Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01399723
Recruitment Status : Completed
First Posted : July 22, 2011
Results First Posted : February 13, 2015
Last Update Posted : February 13, 2015
University of Oxford
London School of Hygiene and Tropical Medicine
University of Nairobi
Information provided by (Responsible Party):
KEMRI-Wellcome Trust Collaborative Research Program

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.

Condition or disease Intervention/treatment Phase
Pneumonia Drug: Amoxicillin Drug: Benzyl penicillin Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 561 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Amoxicillin Versus Benzyl Penicillin for Severe Childhood Pneumonia Amongst Inpatients: An Open Label Randomised Controlled Non-inferiority Trial
Study Start Date : September 2011
Actual Primary Completion Date : September 2013
Actual Study Completion Date : September 2013

Arm Intervention/treatment
Experimental: Amoxicillin 45mg/kg 12 hourly Drug: Amoxicillin
Oral 45mg/kg 12 hourly

Active Comparator: Benzyl Penicillin 50,000IU/kg 6 hourly Drug: Benzyl penicillin
Intravenous 50,000IU/kg 6 hourly

Primary Outcome Measures :
  1. Treatment Failure at 48 Hours (Two Full Days After Enrollment) [ Time Frame: 48 hours ]
    Development of any signs of very severe pneumonia at any time Hypoxemia defined as SpO2 <85% or <80% for altitude < or ≥1500m respectively measured after minimum of 3 minutes on ambient air Persistent vomiting (occurring within 30 minutes of administration of amoxicillin with failure to retain drug after 3 successive attempts at administration) at any time Clinical diagnosis of new bacterial co-morbid condition requiring revision of antibiotic treatment at any time Lower chest wall indrawing Temperature ≥38◦C Respiratory rate ≥5bpm of admission rate if above age-adjusted normal upper limit

Secondary Outcome Measures :
  1. Treatment Failure at or Before Discharge / Day 5 Post Enrollment (Whichever Occurs First) [ Time Frame: 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). ]
    Treatment failure as defined in the primary outcome measure.

  2. Readmission With Diagnosis of Severe or Very Severe Pneumonia Within 14 Days of Enrollment [ Time Frame: Day 0 to Day 14 ]
  3. Death at or Before Five Days Following Enrollment [ Time Frame: Day 0 to Day 5 ]
    Death defined as: in-hospital death occurring at any time after randomisation (recruitment for HIV-exposed participants) or verbal report of death of the enrolled patient from parent/guardian communicated either directly or via telephone conversation.

  4. Outcome (Death/Readmission) at 14 Days as Determined by Telephone or Direct Interview [ Time Frame: Day 14 ]
    Definition of death as described in third secondary outcome measure.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   2 Months to 59 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01399723

Layout table for location information
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
Mbagathi District Hospital
Nairobi, Kenya
Sponsors and Collaborators
KEMRI-Wellcome Trust Collaborative Research Program
University of Oxford
London School of Hygiene and Tropical Medicine
University of Nairobi
Layout table for investigator information
Principal Investigator: Ambrose Agweyu, MSc Kemri- Wellcome Trust Research Programme, Nairobi, Kenya
Principal Investigator: Elizabeth Obimbo, MMed Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya
Principal Investigator: Roma Chilengi, MD Centre for Infectious Disease Research, Zambia
Principal Investigator: Tansy Edwards, MSc London School of Hygiene and Tropical Medicine
Principal Investigator: Mike English, MD Kemri - Wellcome Trust Research Programme, Nairobi, Kenya
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: KEMRI-Wellcome Trust Collaborative Research Program Identifier: NCT01399723    
Other Study ID Numbers: KEMRI_CT_2010/0014
SSC 1911
First Posted: July 22, 2011    Key Record Dates
Results First Posted: February 13, 2015
Last Update Posted: February 13, 2015
Last Verified: January 2015
Keywords provided by KEMRI-Wellcome Trust Collaborative Research Program:
Severe pneumonia
Additional relevant MeSH terms:
Layout table for MeSH terms
Respiratory Tract Infections
Lung Diseases
Respiratory Tract Diseases
Penicillin G
Penicillin G Benzathine
Penicillin G Procaine
Anti-Bacterial Agents
Anti-Infective Agents