Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.


Condition or disease Intervention/treatment Phase
Pneumonia Drug: Benzyl penicillin Drug: Gentamicin Sulfate Drug: Ceftriaxone Drug: Amoxicillin Clavulanate Other: Intravenous fluid Other: Nasogastric feeds Drug: Ampicillin Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 4392 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Supportive Care and Antibiotics for Severe Pneumonia Among Hospitalized Children
Actual Study Start Date : August 19, 2019
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : February 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

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

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

Drug: Ampicillin
Ampicillin is a penicillin-type antibiotic.

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.

Drug: Ceftriaxone
Ceftriaxone is a third generation cephalosporin antibiotic active against a wide range of gram negative and positive bacteria.
Other Name: Desefin

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

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.

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

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.

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

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.

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.

Drug: Ceftriaxone
Ceftriaxone is a third generation cephalosporin antibiotic active against a wide range of gram negative and positive bacteria.
Other Name: Desefin

Other: Nasogastric feeds
Feeds given via nasogastric tube. Feeds may include cow's milk, breast milk, porridge, formula among others.

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.

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: Nasogastric feeds
Feeds given via nasogastric tube. Feeds may include cow's milk, breast milk, porridge, formula among others.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Months to 59 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04041791


Locations
Layout table for location information
Kenya
Machakos Level 5 Hospital
Machakos, Kenya
Sponsors and Collaborators
University of Oxford
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
Layout table for investigator information
Principal Investigator: Ambrose Agweyu, PhD KEMRI-Wellcome Trust Research Programme, University of Oxford
Layout table for additonal information
Responsible Party: Ambrose Agweyu, Principal Investigator, University of Oxford
ClinicalTrials.gov Identifier: NCT04041791    
Other Study ID Numbers: KEMRI/CGMR-C/CSC/141/2018
First Posted: August 1, 2019    Key Record Dates
Last Update Posted: November 18, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
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.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ambrose Agweyu, University of Oxford:
severe pneumonia
supportive care
antibiotics
World Health Organisation
intravenous fluids
nutrition
children
Additional relevant MeSH terms:
Layout table for MeSH terms
Pneumonia
Respiratory Tract Infections
Infections
Lung Diseases
Respiratory Tract Diseases
Amoxicillin
Gentamicins
Ceftriaxone
Clavulanic Acid
Clavulanic Acids
Penicillins
Ampicillin
Amoxicillin-Potassium Clavulanate Combination
Penicillin G
Penicillin G Benzathine
Penicillin G Procaine
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
beta-Lactamase Inhibitors