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

Pneumonia Clinical Trial

— SEARCH  

Official title:

Supportive Care and Antibiotics for Severe Pneumonia Among Hospitalized Children (SEARCH): A Pragmatic Randomised Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04041791
• Other study ID #: KEMRI/CGMR-C/141/3772
• Status: Completed
• Phase: Phase 3
• Start date: August 19, 2019
• Est. completion date: April 5, 2024

Study information

• Verified date: May 2024
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4392
• Est. completion date: April 5, 2024
• Est. primary completion date: April 5, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months to 59 Months

Eligibility

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 due to dehydration 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

Related Conditions & MeSH terms

• Pneumonia

Intervention

Drug:
• Benzyl penicillin
Benzyl penicillin is a penicillin antibiotic.
• Gentamicin Sulfate
Gentamicin is an aminoglycoside antibiotic.
• Ceftriaxone
Ceftriaxone is a third generation cephalosporin antibiotic active against a wide range of gram negative and positive bacteria.
• Amoxicillin Clavulanate
Amoxicillin Clavulanate is a combination of amoxicillin, a ß-lactam antibiotic, and potassium clavulanate, a ß-lactamase inhibitor.

Other:
• Intravenous fluid
Maintenance fluids administered for at least 24 hours.
• Nasogastric feeds
Feeds given via nasogastric tube. Feeds may include cow's milk, breast milk, porridge, formula among others.

Drug:
• Ampicillin
Ampicillin is a penicillin-type antibiotic.

Locations

Country	Name	City	State
Kenya	Machakos Level 5 Hospital	Machakos

Sponsors (8)

Lead Sponsor	Collaborator
University of Oxford	Department for International Development, United Kingdom, Kenya Ministry of Health, London School of Hygiene and Tropical Medicine, Medical Research Council, National Institute for Health Research, United Kingdom, University of Nairobi, Wellcome Trust

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to Day 5
Secondary	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.	Up to Day 30
Secondary	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.	Through duration of hospitalisation, an average of 5 days
Secondary	Duration taken to tolerate full fluids by mouth	Number of days it takes for participants to fully tolerate fluids orally.	An average of 3 days
Secondary	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.	Day 30 post enrollment