A Study to Compare Different Antibiotics and Different Modes of Fluid Treatment for Children With Severe Pneumonia (SEARCH)
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| ClinicalTrials.gov Identifier: NCT04041791 |
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Recruitment Status :
Recruiting
First Posted : August 1, 2019
Last Update Posted : November 2, 2022
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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.
| 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 |
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 : | 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 : | September 2023 |
| Estimated Study Completion Date : | December 2023 |
| Arm | Intervention/treatment |
|---|---|
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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:
Drug: Gentamicin Sulfate Gentamicin is an aminoglycoside antibiotic.
Other Names:
Other: Intravenous fluid Maintenance fluids administered for at least 24 hours.
Other Names:
Drug: Ampicillin Ampicillin is a penicillin-type antibiotic. |
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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:
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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:
Other: Intravenous fluid Maintenance fluids administered for at least 24 hours.
Other Names:
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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:
Drug: Gentamicin Sulfate Gentamicin is an aminoglycoside antibiotic.
Other Names:
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. |
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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. |
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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:
Other: Nasogastric feeds Feeds given via nasogastric tube. Feeds may include cow's milk, breast milk, porridge, formula among others. |
- 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.
- 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.
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| Ages Eligible for Study: | 2 Months to 59 Months (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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
| Contact: Ambrose Agweyu, PhD | +254722619257 | AAgweyu@kemri-wellcome.org | |
| Contact: Mike English, MD | +254722628700 | menglish@kemri-wellcome.org |
| Kenya | |
| Machakos Level 5 Hospital | Recruiting |
| Machakos, Kenya | |
| Contact: Charles Nzioki, MMed | |
| Principal Investigator: | Ambrose Agweyu, PhD | KEMRI-Wellcome Trust Research Programme, University of Oxford |
| 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 2, 2022 |
| Last Verified: | November 2022 |
| 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. |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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severe pneumonia supportive care antibiotics World Health Organisation |
intravenous fluids nutrition children |
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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 |