A Study to Compare Different Antibiotics and Different Modes of Fluid Treatment for Children With Severe Pneumonia

University of Oxford4,392 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Interventions

Benzyl penicillinDRUG

Benzyl penicillin is a penicillin antibiotic.

Gentamicin SulfateDRUG

Gentamicin is an aminoglycoside antibiotic.

CeftriaxoneDRUG

Ceftriaxone is a third generation cephalosporin antibiotic active against a wide range of gram negative and positive bacteria.

Amoxicillin ClavulanateDRUG

Amoxicillin Clavulanate is a combination of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor.

Intravenous fluidOTHER

Maintenance fluids administered for at least 24 hours.

Nasogastric feedsOTHER

Feeds given via nasogastric tube. Feeds may include cow's milk, breast milk, porridge, formula among others.

AmpicillinDRUG

Ampicillin is a penicillin-type antibiotic.

Eligibility

Sex: ALLMin age: 2 MonthsMax age: 59 Months

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Mortality

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.

Time frame: Up to Day 5

Secondary Outcomes

Number of serious adverse events

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.

Time frame: Up to Day 30

Length of hospitalisation

Total days a participant is admitted or receives inpatient care measured in days using hospital records at the start and end of each admission.

Time frame: Through duration of hospitalisation, an average of 5 days

Duration taken to tolerate full fluids by mouth

Number of days it takes for participants to fully tolerate fluids orally.

Time frame: An average of 3 days

Mortality 30 days after 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.

Time frame: Day 30 post enrollment