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

NCT00619203 | Completed Phase 3

• 1 other identifier: P.03/07/499
• Study Type: interventional
• Target: 466
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Bacterial meningitis; glycerol; high dose paracetamol; children

Outcome Measures

Primary Outcomes (1)

• Primary end points are death, severe neurological sequelae, hearing loss.

  2008-2011

Secondary Outcomes (1)

• Secondary end points are audiological or neurological sequelae (according to the Denver-II developmental screening test).

  2008-2011

Study Arms (4)

A

ACTIVE COMPARATOR

Two active ingredients

Drug: Glycerol and paracetamol; Drug: Paracetamol and glycerol

B

ACTIVE COMPARATOR

One active ingredient

Drug: Paracetamol; Drug: Glycerol

C

ACTIVE COMPARATOR

One (other) active ingredient

Drug: Paracetamol

D

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Glycerol and paracetamol DRUG

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

A

Paracetamol DRUG

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

B

Placebo DRUG

2 placebos, one po, one suppository

D

Paracetamol and glycerol DRUG

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

A

Glycerol DRUG

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

B

Eligibility Criteria

• Age: 2 Months - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kamuzu University of Health Sciences: lead

Study Sites (1)

College of Medicine, Queen Elizabeth Central Hospital

Blantyre, 3, Malawi

Location

MeSH Terms

Conditions

Meningitis, Bacterial

Interventions

Glycerol; Acetaminophen

Condition Hierarchy (Ancestors)

Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Triose Sugar Alcohols; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Acetanilides; Anilides; Amides; Aniline Compounds; Amines

Study Officials

• Elizabeth M Molyneux, FRCPCH

  College of Medicine, Blantyre, Malawi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Paediatircs

Study Record Dates

• First Submitted: February 7, 2008
• First Posted: February 20, 2008
• Study Start: March 1, 2008
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: July 10, 2012

Record last verified: 2012-07

Locations

MA (1)