A trial comparing short course antibiotics and standard course antibiotics for the treatment of sepsis
| ISRCTN | ISRCTN40090372 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN40090372 |
| Integrated Research Application System (IRAS) | 317788 |
| Central Portfolio Management System (CPMS) | 57052 |
| National Institute for Health and Care Research (NIHR) | 134101 |
| Sponsor | Newcastle upon Tyne Hospitals NHS Foundation Trust |
| Funder | NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC) |
- Submission date
- 07/11/2023
- Registration date
- 12/12/2023
- Last edited
- 13/04/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Sepsis is a life-threating condition due to a severe infection. It is a common reason for patients to require “life-support”. Sepsis is a leading cause of death worldwide.
Antibiotics are a major part of the treatment of sepsis, but antibiotics also carry significant risks. The overuse of antibiotics promotes the emergence of “superbugs”, can also be toxic to organs such as the liver and can occasionally be responsible for life-threatening bowel infections.
Striking the right balance of using antibiotics appropriately, while avoiding their potential harm, is a challenge. Antibiotics are initiated rapidly for sepsis because of the severity of illness but once started, the exact duration needed to treat an infection adequately is unknown. Determining a duration of antibiotics that effectively treats sepsis, but is not unnecessarily prolonged, could have a big impact on antibiotic use overall.
We aim to determine whether short-duration antibiotic treatment is as good as routine practice, which is usually a longer duration of antibiotics, for critically ill patients with sepsis.
We will carry out a clinical trial including adult patients with sepsis who are admitted to a critical care unit. We will randomly allocate patients to receive a short fixed-course of antibiotics (5 days) or usual care (this is typically a 9-day course). This trial will only specify the duration of antibiotics, and the clinical team will know what duration the patient is getting. The choice or combination of antibiotics will be decided by the clinical team. All patients will have antibiotics managed according to standard antibiotic stewardship practice. The only difference between the two trial groups is that the short-duration group will have 5 days of antibiotics.
We will determine whether short-course antibiotic treatment is as effective as routine practice by assessing clinical outcomes for patients when they are in hospital and at 90-day follow-up.
Who can participate?
The SHORTER trial will recruit adults patients (aged 18 or over) who are being treated in a critical care setting for suspected or confirmed sepsis.
What does the study involve?
Antibiotics are essential in treating sepsis. But we also know that there are side effects of being treated with antibiotics, especially in people being treated in an intensive care setting. These include developing more infections, some of these might not respond to antibiotic treatment, and side effects in the body especially the kidneys. Commonly antibiotics are given for 7 or more days to treat sepsis. In the SHORTER trial we want to know whether we can safely and effectively treat sepsis with a shorter 5-day course of antibiotics and what effect this would have on patients.
Participants hospital stay will not change at all. Participants will be selected at random, by a computer, to take part in the intervention arm or control arm of the trial. If taking part in the intervention arm participants will have a short 5 day course of antibiotics to treat their sepsis, if taking part on the control arm participants will have the length of their antibiotics chosen by their hospital team, typically this will be 7 or more days of antibiotics.
Participants will take part in the trial for up to 90 days (approximately 3 months). Up to 90 days data will be collected from participants’ medical records. At 90 days participants will be contacted and asked to complete some trial questionnaires.
What are the potential benefits and risks of participating?
Participants may experience some potential benefits but it is also possible that they do not have any direct benefit. Though, participation could influence the treatment patients with sepsis receive in the future.
The main risk is if antibiotics are stopped before the infection is treated fully. Hospital teams will monitor participants’ health closely, as they would normally, to ensure that they are not put at risk. If participants need to continue receiving antibiotics for longer, then they will be given these without hesitation. Participant safety always comes first. If this does happen data will still be used for the trial.
Where is the study run from?
The Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
February 2023 to May 2028
Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK).
Who is the main contact?
