Sepsis1BEDNCT05273034
Effect of the 1-hour Sepsis Bundle on In-hospital Mortality in Patients With Sepsis in the Emergency Department
A study testing 1-hour sepsis bundle in people with Sepsis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Reducing the mortality and morbidity of sepsis is a worldwide priority for almost 20 years. Since an observational study in the NY state, which reported in-hospital mortality increased, associated with each supplemental hour to complete the sepsis bundle, SSC guidelines have decided in 2018 to recommend a short… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- 1-hour sepsis bundle
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 873 participants
- Where
- 1 siteFrance
- Study dates
- 13 Jun 2022to 13 Oct 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ED adult patients, with suspected infection
- Free given Oral consent given by the patient or by the trustworthy person / family member / close relative or inclusion in case of emergency.
- AND at least one of the following:
- Serum lactate > 2.0 mmol/l
- Systolic blood pressure < 90 mmHg
- Suspicion of sepsis as defined by the SEPSIS-3 International consensus: life threatening organ dysfunction identified by a SOFA score of 2 at least or a quick SOFA score of 2 at least (altered consciousness, systolic blood pressure < 100 mmHg, respiratory rate > 22)
- For French sites, free given Oral consent given by the patient or by the trustworthy person / family member / close relative or inclusion in case of emergency. According to the Biomedical Research Law 14/2007 in Spain, the emergency consent is not apply. The written patient consent is mandatory.
Who cannot join
- Patient living in assisted-living home or nursing home or palliative center
- Patient under legal protection measure (tutorship or curatorship) and patient deprived of freedom
- Anticipated life expectancy < 3 months or "do not resuscitate" order
- Known acute heart failure
- No social security
- Pregnancy and breastfeeding
Show all 10Show fewer
- Prisoners
- Participation in another interventional trial (RIPH 1 et 2)
- Patients that presented inclusion criteria more than 3 hours before inclusion
- Patient in whom antibiotics or fluid resuscitation has been started before inclusion
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of the 1-hour Sepsis Bundle on In-hospital Mortality in Patients With Sepsis in the Emergency Department: a Randomized Controlled Trial
Reducing the mortality and morbidity of sepsis is a worldwide priority for almost 20 years. Since an observational study in the NY state, which reported in-hospital mortality increased, associated with each supplemental hour to complete the sepsis bundle, SSC guidelines have decided in 2018 to recommend a short timeframe of 1-h to complete the sepsis bundle. This new recommendation is vividly debated due to a lack of evidences of its relevance. No trial has ever studied a sepsis intervention when applied as early as Emergency Department ED triage (newly recommended 1-h sepsis bundle consider time zero as time of ED triage).
The aim of this trial is to demonstrate that the early implementation at ED triage of the 1-hour bundle by ED physicians improves in-hospital mortality in patients with sepsis, and therefore provides the required robust evidence for the SSC guidance to enhance physicians and stakeholder adherence.
Read more
This is a superiority, international multicenter, open trial with a stepped wedge randomisation.
All centers will recruit adult emergency patients with suspicion of sepsis as defined by a suspicion of infection and suspicion of life threatening organ dysfunction (quick SOFA or SOFA ≥ 2, hypotension or hyperlactatemia).
According to the center period, the management of sepsis patients will be based either following the current recommended 1-hour sepsis bundle (intervention group) or at the discretion of the treating ED physician as in current routine practice (control group). There is no intervention that is "added" by the research.
Read the detailed description
In Europe, one third of patients with sepsis and septic shock are admitted through the emergency department (ED), with an overall in-hospital mortality of 20%, and 90 days mortality of 25%. Reducing the mortality and morbidity of sepsis is thus a worldwide priority.
In 2016, the "Surviving Sepsis Campaign" (SSC), an international group of experts, recommended that physicians should complete the sepsis bundle in the first 3-h, which included blood culture, lactate measurement, broad spectrum antibiotics, and 30ml/kg fluid resuscitation in case of hypotension. Subsequently to the publication of a large retrospective study in NYC that reported a higher risk of mortality for each additional hour to complete the sepsis bundle, the 2018 update of the SSC guidelines moved further and recommended an even shorter timeframe of 1-h from ED triage to initiate the sepsis bundle. This new recommendation is vividly debated and several scientific societies, such as the SCCM, ACEP, and EUSEM have recommended that hospitals should not implement the one-hour sepsis bundle before having more evidence. Indeed, the quality of evidence supporting this new guidance was acknowledged overall as low to moderate and as requiring confirmatory studies. Moreover, no trial has ever studied a sepsis intervention when applied as early as ED triage (newly recommended 1-h sepsis bundle consider time zero as time of ED triage).
