PneumoniaPhase 3SEARCHNCT04041791
A Study to Compare Different Antibiotics and Different Modes of Fluid Treatment for Children With Severe Pneumonia
A Phase 3 study testing Benzyl penicillin, Gentamicin Sulfate and Ceftriaxone in people with Pneumonia, run by University of Oxford at 1 site in Kenya.
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. Read more about this study
- Who is it for?
- Ages 2 to 59 months
- Conditions the study is for
- Pneumonia
- What is being tested?
- Benzyl penicillin, Gentamicin Sulfate and Ceftriaxone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4,392 participants
- Where
- 1 siteKenya
- Study dates
- 19 Aug 2019to 5 Apr 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 59 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Supportive Care and Antibiotics for Severe Pneumonia Among Hospitalized Children (SEARCH): A Pragmatic Randomised Controlled Trial
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.
Read the 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.
- Conditions
- Pneumonia
- Being tested
- Benzyl penicillin, Gentamicin Sulfate, Ceftriaxone, Amoxicillin Clavulanate, Intravenous fluid
- Keywords
- severe pneumonia, supportive care, antibiotics, World Health Organisation, intravenous fluids, nutrition, children
- Medical subject headings
- Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Benzyl penicillinDrug
Also called Medipen, Cristapen
Benzyl penicillin is a penicillin antibiotic.
Gentamicin SulfateDrug
Also called Gentamicin, Gentamed
Gentamicin is an aminoglycoside antibiotic.
CeftriaxoneDrug
Also called Desefin
Ceftriaxone is a third generation cephalosporin antibiotic active against a wide range of gram negative and positive bacteria.
Amoxicillin ClavulanateDrug
Also called Amoxicillin-clavulanic acid, Amoxi-clav, Amoklavin, Co-amoxiclav
Amoxicillin Clavulanate is a combination of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor.
Intravenous fluidOther
Also called Hartmann's Solution with 5% dextrose, Ringer's Lactate with 5% dextrose, Normal Saline with 5% dextrose
Maintenance fluids administered for at least 24 hours.
Nasogastric feedsOther
Feeds given via nasogastric tube. Feeds may include cow's milk, breast milk, porridge, formula among others.
AmpicillinDrug
Ampicillin is a penicillin-type antibiotic.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Benzyl penicillin; Drug: Gentamicin Sulfate; Other: Intravenous fluid; Drug: 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. Receives: Drug: Ceftriaxone; Other: 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. Receives: Drug: Amoxicillin Clavulanate; Other: 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. Receives: Drug: Benzyl penicillin; Drug: Gentamicin Sulfate; Other: Nasogastric feeds; Drug: 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. Receives: Drug: Ceftriaxone; Other: 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. Receives: Drug: Amoxicillin Clavulanate; Other: Nasogastric feeds |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to Day 5
Secondary outcomes (4)
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.
Measured: Up to Day 30
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.
Measured: Through duration of hospitalisation, an average of 5 days
Duration taken to tolerate full fluids by mouth
Number of days it takes for participants to fully tolerate fluids orally.
Measured: An average of 3 days
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.