SHORTER.Trial@newcastle.ac.uk
Contact information
Scientific
Newcastle Clinical Trials Unit, Newcastle University, 1-4 Claremont Terrace
Newcastle upon Tyne
NE2 4AE
United Kingdom
 ORCID ID |
0000-0002-1253-6668 |
|---|---|
| Phone | +44 191 208 3819 |
| SHORTER.Trial@newcastle.ac.uk |
Scientific
Newcastle Clinical Trials Unit, Newcastle University, 1-4 Claremont Terrace
Newcastle-upon-Tyne
NE2 4AE
United Kingdom
| ORCID ID |
0000-0002-2056-5047 |
|---|---|
| Phone | +44 191 208 2422 |
| SHORTER.Trial@newcastle.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Interventional randomized controlled trial |
| Secondary study design | Randomised controlled trial |
| Scientific title | A randomised controlled trial of SHORT duration antibiotic thERapy for critically ill patients with sepsis |
| Study acronym | SHORTER |
| Study objectives | Current study objectives as of 06/11/2025: 1. To determine whether short duration antibiotic therapy is as good as standard care in treating sepsis in terms of mortality and whether it reduces overall antibiotic exposure. 2. To assess the effect of short duration antibiotic therapy on: 2.1. Suspected clinically relevant antibiotic-associated adverse events 2.2. Length of critical care unit stay 2.3. Length of hospital-stay 2.4. Rate of further/recurrence of infections 2.5. Readmission to critical care or hospital 3. Health Economic analysis: 3.1. Is short course antibiotic therapy cost effective compared to usual care at 90 days post intervention? 3.2. Is short course antibiotic therapy cost effective compared to usual care over the patient’s lifetime? 4. Process Evaluation: 4.1. To understand the implementation of the trial protocol and willingness of clinicians to follow a fixed short-duration intervention. _____ Previous study objectives: 1. To determine whether short duration antibiotic therapy is as good asd standard care in treating sepsis in terms of mortality and whether it reduces overall antibiotic exposure 2. To assess the effect of short duration antibiotic therapy on: 2.1. Suspected clinically relevant antibiotic-associated adverse events 2.2. Length of critical care unit stay 2.3. Length of hospital-stay 2.4. Rate of further/recurrence of infections 2.5. Readmission to critical care or hospital 3. Health Economic analysis: 3.1. Is short course antibiotic therapy cost effective compared to usual care at 90 days post intervention 3.2. Is short course antibiotic therapy cost effective compared to usual care over the patient’s lifetime 4. Process Evaluation: 4.1. To understand the implementation of the trial protocol and willingness of clinicians to follow a fixed short-duration intervention |
| Ethics approval(s) |
1. Approved 12/09/2023, Wales REC 4 (Health and Care Research Wales Support and Delivery Centre, Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, United Kingdom; +44 2922 940989; Wales.REC4@wales.nhs.uk), ref: 23/WA/0197 2. Approved 01/05/2024, Scotland A Research Ethics Committee (2nd Floor, Waverley Gate 2-4 Waterloo Place, Edinburgh, EH1 3EG, United Kingdom; +44 781 460 9032; sesres@nhslothian.scot.nhs.uk), ref: 24/SS/0013 |
| Health condition(s) or problem(s) studied | Sepsis |
| Intervention | Current interventions as of 06/11/2025: Patients will be randomised to one of two arms; the intervention arm and the comparator arm. Participants randomised to the intervention arm will have the duration of antibiotics adjusted to a 5-day course. This duration commences from the initiation of antibiotics. This short course of antibiotics relates only to the initial course of antibiotics and to its duration. The choice of antibiotics will be according to the clinical team. Duration of antibiotics in the comparator arm will be according to best practice and guidelines as per standard care. All other aspects of care between the two trial groups will be according to best practice, including antibiotic adjustments according to test results and antibiotic stewardship multi-disciplinary team involvement. Participant follow up will extend to 90-days. Outcome data will be collected from clinical records and routinely collected electronic data including Intensive Care audit bodies such as Intensive Care National Audit & Research Centre (ICNARC). The majority of