NCT04041791

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
4,392

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Aug 2019

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 29, 2019

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 1, 2019

Completed
18 days until next milestone

Study Start

First participant enrolled

August 19, 2019

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 5, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 5, 2024

Completed
Last Updated

July 8, 2024

Status Verified

July 1, 2024

Enrollment Period

4.6 years

First QC Date

July 29, 2019

Last Update Submit

July 4, 2024

Conditions

Keywords

severe pneumoniasupportive careantibioticsWorld Health Organisationintravenous fluidsnutritionchildren

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • Number of serious adverse events

    Up to Day 30

  • Length of hospitalisation

    Through duration of hospitalisation, an average of 5 days

  • Duration taken to tolerate full fluids by mouth

    An average of 3 days

  • Mortality 30 days after enrollment

    Day 30 post enrollment

Study Arms (6)

Benzyl penicillin/ampicillin + gentamicin & IV fluids

ACTIVE COMPARATOR

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.

Drug: Benzyl penicillinDrug: Gentamicin SulfateOther: Intravenous fluidDrug: Ampicillin

Ceftriaxone and IV fluids

EXPERIMENTAL

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.

Drug: CeftriaxoneOther: Intravenous fluid

Amoxicillin-clavulanate and IV fluids

EXPERIMENTAL

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.

Drug: Amoxicillin ClavulanateOther: Intravenous fluid

Benzyl penicillin/ampicillin + gentamicin & NG feeds

EXPERIMENTAL

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.

Drug: Benzyl penicillinDrug: Gentamicin SulfateOther: Nasogastric feedsDrug: Ampicillin

Ceftriaxone and NG feeds

EXPERIMENTAL

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.

Drug: CeftriaxoneOther: Nasogastric feeds

Amoxicillin-clavulanic acid and NG feeds

EXPERIMENTAL

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.

Drug: Amoxicillin ClavulanateOther: Nasogastric feeds

Interventions

Benzyl penicillin is a penicillin antibiotic.

Also known as: Medipen, Cristapen
Benzyl penicillin/ampicillin + gentamicin & IV fluidsBenzyl penicillin/ampicillin + gentamicin & NG feeds

Gentamicin is an aminoglycoside antibiotic.

Also known as: Gentamicin, Gentamed
Benzyl penicillin/ampicillin + gentamicin & IV fluidsBenzyl penicillin/ampicillin + gentamicin & NG feeds

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

Also known as: Desefin
Ceftriaxone and IV fluidsCeftriaxone and NG feeds

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

Also known as: Amoxicillin-clavulanic acid, Amoxi-clav, Amoklavin, Co-amoxiclav
Amoxicillin-clavulanate and IV fluidsAmoxicillin-clavulanic acid and NG feeds

Maintenance fluids administered for at least 24 hours.

Also known as: Hartmann's Solution with 5% dextrose, Ringer's Lactate with 5% dextrose, Normal Saline with 5% dextrose
Amoxicillin-clavulanate and IV fluidsBenzyl penicillin/ampicillin + gentamicin & IV fluidsCeftriaxone and IV fluids

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

Amoxicillin-clavulanic acid and NG feedsBenzyl penicillin/ampicillin + gentamicin & NG feedsCeftriaxone and NG feeds

Ampicillin is a penicillin-type antibiotic.

Benzyl penicillin/ampicillin + gentamicin & IV fluidsBenzyl penicillin/ampicillin + gentamicin & NG feeds

Eligibility Criteria

Age2 Months - 59 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Machakos Level 5 Hospital

Machakos, Kenya

Location

MeSH Terms

Conditions

Pneumonia

Interventions

Penicillin GGentamicinsCeftriaxoneAmoxicillin-Potassium Clavulanate CombinationRinger's LactateGlucoseSaline SolutionAmpicillin

Condition Hierarchy (Ancestors)

Respiratory Tract InfectionsInfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Penicillinsbeta-LactamsLactamsAmidesOrganic ChemicalsSulfur CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsAminoglycosidesGlycosidesCarbohydratesCefotaximeCephacetrileCephalosporinsThiazinesClavulanic AcidClavulanic AcidsAmoxicillinDrug CombinationsPharmaceutical PreparationsCrystalloid SolutionsIsotonic SolutionsSolutionsHexosesMonosaccharidesSugars

Study Officials

  • Ambrose Agweyu, PhD

    KEMRI-Wellcome Trust Research Programme, University of Oxford

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

July 29, 2019

First Posted

August 1, 2019

Study Start

August 19, 2019

Primary Completion

April 5, 2024

Study Completion

April 5, 2024

Last Updated

July 8, 2024

Record last verified: 2024-07

Data Sharing

IPD Sharing
Will not share

Data requests will be considered by applying to the Data Governance Committee at the Kenya Medical Research Institute (KEMRI) Centre for Geographic Medicine Research-Kilifi, Kenya who will manage the process and ensure that appropriate ethical approval is in place and consent has been obtained for dissemination and use outside of the scope of the trial.

Locations