Pneumonia
Conditions
Keywords
severe pneumonia, supportive care, antibiotics, World Health Organisation, intravenous fluids, nutrition, children
Brief summary
Pneumonia is one of the top causes of death in children aged below 5. More than 10% of children with severe pneumonia die. We are not sure that the currently recommended antibiotics used in children with pneumonia are the most effective. No studies have been carried out to find out whether children with pneumonia should be given intravenous (IV) fluids or nasogastric (NG) feeds. The SEARCH trial aims to find out which antibiotics and modes of feeding are the most effective in treating children with severe pneumonia and therefore helping reduce mortality.
Detailed description
Pneumonia is one of the leading causes of death among young children with more than 10% of children aged under-five with severe pneumonia dying. The World Health Organisation (WHO) guidelines recommend the use of benzyl penicillin plus gentamicin as the standard of care of treatment for severe pneumonia. However, there have been increasing concerns about the effectiveness of the current recommendations. Some authorities advise against the use of enteral nutrition in severely ill patients due to concerns of compromised respiratory status and risk of aspiration with nasogastric feeding. Evidence to support these concerns is lacking. This trial aims to find out which antibiotics are the most effective in the treatment of children with severe pneumonia by comparing the current standard of care (benzyl penicillin or ampicillin plus gentamicin) to injectable ceftriaxone and injectable amoxicillin-clavulanic acid. The study will also determine whether providing feeds through a nasogastric tube is superior to intravenous fluid therapy in children with severe pneumonia. The SEARCH trial will be a multi-site pragmatic randomised controlled trial that will assess the efficacy of both interventions in children admitted with severe pneumonia in a 3x2 factorial design. The sites will be in East Africa. Data from the trial will be used to inform policy and contribute to guidelines and improve clinical practice in settings where the burden of pneumonia is highest.
Interventions
Benzyl penicillin is a penicillin antibiotic.
Gentamicin is an aminoglycoside antibiotic.
DRUGCeftriaxone
Ceftriaxone is a third generation cephalosporin antibiotic active against a wide range of gram negative and positive bacteria.
Amoxicillin Clavulanate is a combination of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor.
OTHERIntravenous fluid
Maintenance fluids administered for at least 24 hours.
OTHERNasogastric feeds
Feeds given via nasogastric tube. Feeds may include cow's milk, breast milk, porridge, formula among others.
DRUGAmpicillin
Ampicillin is a penicillin-type antibiotic.
Sponsors
University of Nairobi
London School of Hygiene and Tropical Medicine
National Institute for Health Research, United Kingdom
Department for International Development, United Kingdom
Medical Research Council
Wellcome Trust
Kenya Ministry of Health
University of Oxford
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Months to 59 Months
Healthy volunteers
No
Inclusion criteria
* Age 2 to 59 months. * History of cough or difficulty breathing and signs of severe pneumonia based on WHO 2013 criteria * Admitted to any one of the study hospitals. * Informed consent provided by the parents/guardian.
Exclusion criteria
* Children presenting in cardiorespiratory arrest requiring emergency basic life support (bag-valve-mask ventilation and/or chest compressions). * Children for whom concurrent condition precludes the use of the first-line antibiotics for severe pneumonia such as readmission or meningitis * Known allergy or contraindication to penicillin, gentamicin, ceftriaxone or amoxicillin-clavulanic acid. * Referral from another inpatient facility following treatment with injectable antibiotics for more than 24 hours or because the first-line regimen is considered to have failed * Previously enrolled in the study. * For supportive care intervention (Intravenous fluids versus nasogastric feeds): children with absent gag reflex. * For supportive care intervention (Intravenous fluids versus nasogastric feeds): children unable to maintain oxygen saturations greater 90% on pulse oximetry while receiving supplemental oxygen. * For supportive care intervention (Intravenous fluids versus nasogastric feeds): children with severe acute malnutrition * For supportive care intervention (Intravenous fluids versus nasogastric feeds): shock or severe dehydration * For supportive care intervention (Intravenous fluids versus nasogastric feeds): Child able to feed * For supportive care intervention (Intravenous fluids versus nasogastric feeds): Vomiting everything
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | Up to Day 5 | Mortality of participants receiving any of the injectable antibiotic treatments who die within the first five days of admission measured from source documents, medical records, verbal autopsy or death certificates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of serious adverse events | Up to Day 30 | Serious adverse events that my be likely or definitely related to any of the interventions given to the participants. Serious adverse events include death, a life threatening event, persistent or significant disability or incapacity, hospitalisation or prolonged hospitalisation. |
| Length of hospitalisation | Through duration of hospitalisation, an average of 5 days | Total days a participant is admitted or receives inpatient care measured in days using hospital records at the start and end of each admission. |
| Duration taken to tolerate full fluids by mouth | An average of 3 days | Number of days it takes for participants to fully tolerate fluids orally. |
| Mortality 30 days after enrollment | Day 30 post enrollment | Number of participants who die within 30 days of enrollment into the study measured using source documents, medical records, verbal autopsy or death certificates. |
Countries
Kenya
Outcome results
None listed