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A Study to Compare Different Antibiotics and Different Modes of Fluid Treatment for Children With Severe Pneumonia (SEARCH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04041791
Recruitment Status : Suspended (Temporarily suspension due to the COVID19 pandemic and will resume once it is deemed safe.)
First Posted : August 1, 2019
Last Update Posted : November 18, 2020
Sponsor:
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
Information provided by (Responsible Party):
Ambrose Agweyu, University of Oxford

Tracking Information
First Submitted Date  ICMJE July 29, 2019
First Posted Date  ICMJE August 1, 2019
Last Update Posted Date November 18, 2020
Actual Study Start Date  ICMJE August 19, 2019
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 31, 2019)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2019)
  • Number of serious adverse events [ Time Frame: Up to Day 30 ]
    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 [ Time Frame: Through duration of hospitalisation, an average of 5 days ]
    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 [ Time Frame: An average of 3 days ]
    Number of days it takes for participants to fully tolerate fluids orally.
  • Mortality 30 days after enrollment [ Time Frame: Day 30 post 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Compare Different Antibiotics and Different Modes of Fluid Treatment for Children With Severe Pneumonia
Official Title  ICMJE Supportive Care and Antibiotics for Severe Pneumonia Among Hospitalized Children
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pneumonia
Intervention  ICMJE
  • Drug: Benzyl penicillin
    Benzyl penicillin is a penicillin antibiotic.
    Other Names:
    • Medipen
    • Cristapen
  • Drug: Gentamicin Sulfate
    Gentamicin is an aminoglycoside antibiotic.
    Other Names:
    • Gentamicin
    • Gentamed
  • Drug: Ceftriaxone
    Ceftriaxone is a third generation cephalosporin antibiotic active against a wide range of gram negative and positive bacteria.
    Other Name: Desefin
  • Drug: Amoxicillin Clavulanate
    Amoxicillin Clavulanate is a combination of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a β-lactamase inhibitor.
    Other Names:
    • Amoxicillin-clavulanic acid
    • Amoxi-clav
    • Amoklavin
    • Co-amoxiclav
  • Other: Intravenous fluid
    Maintenance fluids administered for at least 24 hours.
    Other Names:
    • Hartmann's Solution with 5% dextrose
    • Ringer's Lactate with 5% dextrose
    • Normal Saline with 5% dextrose
  • Other: Nasogastric feeds
    Feeds given via nasogastric tube. Feeds may include cow's milk, breast milk, porridge, formula among others.
  • Drug: Ampicillin
    Ampicillin is a penicillin-type antibiotic.
Study Arms  ICMJE
  • Active Comparator: Benzyl penicillin/ampicillin + gentamicin & IV 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 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.

    Interventions:
    • Drug: Benzyl penicillin
    • Drug: Gentamicin Sulfate
    • Other: Intravenous fluid
    • Drug: Ampicillin
  • Experimental: Ceftriaxone and IV fluids

    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.

    Interventions:
    • Drug: Ceftriaxone
    • Other: Intravenous fluid
  • Experimental: Amoxicillin-clavulanate and IV fluids

    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.

    Interventions:
    • Drug: Amoxicillin Clavulanate
    • Other: Intravenous fluid
  • Experimental: Benzyl penicillin/ampicillin + gentamicin & 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 for a minimum of 48 hours and for up to 7 days.

    Nasogastric feeds will be given 3 hourly for at least 24 hours.

    Interventions:
    • Drug: Benzyl penicillin
    • Drug: Gentamicin Sulfate
    • Other: Nasogastric feeds
    • Drug: Ampicillin
  • Experimental: Ceftriaxone and NG feeds

    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.

    Interventions:
    • Drug: Ceftriaxone
    • Other: Nasogastric feeds
  • Experimental: Amoxicillin-clavulanic acid and NG feeds

    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.

    Interventions:
    • Drug: Amoxicillin Clavulanate
    • Other: Nasogastric feeds
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: July 31, 2019)
4392
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2023
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Months to 59 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Kenya
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04041791
Other Study ID Numbers  ICMJE KEMRI/CGMR-C/CSC/141/2018
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
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.
Current Responsible Party Ambrose Agweyu, University of Oxford
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Oxford
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • 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
Investigators  ICMJE
Principal Investigator: Ambrose Agweyu, PhD KEMRI-Wellcome Trust Research Programme, University of Oxford
PRS Account University of Oxford
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP