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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Slow Initial β-lactam Infusion With High-dose Paracetamol to Improve the Outcomes of Childhood Bacterial Meningitis, Especially of Pneumococcal Meningitis, in Angola.

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 Summary:

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.


Sponsor: Helsinki University

Current Primary Outcome: Mortality [ Time Frame: On day 7 from the institution of treatment ]

All patients should stay in hospital ≥7 days.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Mortality [ Time Frame: On days 14, 21, and 28 from the institution of treatment. ]
  • Status on the modified Glasgow Outcome Scale [ Time Frame: Examined on days 7, 14, 21, and 28 since institution of treatment ]
    Scores from 5 to 1
  • Death or any sequelae [ Time Frame: Examined on days 7, 14, 21, and 28 since institution of treatment ]
    Defined as any severe neurological sequelae, or hemi- or monoparesis, or ataxia, or psychomotor retardation of any degree, or any hearing impairment. Hearing is deemed impaired if the better ear fails to detect a threshold of 40 dB. The cut-off levels for moderate and severe hearing impairment are 60 dB and 80 dB, respectively.
  • A change in hearing threshold compared to the first test result [ Time Frame: Examined on days 7, 14, 21, and 28 since instituion of treatment ]
    Hearing thresholds are determined by an independent observer on the bases of the BERA register, for each ear separately.
  • Death or severe neurological sequelae [ Time Frame: Examined on days 7, 14, 21 and 28 since institution of treatment ]
    Severe neurological sequelae are defined as blindness, tetraplegia/paresia, hydrocephalus requiering a shunt and severe prychomotor retardation
  • Deafness [ Time Frame: Examined on days 7, 14, 21 and 28 since initiation of treatment ]
    Defined as a hearing threshold >80dBs in the better ear.


Original Secondary Outcome: Same as current

Information By: Helsinki University

Dates:
Date Received: February 23, 2012
Date Started: February 2012
Date Completion:
Last Updated: February 26, 2017
Last Verified: February 2017