The primary objective of this trial is thus to demonstrate that the early implementation at ED triage of the 1-hour bundle by ED physicians improves in-hospital mortality in patients with sepsis, and therefore provides the required robust evidence for the SSC guidance to enhance physicians and stakeholder adherence. In-hospital mortality has been chosen as a primary endpoint in several major trials, such as ProCESS and ANDROMEDA SCHOCK. This in-hospital mortality will be truncated at 28 days because longer term to death may not reflect an effect of an early intervention. Furthermore, it has been described that mortality that occurs after hospital discharge may not be linked with the index acute disease, but rather mostly due to comorbidities (Frog ICU) and thus less relevant for assessing the efficacy of two early interventions.
Secondary objectives include the in-hospital morbidity, antibiotic exposure and fluid resuscitation, an all cause 28-day mortality with the implementation of the 1-hour sepsis bundle at ED triage vs practice in patients with sepsis in the ED.
The recommended 1-hour sepsis bundle (intervention group) carries the risk of over-exposition to antibiotics and excessive fluids resuscitation that may contribute to acute heart failure. However, the routine practice with longer time frame to complete the bundle carries the risk of sub-optimal treatment of sepsis with potential higher risk of mortality. Equipoise remains on which strategy carries the higher risk. Data from one large observational study suggest that each additional hour to the 1-hour sepsis bundle could increase mortality by an adjusted Odds Ratio of 1.04 (1.03 - 1.06).
This study will include patients that present to an ED with a suspicion of sepsis, as defined by the SEPSIS-3 consensus.
All centers will start in the control group for 4 weeks. Then, after every step of 4 weeks, two centers will switch to the intervention group, i.e. implementation at ED triage of the 1-h sepsis bundle. After the last center has switched for the intervention period, a last step of 4 weeks with all center in the intervention will be added. The order in which EDs will switch to the intervention will be randomized before the start of the trial.
The total duration of the study is planned to be 12 months (52 weeks) and 28 days with 24 centers expected.
Each participant with a suspicion of sepsis will be included and followed-up until hospital discharge at 28 days, whichever comes first. A follow-up at day 3 will be realised in order to collect components of the SOFA score and ICU status, and other secondary endpoints. If the patient is discharged before day 3, the last available hospital value will be used to calculate the SOFA score. The vital status of the patient will be assessed at day 28 or day of discharge alive.
Analysis will be performed at the end of the study after data review and before data base lock according to Intent to treat principle and with regard to cluster level randomisation.
- Conditions
- Sepsis
- Being tested
- 1-hour sepsis bundle
- Keywords
- Sepsis, 1-hour sepsis bundle, Emergency department
- Medical subject headings
- Sepsis, Emergencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1-hour sepsis bundleProcedure or surgery
The sepsis management will be delivered in a timely manner within 60 minutes of ED triage including
- usual test and treatment
- blood culture
- lactate measurement
- broad spectrum antibiotics
- In case of hypotension or lactate > 4, rapid administration of 30ml/kg crystalloid fluid resuscitation will be mandated
- In case of initial elevated lactate (> 2 mmol/l), a second lactate measurement should be done after initial fluid resuscitation.
| Study group | Role | What they receive |
|---|---|---|
| 1-h sepsis bundle | Experimental | Not described Receives: Procedure: 1-hour sepsis bundle |
| Current practice | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
In-hospital mortality
Safety Issue ? : Yes / No
Measured: truncated at day 28
Secondary outcomes (7)
Amount of fluid resuscitation
Measured: in the first 24 hours
Acute heart failure
Acute heart failure defined by clinical signs of acute heart failure associated with either elevated brain natriuretic peptide or signs of pulmonary edema on chest imaging
Measured: During the first 24 hours
SOFA score
If the patient is discharged before day 3, the last available hospital value will be used to calculate the SOFA score.
