Slow Initial β-lactam Infusion With High-dose Paracetamol to Improve the Outcomes of Childhood Bacterial Meningitis (INFU/PARA)
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.
|Bacterial Meningitis||Drug: Infusion with paracetamol Drug: Bolus without paracetamol||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|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.|
- Mortality [ Time Frame: On day 7 from the institution of treatment ]All patients should stay in hospital ≥7 days.
- 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.
|Actual Study Start Date:||February 2012|
|Study Completion Date:||February 2017|
|Primary Completion Date:||February 2017 (Final data collection date for primary outcome measure)|
Experimental: Infusion with paracetamol
Cefotaxime is administered as 12 hourly infusions, together with high dose paracetamol (acetaminophen)
Drug: Infusion with paracetamol
The administration of 250 mg/kg/24 hours cefotaxime during the first 4 days as continuous intravenous infusion, each single infusion lasting for 12 hours (to prevent degradation of the agent), combined with high-dose paracetamol orally; the first dose is 30 mg/kg, then 20 mg/kg every 6 hours for 4 full days.
Other Name: paracetamol=acetaminophen
Active Comparator: Bolus with placebo
Cefotaxime is administered as bolus q.i.d. with a placebo of paracetamol
Drug: Bolus without paracetamol
The control intervention consists of 250 mg/kg/24 hours cefotaxime administered traditionally with intermittent i.v. boluses and the place bo of paracetamol orally, both repeated every 6 hours (qid) for 4 days.
Other Name: Paracetamol=acetaminophen
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01540838
|Hospital Pediatrico David Bernardino|
|Study Director:||Heikki O Peltola, MD, PhD||Childrens Hospital of Helsinki University Central Hospital|