Infant Severe Sepsis and Bacterial Meningitis in Malawi (Infaseme)

An Open Randomised Trial of Ceftriaxone v Penicillin and Gentamicin in Infant Severe Sepsis and Bacterial Meningitis in Malawi

This study aims to improve the outcome of infants (<2 months) with severe sepsis and meningitis at the Queen Elizabeth Central Hospital, Blantyre, Malawi.

Currently WHO recommends the treatment of infant severe sepsis and bacterial meningitis with 14 to 21 day course of penicillin and gentamicin as first line. The second line treatment is cefotaxime or ceftriaxone.

Severe bacterial infections are common in infants under 2 months of age and the mortality is very high (~50%). There are several reasons for this; one is that the first line antibiotics used are no longer as effective as they used to be. Bacterial resistance to the first line antibiotics has increased and some infections especially of the central nervous system may only be partly treated and not eradicated by present therapy. First line treatment is cheap and available but requires 4 injections a day, for at least 14 days, a total of 58 injections. Many mothers find this number too much and abscond. The investigators second line therapy is ceftriaxone which is also available and cheap and the advantage of being given as a daily injection. The disadvantage is that it can cause (reversible) jaundice particularly in premature babies and it must not be given with calcium products. The investigators do not give calcium to the investigators infants as the investigators cannot routinely check electrolytes. All the most common causes of bacterial meningitis in this age group in the investigators setting are sensitive to ceftriaxone.

The investigators wish to undertake an open randomized trial of penicillin and gentamicin v ceftriaxone as first line treatment for infant meningitis. The investigators are able to monitor for side effects.

The investigators hypothesise that the ceftriaxone arm will have 20% less deaths that the penicillin and gentamicin group.

Study Overview

• Status: Completed
• Conditions: Infant Bacterial Meningitis
• Intervention / Treatment: Drug: Ceftriaxone v penicillin and gentamicin

• Study Type: Interventional
• Enrollment (Actual): 351
• Phase: Phase 4

Contacts and Locations

Study Locations

• Malawi
  • Private Bag 360 Blantyre, Malawi, 3
    • Queen Elizabeth Central Hospital/ College of Medicne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children less than 2 months
• Suspicion of bacterial meningitis
• Parental/guardian informed consent

Exclusion Criteria:

• Infant with hyperbilirubinaemia
• Infant requiring calcium
• Infant know to be hypersensitive to any of the three drugs
• Infant who has been an inpatient for more than 72 hours
• Infant with congenital central nervous system abnormalities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ceftriaxone; Ceftriaxone in infants with sepsis and bacterial meningitis	Drug: Ceftriaxone v penicillin and gentamicin; Ceftriaxone v the standard treatment of infant meningitis (penicillin and gentamicin). Ceftriaxone will be given at a dose of 80mg/kg once a day for at least 14 days.
Active Comparator: Penicillin and gentamicin; Penicillin and Gentamicin in infants with sepsis and bacterial meningitis	Drug: Ceftriaxone v penicillin and gentamicin; Ceftriaxone v the standard treatment of infant meningitis (penicillin and gentamicin). Ceftriaxone will be given at a dose of 80mg/kg once a day for at least 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recovery v death or severe residual neurological sequelae at hospital discharge, 1 month and 6 months post discharge.	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Outcome by causative bacterial agent, recovery v death or severe residual neurological sequelae at hospital discharge, 1 month and 6 months post discharge.	3 years

Collaborators and Investigators

• Sponsor: Kamuzu University of Health Sciences
• Investigators: Principal Investigator: Elizabeth Molyneux, FRCPCH, Malawi College of Medicine, Paediatrics Department

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: January 14, 2010
• First Submitted That Met QC Criteria: November 24, 2010
• First Posted (Estimate): November 25, 2010

Study Record Updates

• Last Update Posted (Estimate): October 26, 2016
• Last Update Submitted That Met QC Criteria: October 24, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Central Nervous System Infections; Bacterial Infections; Bacterial Infections and Mycoses; Central Nervous System Bacterial Infections; Sepsis; Meningitis; Meningitis, Bacterial; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Ceftriaxone; Gentamicins; Penicillins
• Other Study ID Numbers: Infaseme