outcome data will be collected before participants are discharged from hospital. Participants will be asked to complete questionnaires for health economic analysis (quality of life, time and travel) at 90 days. Participants will be contacted by telephone or post if discharged by this point. In summary, patients will be screened for eligibility and have antibiotic duration for sepsis adjusted if randomised to the intervention arm. All other aspects of routine care will be unchanged. Participants will be followed up for 90 days following randomisation. The majority of outcome data will be collected from clinical records or routine electronic data sources. Participants will be asked to complete questionnaires at 90-day follow up for health economic analysis. Process Evaluation: We will utilise mixed methods, using purposive sampled qualitative data together with quantitative data from the trial. Data will be collected during the following stages of the trial: 1. Pre-trial: We will assess the current practice of antibiotic use with a baseline questionnaire sent to all sites. 2. During the internal pilot: In a purposive sample of 10 sites (max of 40 participants) we will administer the Normalisation Measure Development survey instrument (NoMAD-23 item) and conduct interviews with clinical staff to determine the acceptability of the trial protocol. 3. During the main study: We will conduct semi-structured interviews (either face-to-face or remotely via tele/video conferencing) with clinical staff from approximately 10 sites (max of 40 participants) to assess the implementation and acceptability of the intervention and clinical decisions affecting fidelity to the trial protocol. We will also conduct non-participant observations to understand the decision-making process related to antibiotic use. 4. Final site visits: We will conduct semi-structured interviews (either face-to-face or via tele/video conferencing) with staff (max of 40 participants) in purposively selected 10 sites involved in the intervention delivery to reflect on the use of the trial protocol, including perceived barriers, enablers, and work processes affecting antibiotic prescribing practice. _____ Previous interventions as of 22/04/2024: Patients will be randomised to one of two arms; the intervention arm and the comparator arm. Participants randomised to the intervention arm, will have the duration of antibiotics adjusted to a 5-day course. This duration commences from the initiation of antibiotics. This short course of antibiotics relates only to the initial course of antibiotics and to its duration. The choice of antibiotics will be according to the clinical team. Duration of antibiotics in the comparator arm will be according to best practice and guidelines as per standard care. All other aspects of care between the two trial groups will be according to best practice, including antibiotic adjustments according to test results and antibiotic stewardship multi-disciplinary team involvement. Participant follow up will extend to 90-days. Outcome data will be collected from clinical records and routinely collected electronic data including Intensive Care audit bodies such as Intensive Care National Audit & Research Centre (ICNARC). The majority of outcome data will be collected before participants are discharged from hospital. Participants will be asked to complete questionnaires for health economic analysis (quality of life, time and travel) at 90 days. Participants will be contacted by telephone if discharged by this point. In summary, patients will be screened for eligibility and have antibiotic duration for sepsis adjusted if randomised to the intervention arm. All other aspects of routine care will be unchanged. Participants will be followed up for 90 days following randomisation. The majority of outcome data will be collected from clinical records or routine electronic data sources. Participants will be asked to complete questionnaires at 90-day follow up for health economic analysis. Process Evaluation: We will utilise mixed methods, using purposive sampled qualitative data together with quantitative data from the trial. Data will be collected during the following stages of the trial: 1. Pre-trial: We will assess the current practice of antibiotic use with a baseline questionnaire sent to all 50 sites. 