Infant Severe Sepsis and Bacterial Meningitis in Malawi (Infaseme)

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Infant Bacterial Meningitis	Drug: Ceftriaxone v penicillin and gentamicin	Phase 4

Study Design

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	351 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	An Open Randomised Trial of Ceftriaxone v Penicillin and Gentamicin in Infant Severe Sepsis and Bacterial Meningitis in Malawi
Study Start Date :	April 2010
Actual Primary Completion Date :	February 2015
Actual Study Completion Date :	April 2015

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	up to 2 Months (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

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

Sponsors and Collaborators

University of Malawi College of Medicine

Investigators

Principal Investigator:	Elizabeth Molyneux, FRCPCH	Malawi College of Medicine, Paediatrics Department

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Elizabeth Molyneux, Professor of Paediatircs, University of Malawi College of Medicine
ClinicalTrials.gov Identifier:	NCT01247909 History of Changes
Other Study ID Numbers:	Infaseme
First Posted:	November 25, 2010
Last Update Posted:	October 26, 2016
Last Verified:	October 2016

Additional relevant MeSH terms:

Meningitis; Sepsis; Meningitis, Bacterial; Central Nervous System Diseases; Nervous System Diseases; Infection; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Central Nervous System Bacterial Infections	Bacterial Infections; Central Nervous System Infections; Gentamicins; Ceftriaxone; Penicillins; Anti-Bacterial Agents; Anti-Infective Agents; Protein Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action