Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| SSC 1911 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of Oxford | OTHER |
| London School of Hygiene and Tropical Medicine | OTHER |
| University of Nairobi | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Amoxicillin 45mg/kg 12 hourly | Experimental |
| |
| Benzyl Penicillin 50,000IU/kg 6 hourly | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amoxicillin | Drug | Oral 45mg/kg 12 hourly |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment Failure at or Before Discharge / Day 5 Post Enrollment (Whichever Occurs First) | Treatment failure as defined in the primary outcome measure. | 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). |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kerugoya District Hospital | Kerugoya | Central | Kenya | |||
| Embu Provincial General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25550349 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Amoxicillin 45mg/kg 12 Hourly | Amoxicillin: Oral 45mg/kg 12 hourly |
| FG001 | Benzyl Penicillin 50,000IU/kg 6 Hourly | Benzyl penicillin: Intravenous 50,000IU/kg 6 hourly |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Amoxicillin | Amoxicillin 45mg/kg 12 hourly |
| BG001 | Penicillin | Benzyl penicillin 50000 IU 6 hourly |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Intention to treat analysis | Posted | Number | participants | 48 hours |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Amoxicillin | Amoxicillin 45mg/kg 12 hourly |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Congestive heart failure | Cardiac disorders | Non-systematic Assessment |
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ambrose Agweyu | KEMRI-Wellcome Trust Research Prorgamme | 254202715160 | aagweyu@kemri-wellcome.org |
Not provided
| ID | Term |
|---|---|
| D011014 | Pneumonia |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000658 | Amoxicillin |
| D010400 | Penicillin G |
| ID | Term |
|---|---|
| D000667 | Ampicillin |
| D010406 | Penicillins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Benzyl penicillin |
| Drug |
Intravenous 50,000IU/kg 6 hourly |
|
| 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 | 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. | 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. | Day 14 |
| Embu |
| Eastern |
| Kenya |
| Mbagathi District Hospital | Nairobi | Nairobi County | Kenya |
| Kisumu East District Hospital | Kisumu | Nyanza | Kenya |
| New Nyanza Provincial General Hospital | Kisumu | Nyanza | Kenya |
| Bungoma District Hospital | Bungoma | Western | Kenya |
| BG002 |
| Total |
Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 |
| Penicillin |
Benzyl penicillin 50000 IU/kg 6 hourly |
|
|
|
| Secondary | Treatment Failure at or Before Discharge / Day 5 Post Enrollment (Whichever Occurs First) | Treatment failure as defined in the primary outcome measure. | Intention to treat analysis | Posted | Number | participants | 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). |
|
|
|
|
| Secondary | Readmission With Diagnosis of Severe or Very Severe Pneumonia Within 14 Days of Enrollment | Not Posted | Day 0 to Day 14 |
| Secondary | 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. | Not Posted | Day 0 to Day 5 |
| Secondary | Outcome (Death/Readmission) at 14 Days as Determined by Telephone or Direct Interview | Definition of death as described in third secondary outcome measure. | Posted | Number | participants | Day 14 |
|
|
|
|
| 1 |
| 263 |
| 0 |
| 263 |
| EG001 | Benzyl Penicillin | Benzyl Penicillin 50,000IU/kg 6 hourly | 3 | 263 | 0 | 263 |
| Hypovolemic shock | Gastrointestinal disorders | Non-systematic Assessment |
|
| Renal failure | Renal and urinary disorders | Non-systematic Assessment | Acute on chronic kidney disease |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
Not provided
Not provided
| Amides |
| D009930 | Organic Chemicals |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |