Slow Initial β-lactam Infusion With High-dose Paracetamol to Improve the Outcomes of Childhood Bacterial Meningitis

Phase 4

Completed

Conditions: Bacterial Meningitis

Interventions: Drug: Bolus without paracetamol
Drug: Infusion with paracetamol

Registration Number: NCT01540838

Lead Sponsor: University of Helsinki

Brief Summary: The main purpose of this trial is to test if mortality of childhood bacterial meningitis can be reduced by slow, continuous infusion of cefotaxime initially, instead of the traditional bolus administration four times daily (qid), combined with high-dose paracetamol orally, when both treatments are executed for the first 4 days. The series will be collected at Hospital Pediátrico David Bernardino, Luanda, Angola.

The recruitment of patients begins, the conditions permitting, in early 2012. The criteria for patient participation is a child at the age of 2 months to 15 years who presents with the symptoms and signs suggestive of bacterial meningitis, for whom a lumbar puncture is performed, and the cerebrospinal fluid analysis suggests bacterial meningitis.

Detailed Description: The principal objective of the study is to examine if mortality of childhood bacterial meningitis can be reduced by slow continuous infusion of cefotaxime combined with high-dose paracetamol orally for the first 4 days (instead of the traditional qid administration of cefotaxime without concomitant paracetamol). Children qualifying for entry (see criteria below), whose guardian has given informed consent,will be randomized into 2 treatment arms (see details below)and receive the treatments in a double blind fashion (see details below). Primary and secondary outcomes (detailed below) will be evaluated according to predefined criteria and time points (see below).

Results will be analyzed for all patients in ITT datasets and in prespecified subgroups (etiology, nutritional status, etc.) in both crude and adjusted analysis. The efficacy results will be expressed as OR with 95% confidence intervals.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 375

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bolus with placebo	Bolus without paracetamol	Cefotaxime is administered as bolus q.i.d. with a placebo of paracetamol
Infusion with paracetamol	Infusion with paracetamol	Cefotaxime is administered as 12 hourly infusions, together with high dose paracetamol (acetaminophen)

Primary Outcome Measures

Name	Time	Method
Day 7 Mortality	On day 7 from the institution of treatment	All patients who had received at least one dose of treatment and were dead on day 7 from the institution of treatment on day 1.

Secondary Outcome Measures

Name	Time	Method
All Deaths During Hospital Stay	The outcome was assessed each day until the patient was discharged from the hospital. The longest hospital stay was 84 days, while the last death occurred 39 days after treatment initiation.	All patients who had received at least one dose of treatment and died during the hospital stay.
Status on the Modified Glasgow Outcome Scale	Examined at discharge from hospital, except for hearing evaluations which were performed at earliest seven days since the institution of treatment, during the hospital stay. The longest hospital stay was 84 days.	Scores on the modified Glasgow Outcome Scale which range from a maximum of 5 (best) to a minimum of 1 (worst) points. The Glasgow Outcome Scale categorizes the outcome after brain injury into five categories, based on the level and severeness of disability. As hearing impairment is one of the most common sequelae of bacterial meningitis, an assessment of hearing should be included when estimating the grade of disability. Hearing thresholds (in decibel, dB) were determined by brainstem evoked response audiometry (BERA), for each ear separately.
Death or Any Neurological Sequelae on Day 7	Examined on day 7 since institution of treatment.	Defined as death or any severe neurological sequelae, or hemi- or monoparesis, or ataxia, or psychomotor retardation of any degree.
A Change in Hearing Threshold Compared to the First Test Result	Hearing thresholds obtained during any of the first three days after hospital admission were compared with hearing thresholds obtained on day seven or later, during the hospital stay. The longest hospital stay was 84 days.	Hearing thresholds (in decibel, dB) were determined by brainstem evoked response audiometry (BERA), for each ear separately. The better ear's hearing threshold, obtained on admission or shortly thereafter, was compared with the better ear's hearing threshold obtained at earliest after one week of treatment.
Death or Severe Neurological Sequelae on Day 7	Examined on day 7 since institution of treatment	Death or severe neurological sequelae, defined as blindness, tetraplegia/paresis, hydrocephalus requiring a shunt and severe psychomotor retardation
Number of Participants With Deafness	This outcome includes hearing thresholds determined at earliest seven days after the institution of treatment, during the hospital stay. The longest hospital stay was 84 days.	Hearing thresholds (in decibel, dB) were determined by brainstem evoked response audiometry (BERA), for each ear separately. Deafness was defined as a hearing threshold \>80 dB in the better ear.
Death or Any Neurological Sequelae at Discharge From Hospital.	Examined at discharge from hospital. The longest hospital stay was 84 days.	Defined as death or any severe neurological sequelae, or hemi- or monoparesis, or ataxia, or psychomotor retardation of any degree.
Death or Severe Neurological Sequelae at Discharge	Examined at discharge from hospital. The longest hospital stay was 84 days.	Death or severe neurological sequelae, defined as blindness, tetraplegia/paresis, hydrocephalus requiring a shunt and severe psychomotor retardation