Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202106720981298 Date of Approval: 23/06/2021
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title A study to compare different injectable antibiotic treatments and different modes of fluid treatment for children with severe pneumonia.
Official scientific title Supportive Care and Antibiotics for Severe Pneumonia among Hospitalised Children (SEARCH): A Pragmatic Randomised Controlled Trial
Brief summary describing the background and objectives of the trial 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.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) SEARCH
Disease(s) or condition(s) being studied Paediatrics
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/07/2019
Actual trial start date 01/08/2019
Anticipated date of last follow up 30/04/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 4392
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Permuted block randomization Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Benzyl penicillin or ampicillin plus Gentamicin and Intravenous 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. Participants will receive antibiotics for a minimum of 48 hours and for up to 7 days. IV Maintenance fluids will be given as a continuous infusion for at least 24 hours. Benzyl penicillin is a penicillin antibiotic Gentamicin is an aminoglycoside antibiotic. Intravenous fluid are maintenance fluids administered for at least 24 hours. The fluids will be Hartmann's Solution with 5% dextrose or Ringer's Lactate with 5% dextrose or Normal Saline with 5% dextrose. Ampicillin is a penicillin-type antibiotic. 1464 Active-Treatment of Control Group
Experimental Group Ceftriaxone and Intravenous IV Fluids Participants are assigned to receive ceftriaxone at 50 mg/kg every 12 hours given intravenously (IV) or via intramuscular (IM) injection Intravenous fluids volumes will be calculated based on the child's weight at admission and will be given as a continuous infusion for at least 24 hours. Ceftriaxone will be given 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. Ceftriaxone is a third generation cephalosporin antibiotic active against a wide range of gram negative and positive bacteria. Intravenous fluid will be maintenance fluids. These include Hartmann's Solution with 5% dextrose or Ringer's Lactate with 5% dextrose or Normal Saline with 5% dextrose 1464
Experimental Group Amoxicillin clavulanic acid and IV fluids Participants are assigned to receive amoxicillin clavulanic acid at 30 mg/kg every 8 hours given intravenously (IV) or via intramuscular (IM). IV fluid volumes will be calculated using the child's weight at admission. Amoxicillin clavulanic acid will be given 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 is a combination of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor. Intravenous fluid will be maintenance fluids. These include Hartmann's Solution with 5% dextrose or Ringer's Lactate with 5% dextrose or Normal Saline with 5% dextrose. 1464
Experimental Group Ceftriaxone and Nasogastric NG feeds Participants are assigned to receive ceftriaxone at 50 mg/kg every 12 hours given intravenously (IV) or via intramuscular (IM) injection. Nasogastric feed volumes will be calculated based on the child's weight and will be given 3 hourly for at least 24 hours. Ceftriaxone will be given for a minimum of 48 hours and for upto 7 days. Nasogastric feeds will be given for at least 24 hours. Ceftriaxone is a third generation cephalosporin antibiotic active against a wide range of gram negative and positive bacteria. Nasogastric Feeds will be given via nasogastric tube. Feeds may include cow's milk, breast milk, porridge, formula or blended foods. 1464
Experimental Group Amoxicillin clavulanic acid and Nasogastric feeds Participants are assigned to receive amoxicillin clavulanic acid at 30 mg/kg every 8 hours given intravenously (IV) or via intramuscular (IM). Nasogastric feed volumes will be calculated based on the child's weight and will be given 3 hourly for at least 24 hours. Amoxicillin clavulanic acid will be given for a minimum of 48 hours and for up to 7 days. Nasogastric feeds will be given for at least 24 hours. Amoxicillin Clavulanate is a combination of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor. Nasogastric Feeds will be given via nasogastric tube. Feeds may include cow's milk, breast milk, porridge, formula or blended foods. 1464
Experimental Group Benzyl penicillin or Ampicillin plus gentamicin and Nasogastric 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. Nasogastric feed volumes will be calculated based on the child's weight and will be given 3 hourly for at least 24 hours. Participants will receive antibiotics for a minimum of 48 hours and for up to 7 days. Nasogastric feeds will be given for at least 24 hours. Benzyl penicillin is a penicillin antibiotic Gentamicin is an aminoglycoside antibiotic. Ampicillin is a penicillin-type antibiotic. Nasogastric Feeds will be given via nasogastric tube. Feeds may include cow's milk, breast milk, porridge, formula or blended foods. 1464
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• 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. • 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 Randomisation 2 (IV fluid versus nasogastric feeds): children with absent gag reflex. • For Randomisation 2 (IV fluid versus nasogastric feeds): children unable to maintain oxygen saturations 90% on pulse oximetry while receiving supplemental oxygen. • For Randomisation 2 (IV fluid versus nasogastric feeds): children with severe acute malnutrition • For Randomisation 2 (IV fluid versus nasogastric feeds): shock or severe dehydration • For Randomisation 2 (IV fluid versus nasogastric feeds): vomiting everything • For Randomisation 2 (IV fluid versus nasogastric feeds): able to feed Infant: 1 Month-23 Month,Preschool Child: 2 Year-5 Year 2 Month(s) 59 Month(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 09/05/2019 Oxford Tropical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Wellington Square, Oxford OX1 2JD London OX12JD United Kingdom
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 14/02/2019 KEMRI Scientific Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
P.O Box 54840 Nairobi 00200 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 08/02/2021 KEMRI Scientific Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
P.O Box 54840 Nairobi 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Mortality Mortality of participants receiving any of the injectable antibiotic treatments who die within the first five days of admission. Day 5 post enrolment or admission.
