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

NCT ID: NCT04041791

Last Updated: 2024-07-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

4392 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-19

Study Completion Date

2024-04-05

Brief Summary

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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

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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.

Conditions

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Pneumonia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Benzyl penicillin/ampicillin + gentamicin & IV fluids

Participants are assigned to receive benzyl penicillin at 50,000 IU/kg every 6 hours or ampicillin 50mg/kg every 8 hours plus gentamicin 7.5 mg/kg once daily given intravenously (IV) or via intramuscular (IM) injection for a minimum of 48 hours and for up to 7 days.

Maintenance fluids will be given as a continuous infusion for at least 24 hours.

Group Type ACTIVE_COMPARATOR

Intravenous fluid

Intervention Type OTHER

Maintenance fluids administered for at least 24 hours.

Ampicillin

Intervention Type DRUG

Ampicillin is a penicillin-type antibiotic.

Benzyl penicillin

Intervention Type DRUG

Benzyl penicillin is a penicillin antibiotic.

Gentamicin Sulfate

Intervention Type DRUG

Gentamicin is an aminoglycoside antibiotic.

Ceftriaxone and IV fluids

Participants are assigned to receive ceftriaxone at 50 mg/kg every 12 hours given IV or IM for a minimum of 48 hours and for up to 7 days.

Intravenous fluids will be given as a continuous infusion for at least 24 hours.

Group Type EXPERIMENTAL

Ceftriaxone

Intervention Type DRUG

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

Intravenous fluid

Intervention Type OTHER

Maintenance fluids administered for at least 24 hours.

Amoxicillin-clavulanate and IV fluids

Participants are assigned to receive amoxicillin clavulanic acid at 30 mg/kg every 8 hours given IV or IM for a minimum of 48 hours and for up to 7 days.

Intravenous fluids will be given as a continuous infusion for at least 24 hours.

Group Type EXPERIMENTAL

Amoxicillin Clavulanate

Intervention Type DRUG

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

Intravenous fluid

Intervention Type OTHER

Maintenance fluids administered for at least 24 hours.

Benzyl penicillin/ampicillin + gentamicin & NG feeds

Participants are assigned to receive Benzyl penicillin at 50,000 IU/kg every 6 hours or ampicillin 50mg/kg every 8 hours plus gentamicin 7.5 mg/kg once daily given intravenously (IV) or via intramuscular (IM) injection for a minimum of 48 hours and for up to 7 days.

Nasogastric feeds will be given 3 hourly for at least 24 hours.

Group Type EXPERIMENTAL

Nasogastric feeds

Intervention Type OTHER

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

Ampicillin

Intervention Type DRUG

Ampicillin is a penicillin-type antibiotic.

Benzyl penicillin

Intervention Type DRUG

Benzyl penicillin is a penicillin antibiotic.

Gentamicin Sulfate

Intervention Type DRUG

Gentamicin is an aminoglycoside antibiotic.

Ceftriaxone and NG feeds

Participants are assigned to receive ceftriaxone at 50 mg/kg every 12 hours given IV or IM for up to 7 days.

Nasogastric feeds will be given 3 hourly for at least 24 hours.

Group Type EXPERIMENTAL

Ceftriaxone

Intervention Type DRUG

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

Nasogastric feeds

Intervention Type OTHER

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

Amoxicillin-clavulanic acid and NG feeds

Participants are assigned to receive amoxicillin clavulanic acid at 30 mg/kg every 8 hours given IV or IM for up to 7 days.

Nasogastric feeds will be given 3 hourly for at least 24 hours.

Group Type EXPERIMENTAL

Amoxicillin Clavulanate

Intervention Type DRUG

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

Nasogastric feeds

Intervention Type OTHER

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

Interventions

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Ceftriaxone

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

Intervention Type DRUG

Amoxicillin Clavulanate

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

Intervention Type DRUG

Intravenous fluid

Maintenance fluids administered for at least 24 hours.

Intervention Type OTHER

Nasogastric feeds

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

Intervention Type OTHER

Ampicillin

Ampicillin is a penicillin-type antibiotic.

Intervention Type DRUG

Benzyl penicillin

Benzyl penicillin is a penicillin antibiotic.

Intervention Type DRUG

Gentamicin Sulfate

Gentamicin is an aminoglycoside antibiotic.

Intervention Type DRUG

Other Intervention Names

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Medipen Cristapen Gentamicin Gentamed Desefin Amoxicillin-clavulanic acid Amoxi-clav Amoklavin Co-amoxiclav Hartmann's Solution with 5% dextrose Ringer's Lactate with 5% dextrose Normal Saline with 5% dextrose

Eligibility Criteria

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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
Minimum Eligible Age

2 Months

Maximum Eligible Age

59 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Nairobi

OTHER

Sponsor Role collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role collaborator

National Institute for Health Research, United Kingdom

OTHER_GOV

Sponsor Role collaborator

Department for International Development, United Kingdom

OTHER_GOV

Sponsor Role collaborator

Medical Research Council

OTHER_GOV

Sponsor Role collaborator

Wellcome Trust

OTHER

Sponsor Role collaborator

Kenya Ministry of Health

OTHER_GOV

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Ambrose Agweyu

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ambrose Agweyu, PhD

Role: PRINCIPAL_INVESTIGATOR

KEMRI-Wellcome Trust Research Programme, University of Oxford

Locations

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Machakos Level 5 Hospital

Machakos, , Kenya

Site Status

Countries

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Kenya

Other Identifiers

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KEMRI/CGMR-C/141/3772

Identifier Type: -

Identifier Source: org_study_id

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