Measured: Up to 3 days
ICU length of stay
Measured: Up to 3 days
Total number of days under mechanical ventilation, renal replacement therapy, and vasopressor-free
Will be considered only during index hospitalisation
Measured: within 28 days
Undue antibiotic administration
defined by introduction of antibiotic in the ED for patients in whom infectious disease was ruled out during hospital course
Measured: Up to 3 days
Mortality
death from all cause
Measured: at day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2022
- Study start13 Jun 2022
- Primary completion13 Oct 2023
- Study completion13 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 873 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yonathan FREUND, PU-PH, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05273034
- Sponsor's protocol ID
- APHP211023
- Other IDs
- IDRCB 2021-A01937-34
- Acronym
- 1BED
- Status last verified
- Feb 2024
- First submitted
- 9 Feb 2022
- Last updated
- 26 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Freund Y, Cancella de Abreu M, Lebal S, Rousseau A, Lafon T, Yordanov Y, Macrez R, Coisy F, Le Borgne P, Femy F, Douillet D, Boter NR, Eyer X, Bouillon-Minois JB, Ogereau C, Bouzid D, Goulet H, Roussel M, Rousseau G, Guenezan J, Occelli C, Chouihed T, Osorio Quispe G, Renard MC, Gorlicki J, Bloom B, Simon T, Gerlier C. Effect of the 1-h bundle on mortality in patients with suspected sepsis in the emergency department: a stepped wedge cluster randomized clinical trial. Intensive Care Med. 2024 Jul;50(7):1086-1095. doi: 10.1007/s00134-024-07509-1. Epub 2024 Jun 24.
PubMed 38913098
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of the 1-hour Sepsis Bundle on In-hospital Mortality in Patients With Sepsis in the Emergency Department: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05273034
- Acronym / sponsor ID
- 1BED / APHP211023
- Conditions
- Sepsis
- Keywords
- Sepsis, 1-hour sepsis bundle, Emergency department
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 873 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 13 Jun 2022 (actual)
- Primary completion
- 13 Oct 2023 (actual)
- Study completion
- 13 Oct 2023 (actual)
- First posted
- 10 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Reducing the mortality and morbidity of sepsis is a worldwide priority for almost 20 years. Since an observational study in the NY state, which reported in-hospital mortality increased, associated with each supplemental hour to complete the sepsis bundle, SSC guidelines have decided in 2018 to recommend a short timeframe of 1-h to complete the sepsis bundle. This new recommendation is vividly debated due to a lack of evidences of its relevance. No trial has ever studied a sepsis intervention when applied as early as Emergency Department ED triage (newly recommended 1-h sepsis bundle consider time zero as time of ED triage).
The aim of this trial is to demonstrate that the early implementation at ED triage of the 1-hour bundle by ED physicians improves in-hospital mortality in patients with sepsis, and therefore provides the required robust evidence for the SSC guidance to enhance physicians and stakeholder adherence.
This is a superiority, international multicenter, open trial with a stepped wedge randomisation.
All centers will recruit adult emergency patients with suspicion of sepsis as defined by a suspicion of infection and suspicion of life threatening organ dysfunction (quick SOFA or SOFA ≥ 2, hypotension or hyperlactatemia).
According to the center period, the management of sepsis patients will be based either following the current recommended 1-hour sepsis bundle (intervention group) or at the discretion of the treating ED physician as in current routine practice (control group). There is no intervention that is "added" by the research.
Detailed description
In Europe, one third of patients with sepsis and septic shock are admitted through the emergency department (ED), with an overall in-hospital mortality of 20%, and 90 days mortality of 25%. Reducing the mortality and morbidity of sepsis is thus a worldwide priority.
In 2016, the "Surviving Sepsis Campaign" (SSC), an international group of experts, recommended that physicians should complete the sepsis bundle in the first 3-h, which included blood culture, lactate measurement, broad spectrum antibiotics, and 30ml/kg fluid resuscitation in case of hypotension. Subsequently to the publication of a large retrospective study in NYC that reported a higher risk of mortality for each additional hour to complete the sepsis bundle, the 2018 update of the SSC guidelines moved further and recommended an even shorter timeframe of 1-h from ED triage to initiate the sepsis bundle. This new recommendation is vividly debated and several scientific societies, such as the SCCM, ACEP, and EUSEM have recommended that hospitals should not implement the one-hour sepsis bundle before having more evidence. Indeed, the quality of evidence supporting this new guidance was acknowledged overall as low to moderate and as requiring confirmatory studies. Moreover, no trial has ever studied a sepsis intervention when applied as early as ED triage (newly recommended 1-h sepsis bundle consider time zero as time of ED triage).
The primary objective of this trial is thus to demonstrate that the early implementation at ED triage of the 1-hour bundle by ED physicians improves in-hospital mortality in patients with sepsis, and therefore provides the required robust evidence for the SSC guidance to enhance physicians and stakeholder adherence. In-hospital mortality has been chosen as a primary endpoint in several major trials, such as ProCESS and ANDROMEDA SCHOCK. This in-hospital mortality will be truncated at 28 days because longer term to death may not reflect an effect of an early intervention. Furthermore, it has been described that mortality that occurs after hospital discharge may not be linked with the index acute disease, but rather mostly due to comorbidities (Frog ICU) and thus less relevant for assessing the efficacy of two early interventions.