Primary Outcome Mortality Mortality of participants receiving any of the supportive care treatments who die within the first five days of admission. Day 5 post admission or enrolment
Secondary Outcome Number of serious adverse events defined as serious adverse events that may 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 post admission.
Secondary Outcome Length of hospitalisation defined as the total days a participant is admitted or receives inpatient care measured in days using hospital records at the start and end of each admission Throughout the duration of hospitalisation.
Secondary Outcome Duration taken to tolerate full fluids by mouth defined as the number of days it takes for participants to fully tolerate fluids orally Throughout the duration of admission.
Secondary Outcome Mortality 30 days after enrollment defined as the number of participants who die within 30 days of enrollment into the study. Day 30 post enrolment
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Bungoma County Referral Hospital Bungoma Town Bungoma Kenya
Busia County Hospital Busia Town Busia Kenya
Embu Level 5 Hospital Embu Town Embu Kenya
Kakamega County Teaching and Referral Hospital Kakamega Kakamega Kenya
Kiambu County Referral Hospital Kiambu Kiambu Kenya
Kisumu County Hospital Kisumu Kisumu Kenya
Kitale County Referral Hospital Kitale Kitale Kenya
Mama Lucy Kibaki Hospital Nairobi Nairobi Kenya
Machakos Level 5 Hospital Machakos Town Machakos Kenya
Naivasha County Referral Hospital Naivasha Naivasha Kenya
Thika Level 5 Hospital Thika Town Thika Kenya
Nakuru Level 6 Hospital Nakuru Town Nakuru Kenya
Jaramogi Oginga Odinga Teaching and Referral Hospital Kisumu Kisumu Kenya
Kisii Teaching and Referral Hospital Kisii Town Kisii Kenya
Kerugoya County Referral Hospital Kerugoya Kirinyaga Kenya
Mama Margaret Uhuru Hospital Nairobi Nairobi Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Medical Research Council Wellington Square Oxford Oxford United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Oxford Research Governance Ethics and Assurance Boundary Brook House, Churchill Drive Oxford United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
University of Nairobi Nairobi Nairobi Kenya
London School of Hygiene and Tropical Medicine Keppel St London London United Kingdom
Medical Research Council Oxford Oxford United Kingdom
Ministry of Health Kenya Cathedral Road Nairobi Kenya
Wellcome Trust Euston Road London United Kingdom
Department for International Development United Kingdom London London United Kingdom
National Institute for Health Research United Kingdom London London United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Ambrose Agweyu AAgweyu@kemri-wellcome.org +254722619257 P.O Box 43640
City Postal code Country Position/Affiliation
Nairobi 00100 Kenya KEMRI Wellcome Trust Research Programme
Role Name Email Phone Street address
Public Enquiries Lynda Isaaka LIsaaka@kemri-wellcome.org +254725383089 P.O Box 43640
City Postal code Country Position/Affiliation
Nairobi 00100 Kenya KWTRP
Role Name Email Phone Street address
Scientific Enquiries Ambrose Agweyu AAgweyu@kemri-wellcome.org +254722619257 P.O Box 43640
City Postal code Country Position/Affiliation
Nairobi Kenya KWTRP
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Upon publication of the primary study findings, data requests will be considered by applying to the Data Governance Committee at CGMR-C Kilifi who will manage the process and ensure that appropriate ethical approval is in place and consent has been obtained for uses outside of the study team. Study Protocol Beginning 2 years and ending 5 years after the completion of the trial. Investigators whose proposed use of the data has been approved by an independent review committee.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information