Clinical trial NCT04041791: A Study to Compare Different Antibiotics and Different Modes of Fluid Treatment for Children With Severe Pneumonia
Official title: Supportive Care and Antibiotics for Severe Pneumonia Among Hospitalized Children (SEARCH): A Pragmatic Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia
Keywords: severe pneumonia
supportive care
antibiotics
World Health Organisation
intravenous fluids
nutrition
children
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: University of Nairobi
name: London School of Hygiene and Tropical Medicine
name: National Institute for Health Research, United Kingdom
name: Department for International Development, United Kingdom
name: Medical Research Council
name: Wellcome Trust
name: Kenya Ministry of Health
First posted: 2019-08-01
Enrollment: 4392
Sex: ALL
Minimum age (years): 2
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mortality
timeFrame: Up to Day 5
Secondary outcomes:
measure: Number of serious adverse events
timeFrame: Up to Day 30
measure: Length of hospitalisation
timeFrame: Through duration of hospitalisation, an average of 5 days
measure: Duration taken to tolerate full fluids by mouth
timeFrame: An average of 3 days
measure: Mortality 30 days after enrollment
timeFrame: Day 30 post enrollment
Other outcomes:
Locations:
city: Machakos
country: Kenya
facility: Machakos Level 5 Hospital
Study officials:
affiliation: KEMRI-Wellcome Trust Research Programme, University of Oxford
name: Ambrose Agweyu, PhD
role: PRINCIPAL_INVESTIGATOR
References: