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

This study has been completed.
Sponsor:
Collaborators:
University of Oxford
London School of Hygiene and Tropical Medicine
University of Nairobi
Information provided by (Responsible Party):
KEMRI-Wellcome Trust Collaborative Research Program
ClinicalTrials.gov Identifier:
NCT01399723
First received: July 12, 2011
Last updated: November 22, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Pneumonia
Drug: Amoxicillin
Drug: Benzyl penicillin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by KEMRI-Wellcome Trust Collaborative Research Program:

Primary Outcome Measures:
  • Treatment failure at 48 hours (two full days after enrollment) [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    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:
  • 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). ] [ Designated as safety issue: No ]
    Treatment failure as defined in the primary outcome measure.

  • Readmission with diagnosis of severe or very severe pneumonia within 14 days of enrollment [ Time Frame: Day 0 to Day 14 ] [ Designated as safety issue: No ]
  • Death at or before five days following enrollment [ Time Frame: Day 0 to Day 5 ] [ Designated as safety issue: No ]
    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.

  • Outcome (death/readmission) at 14 days as determined by telephone or direct interview [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    Definition of death as described in third secondary outcome measure.


Enrollment: 561
Study Start Date: September 2011
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   2 Months to 59 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01399723

Locations
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
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
Investigators
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
  More Information

No publications provided

Responsible Party: KEMRI-Wellcome Trust Collaborative Research Program
ClinicalTrials.gov Identifier: NCT01399723     History of Changes
Other Study ID Numbers: KEMRI_CT_2010/0014, SSC 1911
Study First Received: July 12, 2011
Last Updated: November 22, 2013
Health Authority: Kenya: Pharmacy and Poisons Board

Keywords provided by KEMRI-Wellcome Trust Collaborative Research Program:
Severe pneumonia

Additional relevant MeSH terms:
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Amoxicillin
Penicillin G
Penicillin G Benzathine
Penicillin G Procaine
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014