Using procalcitonin to guide duration of antibiotics
| ISRCTN | ISRCTN11369832 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11369832 |
| Secondary identifying numbers | UoL001333 |
- Submission date
- 06/09/2017
- Registration date
- 20/09/2017
- Last edited
- 14/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Sepsis is defined as the body’s response to infection, which can often be indistinguishable from the response to other insults like burns or surgery. On one hand, giving antibiotics promptly saves lives, but on the other hand, giving antibiotics to people who do not need them leads to overuse of antibiotics and antimicrobial resistance. The Department of Health recommends that antibiotics should be given for as short a course as is safe, to prevent antimicrobial resistance. Most hospitals in the NHS use a blood test called C-Reactive Protein (CRP) to monitor response to infection, but it is not specific for bacterial infection and shows a delayed response to infection. Procalcitonin (PCT) is a blood test which is specific for bacterial infection and responds more quickly than CRP, but is not routinely used in the NHS. Studies done mainly in adults shows that using procalcitonin to guide clinicians may reduce the amount of antibiotics used, reduce hospital stay, and is not associated with adverse effects such as hospital re-admission, incomplete treatment of infections, relapse or death. A recent guideline from the National Institute for Health and Care Excellence (NICE) recommends further research on procalcitonin testing to guide antibiotic use in children. The aim of this study is to compare the current management of severe bacterial infection (SBI) in children (doctors use clinical judgement and may also use CRP to decide on duration of intravenous antibiotics) with procalcitonin-guided management, where the management is identical to current practice, except that doctors have an additional procalcitonin test with advice on how to interpret the result.
Who can participate?
Children up to the age of 18 who are admitted to the hospital for confirmed or suspected bacterial infection.
What does the study involve?
Children hospitalised with suspected or confirmed bacterial infection are randomised to the intervention or control arm. In those randomised to the intervention arm, a Procalcitonin (PCT) test is performed in the hospital laboratory at baseline, days 3-5, days 6-14 and day 28 (if still on IV antibiotics). The PCT results feed into an algorithm that guides antimicrobial prescribing decisions. Children in the control arm do not have the PCT test performed and receive care as usual. Participants are followed up at day 28 with a telephone call or electronic follow up to ask about the quality of life of the children and healthcare utilisation.
What are the possible benefits and risks of participating?
The benefit of taking part is that the information collected will help children/young people in the future. Taking part in the trial will mean giving up some time during the child's hospital stay and at the follow-up telephone call.
Where is the study run from?
This study is being run by the University of Liverpool (UK) and takes place in children’s hospitals in the UK.
When is the study starting and how long is it expected to run for?
September 2017 to January 2023
Who is funding the study?
NIHR HTA Programme
Who is the main contact?
Dr Cherry-Ann Waldron
Contact information
Public
Centre for Trials Research
College of Biomedical & Life Sciences
Cardiff University
7th Floor
Neuadd Meirionnydd
Heath Park
Cardiff
CF14 4YS
United Kingdom
 ORCID ID |
0000-0001-8465-2492 |
|---|---|
| Phone | +44 2929 687609 |
| waldronc@cardiff.ac.uk |
Scientific
University of Liverpool Institute of Infection and Global Health
Ronald Ross Building
8 West Derby Street
Liverpool
L69 7BE
United Kingdom
| Phone | +44 151 794 9535 |
|---|---|
| edcarrol@liverpool.ac.uk |
Study information
| Study design | Prospective two-armed individually randomized controlled trial (RCT) |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection |
| Study acronym | BATCH |
| Study hypothesis | The aim of this study is to determine if the addition of Procalcitonin (PCT) testing to current best practice based on the NICE Antimicrobial Stewardship (AMS) guidelines can safely allow a reduction in duration of antibiotic therapy in hospitalised children with suspected or confirmed bacterial infection compared to current best practice alone. |
| Ethics approval(s) | North West-Liverpool East REC, 13/04/2018, ref: 18/NW/0100 |
| Condition | Bacterial infection |
| Intervention | Children hospitalised with suspected or confirmed bacterial infection are randomised to the intervention or control arm. In those randomised to the intervention arm, a Procalcitonin (PCT) test is performed in the hospital laboratory at baseline, days 3-5, days 6-14 and day 28 (if still on IV antibiotics). The PCT results feed into an algorithm that guides antimicrobial prescribing decisions. Children in the control arm do not have the PCT test performed and receive care as usual. At Day 28, participants receive a telephone or electronic follow up with the parent to ask about the healthcare utilisation and quality of life of the child. |
| Intervention type | Other |
