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| Name | Class |
|---|---|
| University of Nairobi | OTHER |
| London School of Hygiene and Tropical Medicine | OTHER |
| National Institute for Health Research, United Kingdom | OTHER_GOV |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Benzyl penicillin | Drug | Benzyl penicillin is a penicillin antibiotic. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ambrose Agweyu, PhD | KEMRI-Wellcome Trust Research Programme, University of Oxford | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Machakos Level 5 Hospital | Machakos | Kenya |
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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| Department for International Development, United Kingdom |
| OTHER_GOV |
| Medical Research Council | OTHER_GOV |
| Wellcome Trust | OTHER |
| Kenya Ministry of Health | OTHER_GOV |
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| 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. |
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| 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. |
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| Gentamicin Sulfate | Drug | Gentamicin is an aminoglycoside antibiotic. |
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| Ceftriaxone | Drug | Ceftriaxone is a third generation cephalosporin antibiotic active against a wide range of gram negative and positive bacteria. |
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| Amoxicillin Clavulanate | Drug | Amoxicillin Clavulanate is a combination of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor. |
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| Intravenous fluid | Other | Maintenance fluids administered for at least 24 hours. |
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| Nasogastric feeds | Other | Feeds given via nasogastric tube. Feeds may include cow's milk, breast milk, porridge, formula among others. |
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| Ampicillin | Drug | Ampicillin is a penicillin-type antibiotic. |
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| 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 |
| 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 |
| 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 |
| ID | Term |
|---|---|
| D011014 | Pneumonia |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D010400 | Penicillin G |
| D005839 | Gentamicins |
| D002443 | Ceftriaxone |
| D019980 | Amoxicillin-Potassium Clavulanate Combination |
| D000077325 | Ringer's Lactate |
| D005947 | Glucose |
| D000077330 | Saline Solution |
| D000667 | Ampicillin |
| ID | Term |
|---|---|
| D010406 | Penicillins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D002439 | Cefotaxime |
| D002505 | Cephacetrile |
| D002511 | Cephalosporins |
| D013843 | Thiazines |
| D019818 | Clavulanic Acid |
| D002969 | Clavulanic Acids |
| D000658 | Amoxicillin |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D006601 | Hexoses |
| D009005 | Monosaccharides |
| D000073893 | Sugars |
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