 2008-2011 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Secondary end points are audiological or neurological sequelae (according to the Denver-II developmental screening test). [ Time Frame: 2008-2011 ] [ Designated as safety issue: No ]

Estimated Enrollment: 750
Study Start Date: March 2008
Estimated Study Completion Date: January 2012
Estimated Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A: Active Comparator
Two active ingredients
Drug: Glycerol and paracetamol

glycerol by mouth (po) 1.5ml/kg max 25 ml/dose x 6 hourly x 8 doses

paracetamol PR 35 mg/kg first dose, then 20 mg/kg 6 hourly x 7

Drug: Paracetamol and glycerol

35 mg/kg po first dose, then 20 mg/kg 6 hourly x 7 paracetamol

1.5 ml/kg max 25 ml/dose 6 hourly x 8 doses

B: Active Comparator
One active ingredient
Drug: Paracetamol
paracetamol 35 mg/kg first dose, then 20 mg/kg 6 hourly x 7 doses
Drug: Glycerol
glycerol 1.5 ml/kg /dose 6 hourly x 8 max dose = 25ml
C: Active Comparator
One (other) active ingredient
Drug: Paracetamol
paracetamol po 35 mg/kg first dose, then 20 mg/kg 6 hourly x 7 doses plus placebo suppository
Drug: Paracetamol
po 35 mg/kg first dose, then 20 mg/kg 6 hourly x 7 doses plus placebo suppository
D: Placebo Comparator Drug: Placebo
2 placebos, one po, one suppository

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Months to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All children aged ≥ 2 months, admitted to Queen Elizabeth Hospital, Blantyre, Malawi, with possible or confirmed acute bacterial meningitis

Exclusion Criteria:

  • Age less than two months
  • Trauma
  • Relevant underlying illness such as intracranial shunt, previous neurological disease (cerebral palsy, Down's syndrome)
  • Previous permanent hearing loss (not conductive hearing loss) if known
  • Immunosuppression except HIV infection.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00619203

Locations
Malawi
College of Medicine, Queen Elizabeth Central Hospital Recruiting
Blantyre, Malawi, 3
Contact: Elizabeth M Molyneux, FRCPCH     265 1 873 198     emolyneux@malawi.net    
Contact: E Borgstein, FRCS     265 1871 911     eborgstein@medcol.mw    
Principal Investigator: Elizabeth M Molyneux, FRCPCH            
Sponsors and Collaborators
University of Malawi College of Medicine
Investigators
Principal Investigator: Elizabeth M Molyneux, FRCPCH College of Medicine, Blantyre, Malawi
  More Information

No publications provided

Responsible Party: College of Medicine, Malawi ( Prof. Elizabeth Molyneux )
Study ID Numbers: P.03/07/499
Study First Received: February 7, 2008
Last Updated: January 14, 2010
ClinicalTrials.gov Identifier: NCT00619203     History of Changes
Health Authority: Malawi: National Health Sciences Research Committee

Keywords provided by University of Malawi College of Medicine:
Bacterial meningitis
glycerol
high dose paracetamol
children

Additional relevant MeSH terms:
Bacterial Infections
Physiological Effects of Drugs
Meningitis, Bacterial
Nervous System Diseases
Central Nervous System Diseases
Protective Agents
Cryoprotective Agents
Pharmacologic Actions
Meningitis
Glycerol
Central Nervous System Infections
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Central Nervous System Bacterial Infections
Analgesics
Peripheral Nervous System Agents
Central Nervous System Agents
Acetaminophen

ClinicalTrials.gov processed this record on February 08, 2010