| Primary outcome measure | 1. Antibiotics use is measured using the number of days IV antibiotics are used 2. Safety is measured as the number of patients experiencing one of: 2.1. Unscheduled admissions/re-admissions (to include readmission rate within 7 days of discharge with infective diagnosis, unscheduled readmission to PICU with infective diagnosis, or admission to PICU with infective diagnosis) 2.2. Re-treatment for same condition within 7 days of stopping IV antibiotics (re-starting IV antibiotics which have been stopped), 2.3. Mortality |
| Secondary outcome measures | 1. Total duration of antibiotics (IV and oral) 2. Unscheduled admissions/re-admissions (to include readmission rate within 7 days of discharge with infective diagnosis, unscheduled readmission to PICU with infective diagnosis, or admission to PICU with infective diagnosis.) 3. Re-treatment for same condition within 7 days of stopping IV antibiotics (re-starting IV antibiotics which have been stopped) 4. Time to switch from broad spectrum to narrow spectrum antibiotics 5. Time to discharge from hospital 6. Suspected Adverse Drug Reactions (ADR) is measured using the Liverpool Causality Assessment Tool. 7. Cost of hospital episode is measured using cost analysis. 8. Hospital Acquired Infection (HAI) is measured using up to Day 28 9. Health utility is measured using CHU9D (for children aged 5 and above) up to Day 28. 10 Mortality. Outcome data is recorded daily by the research nurse for all recruited participants (up to and including Day 28, or until discharge). Research nurses review observation and medication charts, medical notes for all recruited participants. |
| Overall study start date | 01/09/2017 |
| Overall study end date | 23/01/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 3 Days |
| Upper age limit | 18 Years |
| Sex | Both |
| Target number of participants | 1942 |
| Total final enrolment | 1951 |
| Participant inclusion criteria | Current inclusion criteria as of 07/11/2019: 1. All children aged between 72 hours old and up to 18 years old admitted to hospital for confirmed or suspected SBI, in whom IV antibiotics are commenced, and expected to remain on IV antibiotics for more than 48 hours 2. Conditions include (but not limited to): bacteraemia, central line-associated bloodstream infections (CLABSIs), uncomplicated bone and joint infections (such as single site infection, osteomyelitis with adjacent septic arthritis or septic arthritis with adjacent osteomyelitis), discitis, empyema, pneumonia, pyelonephritis, sinusitis, retropharyngeal abscess, pyomyositis, uncomplicated culture-negative meningitis, intra-abdominal infections, lymphadenitis, cellulitis 3. First time in the BATCH trial Previous inclusion criteria from 02/05/2018 to 07/11/2019: 1. All children up to 18 years old admitted to hospital for confirmed or suspected bacterial infection or sepsis, in whom IV antibiotics are commenced, and expected to remain on IV antibiotics for at least 48 hours 2. Conditions include: bacteraemia, bone and joint infections, discitis, empyema, pneumonia, pyelonephritis, sinusitis, retropharyngeal abscess, pyomyositis, uncomplicated culture-negative meningitis, intra-abdominal infections, lymphadenitis, cellulitis, central line-associated bloodstream infections (CLABSIs) and bacterial endocarditis 3. First time in the BATCH trial Original inclusion criteria: 1. All children up to 18 years old admitted to hospital for confirmed or suspected bacterial infection or sepsis, in whom IV antibiotics are commenced, and expected to remain on IV antibiotics for at least 48 hours 2. Conditions include: bacteraemia, bone and joint infections, discitis, empyema, pneumonia, pyelonephritis, sinusitis, retropharyngeal abscess, pyomyositis, uncomplicated culture-negative meningitis, intra-abdominal infections, lymphadenitis, cellulitis, bacterial endocarditis |
| Participant exclusion criteria | Current exclusion criteria as of 07/11/2019: 1. Preterm infant age 2. Children admitted moribund and not expected to survive more than 24 hours 3. Children with a predicted duration of intravenous (IV) antibiotics of less than 48 hours 4. Children not expected to survive at least 28 days because of a pre-existing condition 5. Children with bacterial meningitis, bacterial endocarditis, or brain abscess 6. Children with complicated bone and joint infections 7. Children receiving antibiotics for surgical prophylaxis 8. Children with chronic co-morbidities, such as cystic fibrosis, chronic lung disease, bronchiectasis where there is already a pre-defined length of course of antibiotics 9. Children who are severely immunocompromised (e.g. chemotherapy, stem cell transplant, biological therapy for inflammatory or rheumatological conditions) 10. Children who in the opinion of the local investigator, are unsuitable for randomisation due to high probability of requiring sustained IV therapy 11. Children with a presence of existing directive to withhold life-sustaining treatment 12. Added 01/02/2021: Inborn infants admitted to Neonatal Intensive Care Units (NICU), Neonatal High Dependency Units (NHDU), Special Care Baby Units (SCBU) or Postnatal wards Previous exclusion criteria: 1. Preterm infant age <37 weeks corrected gestational age or ≥18 years of age 2. Children admitted moribund and not expected to survive more than 24 hours 3. Children with a predicted duration of stay of less than 48 hours 4. Children not expected to survive at least 28 days because of a pre-existing condition 5. Bacterial meningitis, bacterial endocarditis, brain abscess 6. Children receiving antibiotics for surgical prophylaxis 7. Chronic co-morbidities, such as cystic fibrosis, chronic lung disease, bronchiectasis 8. Severe immunocompromised (e.g. chemotherapy, stem cell transplant, biological therapy for inflammatory or rheumatological conditions, TPN dependent) 9. Presence of existing directive to withhold life-sustaining treatment 10. Added 02/05/2018: Children, who in the opinion of the local investigator, are unsuitable for randomisation due to high probability of requiring long term IV therapy |
