Amoxicillin Versus Benzyl Penicillin for Treatment of Children Hospitalised With Severe Pneumonia

KEMRI-Wellcome Trust

Status and phase

Completed

Phase 3

Conditions

Pneumonia

Treatments

Drug: Amoxicillin

Drug: Benzyl penicillin

Study type

Interventional

Funder types

Other

Identifiers

NCT01399723

KEMRI_CT_2010/0014

SSC 1911

Details and patient eligibility

About

This study seeks to determine whether clinical outcome following initial treatment of severe pneumonia with oral amoxicillin is as effective as the current standard benzyl penicillin. The study will also provide an estimate of the proportion of Kenyan children with severe pneumonia who fail treatment with a single antibiotic.

Full description

Case management for the treatment of childhood acute respiratory infections has been widely promoted in many developing countries for over 20 years. Despite this, pneumonia continues to claim over 1.5 million lives of children under five annually. The use of affordable, easily-administered, safe, effective treatments can potentially reduce the burden of childhood pneumonia. The WHO recommends the use of a single antibiotic for the treatment of severe pneumonia. Whereas in Asia, evidence from large randomized clinical trials has changed policy recommendations for treatment of severe pneumonia from parenteral penicillin to oral amoxicillin, there is little evidence to inform a similar move in African children where pneumonia is associated with poorer outcomes. In this study the investigators will investigate effectiveness of oral amoxicillin versus the current standard treatment, benzyl penicillin in severe childhood pneumonia using a randomized controlled non-inferiority design preceded by a pilot pre-intervention phase. The investigators will also collect observational data HIV-exposed / infected children with severe pneumonia. 594 children aged 2 - 59 months admitted with clinical signs of severe pneumonia to up to 7 hospitals in Kenya will be randomly assigned to receive either oral amoxicillin or injectable benzyl penicillin. They will then be followed up for the primary outcome of pre-defined treatment failure at 48 hours. The results of this trial will provide valuable data on the effectiveness of oral amoxicillin in the treatment of severe pneumonia in a population of Kenyan children and determine the practicability of conducting large pragmatic trials on pneumonia in Africa similar to those done in Asia.

Enrollment

561 patients

Sex

All

Ages

2 to 59 months old

Volunteers

No Healthy Volunteers

Inclusion criteria

Clinical signs of WHO-defined severe pneumonia
Age 2 months to 59 months

Exclusion criteria

Clinical signs of WHO-defined very severe pneumonia
Clinical or laboratory diagnosis of meningitis
Clinical diagnosis of severe malnutrition (marasmus/kwashiorkor)
Clinical or laboratory diagnosis of severe anaemia requiring transfusion
HIV-exposure on rapid HIV antibody test (only observational data will be collected from these patients)
Elimination of signs of severe pneumonia in a child with wheeze after outpatient bronchodilator therapy
Chronic condition that may underlie or contribute to a presentation with respiratory distress such as: known chronic renal or cardiac disease, presence of cerebral palsy predisposing child to aspiration/hypostatic pneumonia
Established bronchiectasis or congenital abnormality of the lower respiratory tract
Upper airway obstruction producing stridor
Admission from outpatient clinic specifically for treatment of TB
Referral from another inpatient facility following treatment with injectable antibiotics for more than 24 hours or because the initial regimen is considered to have failed
Documented history of >48hours treatment with oral amoxicillin
Failure to obtain informed consent
Penicillin allergy