Clinical trial NCT01247909: Infant Severe Sepsis and Bacterial Meningitis in Malawi
Official title: An Open Randomised Trial of Ceftriaxone v Penicillin and Gentamicin in Infant Severe Sepsis and Bacterial Meningitis in Malawi
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infant Bacterial Meningitis
Lead sponsor: Kamuzu University of Health Sciences
Sponsor class: OTHER
First posted: 2010-11-25
Enrollment: 351
Sex: ALL
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Recovery v death or severe residual neurological sequelae at hospital discharge, 1 month and 6 months post discharge.
timeFrame: 3 years
Secondary outcomes:
measure: Outcome by causative bacterial agent, recovery v death or severe residual neurological sequelae at hospital discharge, 1 month and 6 months post discharge.
timeFrame: 3 years
Other outcomes:
Locations:
city: Private Bag 360 Blantyre
country: Malawi
facility: Queen Elizabeth Central Hospital/ College of Medicne
Study officials:
affiliation: Malawi College of Medicine, Paediatrics Department
name: Elizabeth Molyneux, FRCPCH
role: PRINCIPAL_INVESTIGATOR
References: