Back to resultsA Study to Compare Different Antibiotics and Different Modes of Fluid Treatment for Children With Severe Pneumonia (SEARCH)
Primary Purpose
Pneumonia
Status
Recruiting
Phase
Phase 3
Locations
Kenya
Study Type
Interventional
Intervention
Benzyl penicillin
Gentamicin Sulfate
Ceftriaxone
Amoxicillin Clavulanate
Intravenous fluid
Nasogastric feeds
Ampicillin
Sponsored by
About this trial
This is an interventional treatment trial for Pneumonia focused on measuring severe pneumonia, supportive care, antibiotics, World Health Organisation, intravenous fluids, nutrition, children
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
- Shock due to dehydration or severe dehydration (based on WHO definitions (5)) requiring emergency fluid resuscitation
- 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
Sites / Locations
- Machakos Level 5 HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Active Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Benzyl penicillin/ampicillin + gentamicin & IV fluids
Ceftriaxone and IV fluids
Amoxicillin-clavulanate and IV fluids
Benzyl penicillin/ampicillin + gentamicin & NG feeds
Ceftriaxone and NG feeds
Amoxicillin-clavulanic acid and NG feeds
Arm Description
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.
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.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Duration taken to tolerate full fluids by mouth
Number of days it takes for participants to fully tolerate fluids orally.
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.
Full Information
NCT ID
NCT04041791
First Posted
July 29, 2019
Last Updated
November 1, 2022
Sponsor
University of Oxford
Collaborators
University of Nairobi, London School of Hygiene and Tropical Medicine, National Institute for Health Research, United Kingdom, Department for International Development, United Kingdom, Medical Research Council, Wellcome Trust, Kenya Ministry of Health
1. Study Identification
Unique Protocol Identification Number
NCT04041791
Brief Title
A Study to Compare Different Antibiotics and Different Modes of Fluid Treatment for Children With Severe Pneumonia
Acronym
SEARCH
Official Title
Supportive Care and Antibiotics for Severe Pneumonia Among Hospitalized Children
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 19, 2019 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Oxford
Collaborators
University of Nairobi, London School of Hygiene and Tropical Medicine, National Institute for Health Research, United Kingdom, Department for International Development, United Kingdom, Medical Research Council, Wellcome Trust, Kenya Ministry of Health
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumonia
Keywords
severe pneumonia, supportive care, antibiotics, World Health Organisation, intravenous fluids, nutrition, children
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
4392 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Benzyl penicillin/ampicillin + gentamicin & IV fluids
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Ceftriaxone and IV fluids
Arm Type
Experimental
Arm Description
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.
Arm Title
Amoxicillin-clavulanate and IV fluids
Arm Type
Experimental
Arm Description
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.
Arm Title
Benzyl penicillin/ampicillin + gentamicin & NG feeds
Arm Type
Experimental
Arm Description
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.
Arm Title
Ceftriaxone and NG feeds
Arm Type
Experimental
Arm Description
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.
Arm Title
Amoxicillin-clavulanic acid and NG feeds
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Benzyl penicillin
Other Intervention Name(s)
Medipen, Cristapen
Intervention Description
Benzyl penicillin is a penicillin antibiotic.
Intervention Type
Drug
Intervention Name(s)
Gentamicin Sulfate
Other Intervention Name(s)
Gentamicin, Gentamed
Intervention Description
Gentamicin is an aminoglycoside antibiotic.
Intervention Type
Drug
Intervention Name(s)
Ceftriaxone
Other Intervention Name(s)
Desefin
Intervention Description
Ceftriaxone is a third generation cephalosporin antibiotic active against a wide range of gram negative and positive bacteria.
Intervention Type
Drug
Intervention Name(s)
Amoxicillin Clavulanate
Other Intervention Name(s)
Amoxicillin-clavulanic acid, Amoxi-clav, Amoklavin, Co-amoxiclav
Intervention Description
Amoxicillin Clavulanate is a combination of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor.
Intervention Type
Other
Intervention Name(s)
Intravenous fluid
Other Intervention Name(s)
Hartmann's Solution with 5% dextrose, Ringer's Lactate with 5% dextrose, Normal Saline with 5% dextrose
Intervention Description
Maintenance fluids administered for at least 24 hours.
Intervention Type
Other
Intervention Name(s)
Nasogastric feeds
Intervention Description
Feeds given via nasogastric tube. Feeds may include cow's milk, breast milk, porridge, formula among others.
Intervention Type
Drug
Intervention Name(s)
Ampicillin
Intervention Description
Ampicillin is a penicillin-type antibiotic.
Primary Outcome Measure Information:
Title
Mortality
Description
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 Outcome Measure Information:
Title
Number of serious adverse events
Description
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
Title
Length of hospitalisation
Description
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
Title
Duration taken to tolerate full fluids by mouth
Description
Number of days it takes for participants to fully tolerate fluids orally.
Time Frame
An average of 3 days
Title
Mortality 30 days after enrollment
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Months
Maximum Age & Unit of Time
59 Months
Accepts Healthy Volunteers
No
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
Shock due to dehydration or severe dehydration (based on WHO definitions (5)) requiring emergency fluid resuscitation
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ambrose Agweyu, PhD
Phone
+254722619257
Email
AAgweyu@kemri-wellcome.org
First Name & Middle Initial & Last Name or Official Title & Degree
Mike English, MD
Phone
+254722628700
Email
menglish@kemri-wellcome.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ambrose Agweyu, PhD
Organizational Affiliation
KEMRI-Wellcome Trust Research Programme, University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
Machakos Level 5 Hospital
City
Machakos
Country
Kenya
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charles Nzioki, MMed
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
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.
Learn more about this trial
A Study to Compare Different Antibiotics and Different Modes of Fluid Treatment for Children With Severe Pneumonia
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