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

NCT01540838 | Completed Phase 4 Results DMC

• 1 other identifier: INFU/PARA-BOLU/PLACE
• Study Type: interventional
• Target: 375
• Locations: 1 country
• Sites: 1

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.

Conditions

Bacterial Meningitis

Keywords

Bacterial meningitis; infusion; bolus; paracetamol

Outcome Measures

Primary Outcomes (1)

• Day 7 Mortality

  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.

  On day 7 from the institution of treatment

Secondary Outcomes (8)

• 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.

• 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.

• Death or Any Neurological Sequelae on Day 7

  Examined on day 7 since institution of treatment.

• 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.

• Death or Severe Neurological Sequelae on Day 7

  Examined on day 7 since institution of treatment

Study Arms (2)

Infusion with paracetamol

EXPERIMENTAL

Cefotaxime is administered as 12 hourly infusions, together with high dose paracetamol (acetaminophen)

Drug: Infusion with paracetamol

Bolus with placebo

ACTIVE COMPARATOR

Cefotaxime is administered as bolus q.i.d. with a placebo of paracetamol

Drug: Bolus without paracetamol

Interventions

Infusion with paracetamol DRUG

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.

Also known as: paracetamol=acetaminophen

Infusion with paracetamol

Bolus without paracetamol DRUG

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.

Also known as: Paracetamol=acetaminophen

Bolus with placebo

Eligibility Criteria

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

You may qualify if:

• All patients whose cerebrospinal fluid (CSF) turns out to be cloudy, positive by Gram staining or latex agglutination, or shows at least 50 leukocytes per mm3, will be enrolled in the study.

You may not qualify if:

• Trauma, or relevant underlying illness such as intracranial shunt, previous neurological abnormality (cerebral palsy, Down's syndrome, meningitis)
• Previous hearing impairment (if known)
• Immunosuppression, except HIV infection
• More than one parenteral dose of a pretreatment antimicrobial. Children with oral antimicrobials are included, this information being marked in the FOLLOW-UP sheet.
• Active tuberculosis (if tuberculotic meningitis is diagnosed during trial, it will be included in intention-to-treat (ITT) analysis)
• Known hepatic disease.

Sponsors & Collaborators

• University of Helsinki: lead
• Foundation for Paediatric Research, Finland: collaborator

Study Sites (1)

Hospital Pediatrico David Bernardino

Luanda, Angola

Location

Related Publications (3)

• Pelkonen T, Roine I, Cruzeiro ML, Pitkaranta A, Kataja M, Peltola H. Slow initial beta-lactam infusion and oral paracetamol to treat childhood bacterial meningitis: a randomised, controlled trial. Lancet Infect Dis. 2011 Aug;11(8):613-21. doi: 10.1016/S1473-3099(11)70055-X. Epub 2011 May 5.

  PMID: 21550313 BACKGROUND

• Pelkonen T, Roine I, Kallio M, Jahnukainen K, Peltola H. Prevalence and significance of anaemia in childhood bacterial meningitis: a secondary analysis of prospectively collected data from clinical trials in Finland, Latin America and Angola. BMJ Open. 2022 Mar 14;12(3):e057285. doi: 10.1136/bmjopen-2021-057285.

  PMID: 35288394 DERIVED

• Savonius O, Rugemalira E, Roine I, Cruzeiro ML, Peltola H, Pelkonen T. Extended Continuous beta-Lactam Infusion With Oral Acetaminophen in Childhood Bacterial Meningitis: A Randomized, Double-blind Clinical Trial. Clin Infect Dis. 2021 May 18;72(10):1738-1744. doi: 10.1093/cid/ciaa341.

  PMID: 32246138 DERIVED

MeSH Terms

Conditions

Meningitis, Bacterial

Interventions

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)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: Dr. Okko Savonius, PhD candidate
• Organization: University of Helsinki, Children´s Hospital, Helsinki University Hospital

okko.savonius@helsinki.fi

+358456731185

Study Officials

• Heikki O Peltola, MD, PhD

  Childrens Hospital of Helsinki University Central Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Profesor

Study Record Dates

• First Submitted: February 23, 2012
• First Posted: February 29, 2012
• Study Start: February 1, 2012
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: September 24, 2019
• Results First Posted: September 24, 2019

Record last verified: 2019-09

Locations

AN (1)