2. During the internal pilot: In a purposive sample of 10 sites (max of 40 participants) we will administer the Normalisation Measure Development survey instrument (NoMAD-23 item) and conduct interviews with clinical staff to determine the acceptability of the trial protocol. 3. During the main study: We will conduct semi-structured interviews (either face-to-face or remotely via tele/video conferencing) with clinical staff from approximately 10 sites (max of 40 participants) to assess the implementation and acceptability of the intervention and clinical decisions affecting fidelity to the trial protocol. We will also conduct non-participant observations to understand the decision-making process related to antibiotic use. 4. Final site visits: We will conduct semi-structured interviews (either face-to-face or via tele/video conferencing) with staff (max of 40 participants) in purposively selected 10 sites involved in the intervention delivery to reflect on the use of the trial protocol, including perceived barriers, enablers, and work processes affecting antibiotic prescribing practice. _____ Previous interventions: Patients will be randomised to one of two arms; the intervention arm and the comparator arm. Participants randomised to the intervention arm, will have the duration of antibiotics adjusted to a 5-day course. This duration commences from the initiation of antibiotics. This short course of antibiotics relates only to the initial course of antibiotics and to its duration. The choice of antibiotics will be according to the clinical team. Duration of antibiotics in the comparator arm will be according to best practice and guidelines as per standard care. All other aspects of care between the two trial groups will be according to best practice, including antibiotic adjustments according to test results and antibiotic stewardship multi-disciplinary team involvement. Participant follow up will extend to 90-days. Outcome data will be collected from clinical records and routinely collected electronic data including the Hospital Episode Statistics (HES), Office for National Statistics (ONS) and Intensive Care audit bodies such as Intensive Care National Audit & Research Centre (ICNARC). The majority of outcome data will be collected before participants are discharged from hospital. Participants will be asked to complete questionnaires for health economic analysis (quality of life, time and travel) at 90 days. Participants will be contacted by telephone if discharged by this point. In summary, patients will be screened for eligibility and have antibiotic duration for sepsis adjusted if randomised to the intervention arm. All other aspects of routine care will be unchanged. Participants will be followed up for 90 days following randomisation. The majority of outcome data will be collected from clinical records or routine electronic data sources. Participants will be asked to complete questionnaires at 90-day follow up for health economic analysis. Process Evaluation: We will utilise mixed methods, using purposive sampled qualitative data together with quantitative data from the trial. Data will be collected during the following stages of the trial: 1. Pre-trial: We will assess the current practice of antibiotic use with a baseline questionnaire sent to all 50 sites. 2. During the internal pilot: In a purposive sample of 10 sites (max of 40 participants) we will administer the Normalisation Measure Development survey instrument (NoMAD-23 item) and conduct interviews with clinical staff to determine the acceptability of the trial protocol. 3. During the main study: We will conduct semi-structured interviews (either face-to-face or remotely via tele/video conferencing) with clinical staff from approximately 10 sites (max of 40 participants) to assess the implementation and acceptability of the intervention and clinical decisions affecting fidelity to the trial protocol. We will also conduct non-participant observations to understand the decision-making process related to antibiotic use. 4. Final site visits: We will conduct semi-structured interviews (either face-to-face or via tele/video conferencing) with staff (max of 40 participants) in purposively selected 10 sites involved in the intervention delivery to reflect on the use of the trial protocol, including perceived barriers, enablers, and work processes affecting antibiotic prescribing practice. |