| Recruitment start date | 11/06/2018 |
| Recruitment end date | 30/11/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
- Wales
Study participating centres
Liverpool
L12 2AP
United Kingdom
Cardiff
CF14 4XW
United Kingdom
Bristol
BS2 8BJ
United Kingdom
Southampton
SO16 6YD
United Kingdom
Sheffield
S10 2TH
United Kingdom
Crumpsall
M8 5RB
United Kingdom
Oxford
OX3 9DU
United Kingdom
London
SE13 6LH
United Kingdom
Exeter
EX2 5DW
United Kingdom
Poole
BH15 2JB
United Kingdom
Chester
CH2 1UL
United Kingdom
Uttoxeter Road
Derby
DE22 3NE
United Kingdom
Cosham
Portsmouth
PO6 3LY
United Kingdom
Sponsor information
University/education
Research Support Office
2nd Floor Block D
Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
England
United Kingdom
"ROR" |
https://ror.org/04xs57h96 |
|---|
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 28/02/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The trialists intend to publish the main trial results in international peer-reviewed journals and present at national and international scientific meetings. A protocol paper will be submitted for publication. Additional documentation will be available upon request. |
| IPD sharing plan | The datasets generated during the current study are available upon request from the Centre for Trials Research, Cardiff University by contacting the trial manager at BATCH@cardiff.ac.uk. Pseudo-anonymised data will be provided upon production of the requestor’s study protocol and agreement by Centre of Trials Research and study sponsor (University of Liverpool). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 25/01/2022 | 27/01/2022 | Yes | No | |
| Statistical Analysis Plan | SAP article | 30/05/2023 | 31/05/2023 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 08/01/2025 | 14/01/2025 | Yes | No |
Editorial Notes
14/01/2025: Publication reference added.
16/12/2024: The intention to publish date was changed from 31/12/2024 to 28/02/2025.
12/09/2024: The intention to publish date was changed from 30/09/2024 to 31/12/2024.
21/06/2024: The intention to publish date was changed from 30/06/2024 to 30/09/2024.
15/03/2024: The intention to publish date was changed from 31/03/2024 to 30/06/2024.
17/01/2024: The intention to publish date was changed from 31/01/2024 to 31/03/2024.
10/07/2023: The intention to publish date was changed from 30/09/2023 to 31/01/2024.
31/05/2023: Publication reference added.
07/02/2023: The participant level data sharing statement was updated.
30/01/2023: The following changes were made to the trial record:
1. The overall end date was changed from 31/12/2022 to 23/01/2023.
2. the total final enrolment was added.
29/09/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2021 to 30/11/2022.
2. The overall end date was changed from 30/09/2022 to 31/12/2022.
3. The intention to publish date was changed from 30/07/2023 to 30/09/2023.
4. The plain English summary was updated to reflect these changes.
27/01/2022: Publication reference added.
30/12/2021: The following changes have been made:
1. The overall trial end date has been changed from 28/02/2022 to 30/09/2022 and the plain English summary updated accordingly.
2. The intention to publish date has been changed from 01/09/2022 to 30/07/2023.
17/02/2021: Royal Derby Hospital and Queen Alexandra Hospital were added as trial participating centres.
01/02/2021: The recruitment end date was changed from 31/03/2021 to 31/12/2021. The exclusion criteria were updated.
13/07/2020: The trial contact details have been made publicly visible.
25/06/2020: Recruitment has resumed.
24/04/2020: Due to current public health guidance, recruitment for this study has been paused.
07/11/2019: The following changes were made to the trial record:
1. The recruitment start date was changed from 11/04/2018 to 11/06/2018.
2. The recruitment end date was changed from 31/03/2020 to 31/03/2021.
3. The overall trial end date was changed from 31/08/2020 to 28/02/2022.
4. The intention to publish date was changed from 01/09/2021 to 01/09/2022.
5. The trial participating centres were updated to add Children’s Hospital, John Radcliffe Hospital; University Hospital Lewisham; Royal Devon and Exeter Hospital; Poole Hospital; and Countess of Chester Hospital; and remove Royal Hospital for Children, Glasgow; The Royal Hospital for Sick Children Edinburgh; and Royal Manchester Children’s Hospital.
6. The inclusion and exclusion criteria were updated.
02/05/2018: The following changes were made:
1. Recruitment start date was changed from 01/01/2018 to 11/04/2018.
2. Recruitment end date was changed from 31/12/2019 to 31/03/2020
3. Participant inclusion and exclusion criteria were updated.
4. Ethics approval information was added.
