Trial record 19 of 333 for:    meningitis

Oral Glycerol and High-Dose Rectal Paracetamol to Improve the Prognosis of Childhood Bacterial Meningitis (GLYIP)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Elizabeth Molyneux, University of Malawi College of Medicine
ClinicalTrials.gov Identifier:
NCT00619203
First received: February 7, 2008
Last updated: July 9, 2012
Last verified: July 2012
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 ]

Enrollment: 466
Study Start Date: March 2008
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
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

Active Comparator: B
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
Active Comparator: C
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
Placebo Comparator: D 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00619203

Locations
Malawi
College of Medicine, Queen Elizabeth Central Hospital
Blantyre, Malawi, 3
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: Elizabeth Molyneux, Professor of Paediatircs, University of Malawi College of Medicine
ClinicalTrials.gov Identifier: NCT00619203     History of Changes
Other Study ID Numbers: P.03/07/499
Study First Received: February 7, 2008
Last Updated: July 9, 2012
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:
Meningitis
Meningitis, Bacterial
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Bacterial Infections
Bacterial Infections
Acetaminophen
Glycerol
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Cryoprotective Agents
Protective Agents

ClinicalTrials.gov processed this record on July 20, 2014