| Intervention type | Drug |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Antibiotics |
| Primary outcome measure(s) |
Measured using patient records: |
| Key secondary outcome measure(s) |
Current secondary outcome measures as of 06/11/2025: |
| Completion date | 31/05/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 110 Years |
| Sex | All |
| Target sample size at registration | 2244 |
| Key inclusion criteria | Current key inclusion criteria as of 06/11/2025: 1. Adult patients, aged >=18 years, treated within a critical care setting (ICU or HDU) for suspected or confirmed sepsis due to either community- or hospital-acquired infections. 2. Evidence of new or worsening acute organ dysfunction resulting from suspected or confirmed infection (e.g. the treatment or monitoring of an organ dysfunction). 3. Antibiotics initiated for suspected or confirmed sepsis, patient is still receiving antibiotics at randomisation, and is able to be randomised within 4 days of the initiation of this course of antibiotics. Process evaluation: Clinical staff involved in everyday prescribing and/or managing of antibiotics within critical care. _____ Previous key inclusion criteria: 1. Adult patients, age >=18 years, treated within a critical care setting (ICU or HDU) for suspected or confirmed sepsis due to either community- or hospital-acquired infections. 2. Evidence of new or worsening acute organ dysfunction resulting from suspected or confirmed infection (e.g. the treatment or monitoring of an organ dysfunction). 3. Antibiotics initiated for suspected or confirmed sepsis and able to be randomised within 4 days of the initiation of this course of antibiotics Process evaluation: Clinical staff involved in everyday prescribing and/or managing of antibiotics within critical care. |
| Key exclusion criteria | Current key exclusion criteria as of 06/11/2025: 1. Comorbidity with immunosuppression (e.g. Chemotherapy, maintenance steroids equivalent to > 10mg/day of prednisolone, post-transplantation). 2. Blood neutrophil count less than 0.5 x 10^9/L secondary to a pre-existing comorbidity. 3. Infection source where usual practice involves more than 14 days of antibiotics (e.g. undrainable abscess, endocarditis, Staphylococcus aureus bacteraemia, osteomyelitis). 4. Receiving end-of-life care. 5. Life-sustaining treatment expected to be withdrawn within the next 24 hours. 6. The clinician responsible for the patient’s care is unable to adhere to the intervention. 7. Concomitant enrolment in another interventional trial, except where a co-enrolment agreement with SHORTER exists. _____ Previous key exclusion criteria: 1. Comorbidity with immunosuppression (e.g. Chemotherapy, maintenance steroids equivalent to > 10mg/day of prednisolone, post-transplantation) 2. Blood neutrophil count less than 0.5 x 10^9/L secondary to a pre-existing comorbidity 3. Infection source where usual practice involves more than 14 days of antibiotics (e.g. undrainable abscess, endocarditis, Staphylococcus aureus bacteraemia, osteomyelitis) 4. Receiving end-of-life care 5. Life-sustaining treatment expected to be withdrawn within the next 24 hours. 6. The clinician responsible for the patient’s care is unable to adhere to the intervention. The following participant exclusion criteria was added on 03/03/2025: 7. Concomitant enrolment in another interventional trial, except where a co-enrolment agreement with SHORTER exists (a list of interventional trials approved for co-enrolment can be found on the trial website: https://www.shortertrial.com/). |
| Date of first enrolment | 30/11/2023 |
| Date of final enrolment | 30/06/2027 |
Locations
Countries of recruitment
- United Kingdom
- England
- Northern Ireland
- Scotland
- Wales
Study participating centres
London
N19 5NF
England
De Crespigny Park
Denmark Hill
London
SE5 8AB
England
Orpington
BR6 8ND
England
Ipswich
IP4 5PD
England
High Heaton
Newcastle upon Tyne
NE7 7DN
England
Newcastle upon Tyne
NE1 4LP
England
Cambridge Biomedical Campus
Cambridge
CB2 0AY
England
Sunderland
SR4 7TP
England
