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

NCT01399723 | Completed Phase 3 Results DMC

• 2 other identifiers: KEMRI_CT_2010/0014SSC 1911
• Study Type: interventional
• Target: 561
• Locations: 1 country
• Sites: 6

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.

Conditions

Pneumonia

Keywords

Severe pneumonia

Outcome Measures

Primary Outcomes (1)

• Treatment Failure at 48 Hours (Two Full Days After Enrollment)

  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

  48 hours

Secondary Outcomes (4)

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

  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).

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

  Day 0 to Day 14

• Death at or Before Five Days Following Enrollment

  Day 0 to Day 5

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

  Day 14

Study Arms (2)

Amoxicillin 45mg/kg 12 hourly

EXPERIMENTAL

Drug: Amoxicillin

Benzyl Penicillin 50,000IU/kg 6 hourly

ACTIVE COMPARATOR

Drug: Benzyl penicillin

Interventions

Amoxicillin DRUG

Oral 45mg/kg 12 hourly

Amoxicillin 45mg/kg 12 hourly

Benzyl penicillin DRUG

Intravenous 50,000IU/kg 6 hourly

Benzyl Penicillin 50,000IU/kg 6 hourly

Eligibility Criteria

• Age: 2 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• KEMRI-Wellcome Trust Collaborative Research Program: lead
• University of Oxford: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• University of Nairobi: collaborator

Study Sites (6)

Kerugoya District Hospital

Kerugoya, Central, Kenya

Location

Embu Provincial General Hospital

Embu, Eastern, Kenya

Location

Mbagathi District Hospital

Nairobi, Nairobi County, Kenya

Location

Kisumu East District Hospital

Kisumu, Nyanza, Kenya

Location

New Nyanza Provincial General Hospital

Kisumu, Nyanza, Kenya

Location

Bungoma District Hospital

Bungoma, Western, Kenya

Location

Related Publications (1)

• 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.

  PMID: 25550349 DERIVED

MeSH Terms

Conditions

Pneumonia

Interventions

Amoxicillin; Penicillin G

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Ambrose Agweyu
• Organization: KEMRI-Wellcome Trust Research Prorgamme

aagweyu@kemri-wellcome.org

254202715160

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2011
• First Posted: July 22, 2011
• Study Start: September 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: February 13, 2015
• Results First Posted: February 13, 2015

Record last verified: 2015-01

Locations

KE (6)