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

Condition(s) targeted: Pneumonia

Intervention: Amoxicillin (Drug); Benzyl penicillin (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: KEMRI-Wellcome Trust Collaborative Research Program

Official(s) and/or principal investigator(s):
Ambrose Agweyu, MSc, Principal Investigator, Affiliation: Kemri- Wellcome Trust Research Programme, Nairobi, Kenya
Elizabeth Obimbo, MMed, Principal Investigator, Affiliation: Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya
Roma Chilengi, MD, Principal Investigator, Affiliation: Centre for Infectious Disease Research, Zambia
Tansy Edwards, MSc, Principal Investigator, Affiliation: London School of Hygiene and Tropical Medicine
Mike English, MD, Principal Investigator, Affiliation: Kemri - Wellcome Trust Research Programme, Nairobi, Kenya

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.

Official title: Amoxicillin Versus Benzyl Penicillin for Severe Childhood Pneumonia Amongst Inpatients: An Open Label Randomised Controlled Non-inferiority Trial

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Treatment Failure at 48 Hours (Two Full Days After Enrollment)

Secondary outcome:

Treatment Failure at or Before Discharge / Day 5 Post Enrollment (Whichever Occurs First)

Readmission With Diagnosis of Severe or Very Severe Pneumonia Within 14 Days of Enrollment

Death at or Before Five Days Following Enrollment

Outcome (Death/Readmission) at 14 Days as Determined by Telephone or Direct Interview

Detailed 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.

Minimum age: 2 Months. Maximum age: 59 Months. Gender(s): Both.

Criteria:

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

Mbagathi District Hospital, Nairobi, Kenya

Kerugoya District Hospital, Kerugoya, Central, Kenya

Embu Provincial General Hospital, Embu, Eastern, Kenya

Kisumu East District Hospital, Kisumu, Nyanza, Kenya

New Nyanza Provincial General Hospital, Kisumu, Nyanza, Kenya

Bungoma District Hospital, Bungoma, Western, Kenya

Starting date: September 2011
Last updated: January 28, 2015