A Phase 3 interventional study of Amoxicillin and Benzyl penicillin in Pneumonia, sponsored by KEMRI-Wellcome Trust Collaborative Research Program. Completed at 6 sites in Kenya. Open to participants aged 2 Months to 59 Months. Per ClinicalTrials.gov, last updated 2015-02-13.
Sponsored by KEMRI-Wellcome Trust Collaborative Research Program · Phase 3, Interventional, and Treatment
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.
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.
Exclusion Criteria:
Drug: Amoxicillin
Drug: Benzyl penicillin
Oral 45mg/kg 12 hourly
Intravenous 50,000IU/kg 6 hourly
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
Time frame: 48 hours
Treatment Failure at or Before Discharge / Day 5 Post Enrollment (Whichever Occurs First)
Treatment failure as defined in the primary outcome measure.
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).
Readmission With Diagnosis of Severe or Very Severe Pneumonia Within 14 Days of Enrollment
Time frame: Day 0 to Day 14
Death at or Before Five Days Following Enrollment
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.
Time frame: Day 0 to Day 5
Outcome (Death/Readmission) at 14 Days as Determined by Telephone or Direct Interview
Definition of death as described in third secondary outcome measure.
Time frame: Day 14
| Milestone | Amoxicillin 45mg/kg 12 Hourly | Benzyl Penicillin 50,000IU/kg 6 Hourly |
|---|---|---|
| Started | 263 | 264 |
| Completed | 263 | 263 |
| Not completed | 0 | 1 |
| Withdrew: Lost to follow-up | 0 | 1 |
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
| participants | Amoxicillin | Penicillin |
|---|---|---|
| Treatment Failure at 48 Hours (Two Full Days After Enrollment) | 20 | 21 |
Treatment failure as defined in the primary outcome measure.
| participants | Amoxicillin | Penicillin |
|---|---|---|
| Treatment Failure at or Before Discharge / Day 5 Post Enrollment (Whichever Occurs First) | 30 | 29 |
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
Definition of death as described in third secondary outcome measure.
| participants | Amoxicillin | Penicillin |
|---|---|---|
| Outcome (Death/Readmission) at 14 Days as Determined by Telephone or Direct Interview | 33 | 42 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Amoxicillin | — | 1/263 (0.4%) | 0/263 (0%) |
| Benzyl Penicillin | — | 3/263 (1.1%) | 0/263 (0%) |
| Event | Amoxicillin | Benzyl Penicillin |
|---|---|---|
| Congestive heart failureCardiac disorders | 1/263 | 0/263 |
| Hypovolemic shockGastrointestinal disorders | 0/263 | 1/263 |
| Renal failureRenal and urinary disorders | 0/263 | 1/263 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 0/263 | 1/263 |
| Age, Continuous(years) | Amoxicillin | Penicillin | Total |
|---|---|---|---|
| Median | 14 (7 to 25) | 13 (7 to 24) | 13 (7 to 24) |
| Sex: Female, Male(Participants) | Amoxicillin | Penicillin | Total |
|---|---|---|---|
| Female | 120 | 106 | 226 |
| Male | 143 | 158 | 301 |
| Region of Enrollment(participants) | Amoxicillin | Penicillin | Total |
|---|---|---|---|
| Kenya | 263 | 264 | 527 |
This study is completed, as verified in Jan 2015. You cannot join it, but the record below documents what was studied.
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KEMRI-Wellcome Trust Collaborative Research Program