Cramlington
NE23 6NZ
England
Standing Way
Eaglestone
Milton Keynes
MK6 5LD
England
Romford
RM7 0AG
England
Northampton
NN1 5BD
England
Rotherham
S60 2UD
England
Willesborough
Ashford
TN24 0LZ
England
Odstock Road
Salisbury
SP2 8BJ
England
Truro
TR1 3LJ
England
Blackshaw Road
London
SW17 0QT
England
Taunton
TA1 5DA
England
Wakefield
WF1 4DG
England
Yeovil
BA21 4AT
England
Harrow
HA1 3UJ
England
Bath
BA1 3NG
England
Bodelwyddan
Rhyl
LL18 5UJ
Wales
Durham
DH1 5TW
England
Gateshead
NE9 6SX
England
Oldham
OL1 2JH
England
Old Dalkeith Road
Edinburgh
Lothian
EH16 4SA
Scotland
Howden
Livingston
West Lothian
Edinburgh
EH54 6PP
Scotland
Edinburgh
Lothian
EH4 2XU
Scotland
Dundonald
Belfast
BT16 1RH
Northern Ireland
Shrewsbury
SY3 8XQ
England
Lewes Road
Haywards Heath
RH16 4EX
England
Glasgow
G4 0SF
Scotland
Wythenshawe
Manchester
M23 9LT
England
Hills Road
Cambridge
CB2 0QQ
England
Manchester
M13 9WL
England
Crumpsall
Manchester
M8 5RB
England
Harlow
CM20 1QX
England
Antrim
BT41 2RL
Northern Ireland
Birmingham
B18 7QH
England
Stoke-on-trent
ST4 6QG
England
Liverpool
L9 7AL
England
Sutton Coldfield
B75 7RR
England
Bordesley Green
Birmingham
B9 5SS
England
Liverpool
L7 8XP
England
Warwick
CV34 5BW
England
Wexham
Slough
SL2 4HL
England
Duckworth Lane
Bradford
BD9 6RJ
England
Burton-on-trent
DE13 0RB
England
Londonderry
BT47 6SB
Northern Ireland
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan | Data from this trial will be available to the scientific community subject to request and appropriate ethical approval. Requests for data should be directed to the Chief Investigator and Newcastle Clinical Trials Unit. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
13/04/2026: The following changes were made:
1. Date of final enrolment was changed from 30/04/2026 to 30/06/2027.
2. Completion date was changed from 31/08/2026 to 31/05/2028.
06/11/2025: The following changes were made to the trial record:
1. The study objectives were changed.
2. The ethics approval (2) was added.
3. The interventions were changed.
4. The secondary outcome measures were changed.
5. The key inclusion criteria were changed.
6. The key exclusion criteria were changed.
7. The study participating centres were updated.
8. The plain English summary was updated to reflect these changes.
15/09/2025: The study participating centre Queen's Hospital was added.
12/09/2025: The study participating centres were relisted in order of opening to recruitment: Whittington Hospital, King's College Hospital, Princess Royal University Hospital, The Ipswich Hospital, Freeman Hospital, Newcastle, Royal Victoria Infirmary, Newcastle, Royal Papworth Hospital, Sunderland Royal Hospital, Northumbria Specialist Emergency Care Hospital, Milton Keynes General Hospital, Queens Hospital, Romford, Northampton General Hospital, Rotherham General Hospital, William Harvey Hospital, Salisbury District Hospital, Leeds General Infirmary, Royal Cornwall Hospital, St George's Hospital, Musgrove Park Hospital, Pinderfields Hospital, Yeovil District Hospital, Northwick Park Hospital, Royal United Hospital, Glan Clwyd District General Hospital, University Hospital of North Durham, Queen Elizabeth Hospital, Gateshead, The Royal Oldham Hospital, Royal Infirmary Edinburgh, St John's Hospital, Western General Hospital, Ulster Hospital, Royal Shrewsbury Hospital, Princess Royal Hospital, Glasgow Royal Infirmary, Wythenshawe Hospital, Addenbrooke's Hospital, Manchester Royal Infirmary, North Manchester General Hospital, The Princess Alexandra Hospital, Antrim Hospital, City and Sandwell Hospital, Royal Stoke University Hospital, Aintree University Hospital, Good Hope Hospital, Heartlands Hospital, Royal Liverpool University Hospital, Warwick Hospital, Wexham Park Hospital, and Bradford Royal Infirmary.
10/09/2025: The following changes were made:
1. Date of final enrolment was changed from 30/09/2025 to 30/04/2026.
2. England, Scotland, Northern Ireland and Wales were added as countries of recruitment.
03/03/2025: An additional participant exclusion criterion was added.
20/09/2024: The participant level data sharing statement was added.
22/04/2024: The interventions were changed.
19/02/2024: The ethics approval was added.
07/11/2023: Trial's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).
