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

Summary

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.

Conditions

• Bacterial Meningitis

Interventions

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

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

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

DRUG

Placebo

2 placebos, one po, one suppository

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

DRUG

Glycerol

glycerol 1.5 ml/kg /dose 6 hourly x 8 max dose = 25ml

Sponsors & Collaborators

• Kamuzu University of Health Sciences

  lead OTHER

Principal Investigators

• Elizabeth M Molyneux, FRCPCH · College of Medicine, Blantyre, Malawi

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

FACTORIAL

Eligibility

Min Age

2 Months

Max Age

15 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-03-31

Primary Completion

2012-03-31

Completion

2012-03-31

Countries

• Malawi

Study Locations