Measured: Day 30 post enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2019
- Study start19 Aug 2019
- Primary completion5 Apr 2024
- Study completion5 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PneumoniaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 4,392 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Principal investigator, Ambrose Agweyu, University of Oxford
- Investigators
- Ambrose Agweyu, PhD, Principal investigator, KEMRI-Wellcome Trust Research Programme, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04041791
- Sponsor's protocol ID
- KEMRI/CGMR-C/141/3772
- Acronym
- SEARCH
- Status last verified
- Jul 2024
- First submitted
- 29 Jul 2019
- Last updated
- 8 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Supportive Care and Antibiotics for Severe Pneumonia Among Hospitalized Children (SEARCH): A Pragmatic Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT04041791
- Acronym / sponsor ID
- SEARCH / KEMRI/CGMR-C/141/3772
- Conditions
- Pneumonia
- Keywords
- severe pneumonia, supportive care, antibiotics, World Health Organisation, intravenous fluids, nutrition, children
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4,392 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- 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
- Study start
- 19 Aug 2019 (actual)
- Primary completion
- 5 Apr 2024 (actual)
- Study completion
- 5 Apr 2024 (actual)
- First posted
- 1 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Benzyl penicillin/ampicillin + gentamicin & IV fluids | Active comparator | Drug: Benzyl penicillin, Drug: Gentamicin Sulfate, Other: Intravenous fluid, Drug: AmpicillinParticipants 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. |
| Ceftriaxone and IV fluids | Experimental | Drug: Ceftriaxone, Other: Intravenous fluidParticipants 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. |
| Amoxicillin-clavulanate and IV fluids | Experimental | Drug: Amoxicillin Clavulanate, Other: Intravenous fluidParticipants 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. |
| Benzyl penicillin/ampicillin + gentamicin & NG feeds | Experimental | Drug: Benzyl penicillin, Drug: Gentamicin Sulfate, Other: Nasogastric feeds, Drug: AmpicillinParticipants 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. |
| Ceftriaxone and NG feeds | Experimental | Drug: Ceftriaxone, Other: Nasogastric feedsParticipants 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. |
| Amoxicillin-clavulanic acid and NG feeds | Experimental | Drug: Amoxicillin Clavulanate, Other: Nasogastric feedsParticipants 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. |
Who may qualify
- Ages
- 2 to 59 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Benzyl penicillinAlso: Medipen, CristapenBenzyl penicillin is a penicillin antibiotic. | Drug | Benzyl penicillin/ampicillin + gentamicin & IV fluids, Benzyl penicillin/ampicillin + gentamicin & NG feeds |
| Gentamicin SulfateAlso: Gentamicin, GentamedGentamicin is an aminoglycoside antibiotic. | Drug | Benzyl penicillin/ampicillin + gentamicin & IV fluids, Benzyl penicillin/ampicillin + gentamicin & NG feeds |
| CeftriaxoneAlso: DesefinCeftriaxone is a third generation cephalosporin antibiotic active against a wide range of gram negative and positive bacteria. | Drug | Ceftriaxone and IV fluids, Ceftriaxone and NG feeds |
| Amoxicillin ClavulanateAlso: Amoxicillin-clavulanic acid, Amoxi-clav, Amoklavin, Co-amoxiclavAmoxicillin Clavulanate is a combination of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor. | Drug | Amoxicillin-clavulanate and IV fluids, Amoxicillin-clavulanic acid and NG feeds |
| Intravenous fluidAlso: Hartmann's Solution with 5% dextrose, Ringer's Lactate with 5% dextrose, Normal Saline with 5% dextroseMaintenance fluids administered for at least 24 hours. | Other | Amoxicillin-clavulanate and IV fluids, Benzyl penicillin/ampicillin + gentamicin & IV fluids, Ceftriaxone and IV fluids |
| Nasogastric feedsFeeds given via nasogastric tube. Feeds may include cow's milk, breast milk, porridge, formula among others. | Other | Amoxicillin-clavulanic acid and NG feeds, Benzyl penicillin/ampicillin + gentamicin & NG feeds, Ceftriaxone and NG feeds |
| AmpicillinAmpicillin is a penicillin-type antibiotic. | Drug | Benzyl penicillin/ampicillin + gentamicin & IV fluids, Benzyl penicillin/ampicillin + gentamicin & NG feeds |
Primary outcome
Mortality
Time frame: Up to Day 5
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.
4 secondary outcomes
Number of serious adverse events
Time frame: Up to Day 30
Length of hospitalisation
Time frame: Through duration of hospitalisation, an average of 5 days
Duration taken to tolerate full fluids by mouth
Time frame: An average of 3 days
Mortality 30 days after enrollment
Time frame: Day 30 post enrollment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2024.
- Individual participant dataSharing planned: No. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ambrose Agweyu, PhD principal investigator
KEMRI-Wellcome Trust Research Programme, University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Benzyl penicillin, Gentamicin Sulfate and Ceftriaxone in people with Pneumonia, run by University of Oxford at 1 site in Kenya.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality (time frame: Up to Day 5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2024.