Clinical trial NCT01399723: Amoxicillin Versus Benzyl Penicillin for Treatment of Children Hospitalised With Severe Pneumonia
Official title: Amoxicillin Versus Benzyl Penicillin for Severe Childhood Pneumonia Amongst Inpatients: An Open Label Randomised Controlled Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia
Keywords: Severe pneumonia
Lead sponsor: KEMRI-Wellcome Trust Collaborative Research Program
Sponsor class: OTHER
Collaborators: name: University of Oxford
name: London School of Hygiene and Tropical Medicine
name: University of Nairobi
First posted: 2011-07-22
Enrollment: 561
Sex: ALL
Minimum age (years): 2
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
measure: Treatment Failure at 48 Hours (Two Full Days After Enrollment)
timeFrame: 48 hours
Secondary outcomes:
measure: Treatment Failure at or Before Discharge / Day 5 Post Enrollment (Whichever Occurs First)
timeFrame: Patients will be followed up from the day of hospitalisation (day 0) until the day of medical discharge (average duration of 3 days) or until day 5 of hospitalisation (whichever occurs first).
measure: Readmission With Diagnosis of Severe or Very Severe Pneumonia Within 14 Days of Enrollment
timeFrame: Day 0 to Day 14
measure: Death at or Before Five Days Following Enrollment
timeFrame: Day 0 to Day 5
measure: Outcome (Death/Readmission) at 14 Days as Determined by Telephone or Direct Interview
timeFrame: Day 14
Other outcomes:
Locations:
city: Kerugoya
country: Kenya
facility: Kerugoya District Hospital
state: Central
city: Embu
country: Kenya
facility: Embu Provincial General Hospital
state: Eastern
city: Kisumu
country: Kenya
facility: Kisumu East District Hospital
state: Nyanza
city: Kisumu
country: Kenya
facility: New Nyanza Provincial General Hospital
state: Nyanza
city: Bungoma
country: Kenya
facility: Bungoma District Hospital
state: Western
city: Nairobi
country: Kenya
facility: Mbagathi District Hospital
Study officials:
affiliation: Kemri- Wellcome Trust Research Programme, Nairobi, Kenya
name: Ambrose Agweyu, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya
name: Elizabeth Obimbo, MMed
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for Infectious Disease Research, Zambia
name: Roma Chilengi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: London School of Hygiene and Tropical Medicine
name: Tansy Edwards, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Kemri - Wellcome Trust Research Programme, Nairobi, Kenya
name: Mike English, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Agweyu A, Gathara D, Oliwa J, Muinga N, Edwards T, Allen E, Maleche-Obimbo E, English M; Severe Pneumonia Study Group. Oral amoxicillin versus benzyl penicillin for severe pneumonia among kenyan children: a pragmatic randomized controlled noninferiority trial. Clin Infect Dis. 2015 Apr 15;60(8):1216-24. doi: 10.1093/cid/ciu1166. Epub 2014 Dec 30.