Secondary objectives include the in-hospital morbidity, antibiotic exposure and fluid resuscitation, an all cause 28-day mortality with the implementation of the 1-hour sepsis bundle at ED triage vs practice in patients with sepsis in the ED.
The recommended 1-hour sepsis bundle (intervention group) carries the risk of over-exposition to antibiotics and excessive fluids resuscitation that may contribute to acute heart failure. However, the routine practice with longer time frame to complete the bundle carries the risk of sub-optimal treatment of sepsis with potential higher risk of mortality. Equipoise remains on which strategy carries the higher risk. Data from one large observational study suggest that each additional hour to the 1-hour sepsis bundle could increase mortality by an adjusted Odds Ratio of 1.04 (1.03 - 1.06).
This study will include patients that present to an ED with a suspicion of sepsis, as defined by the SEPSIS-3 consensus.
All centers will start in the control group for 4 weeks. Then, after every step of 4 weeks, two centers will switch to the intervention group, i.e. implementation at ED triage of the 1-h sepsis bundle. After the last center has switched for the intervention period, a last step of 4 weeks with all center in the intervention will be added. The order in which EDs will switch to the intervention will be randomized before the start of the trial.
The total duration of the study is planned to be 12 months (52 weeks) and 28 days with 24 centers expected.
Each participant with a suspicion of sepsis will be included and followed-up until hospital discharge at 28 days, whichever comes first. A follow-up at day 3 will be realised in order to collect components of the SOFA score and ICU status, and other secondary endpoints. If the patient is discharged before day 3, the last available hospital value will be used to calculate the SOFA score. The vital status of the patient will be assessed at day 28 or day of discharge alive.
Analysis will be performed at the end of the study after data review and before data base lock according to Intent to treat principle and with regard to cluster level randomisation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1-h sepsis bundle | Experimental | Procedure: 1-hour sepsis bundle |
| Current practice | No intervention | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- ED adult patients, with suspected infection
- Free given Oral consent given by the patient or by the trustworthy person / family member / close relative or inclusion in case of emergency.
- Serum lactate > 2.0 mmol/l
- Systolic blood pressure < 90 mmHg
- Suspicion of sepsis as defined by the SEPSIS-3 International consensus: life threatening organ dysfunction identified by a SOFA score of 2 at least or a quick SOFA score of 2 at least (altered consciousness, systolic blood pressure < 100 mmHg, respiratory rate > 22)
Key exclusion criteria (10 listed)
- Patient living in assisted-living home or nursing home or palliative center
- Patient under legal protection measure (tutorship or curatorship) and patient deprived of freedom
- Anticipated life expectancy < 3 months or "do not resuscitate" order
- Known acute heart failure
- No social security
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1-hour sepsis bundleThe sepsis management will be delivered in a timely manner within 60 minutes of ED triage including * usual test and treatment * blood culture * lactate measurement * broad spectrum antibiotics * In case of hypotension or lactate > 4, rapid administration of 30ml/kg crystalloid fluid resuscitation will be mandated * In case of initial elevated lactate (> 2 mmol/l), a second lactate measurement should be done after initial fluid resuscitation. | Procedure or surgery | 1-h sepsis bundle |
Primary outcome
In-hospital mortality
Time frame: truncated at day 28
Safety Issue ? : Yes / No
7 secondary outcomes
Amount of fluid resuscitation
Time frame: in the first 24 hours
Acute heart failure
Time frame: During the first 24 hours
SOFA score
Time frame: Up to 3 days
ICU length of stay
Time frame: Up to 3 days
Total number of days under mechanical ventilation, renal replacement therapy, and vasopressor-free
Time frame: within 28 days
Undue antibiotic administration
Time frame: Up to 3 days
Mortality
Time frame: at day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2024.
- Derived from this study: PubMed 38913098Freund Y, Cancella de Abreu M, Lebal S, Rousseau A, Lafon T, Yordanov Y, Macrez R, Coisy F, Le Borgne P, Femy F, Douillet D, Boter NR, Eyer X, Bouillon-Minois JB, Ogereau C, Bouzid D, Goulet H, Roussel M, Rousseau G, Guenezan J, Occelli C, Chouihed T, Osorio Quispe G, Renard MC, Gorlicki J, Bloom B, Simon T, Gerlier C. Effect of the 1-h bundle on mortality in patients with suspected sepsis in the emergency department: a stepped wedge cluster randomized clinical trial. Intensive Care Med. 2024 Jul;50(7):1086-1095. doi: 10.1007/s00134-024-07509-1. Epub 2024 Jun 24.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yonathan FREUND, PU-PH principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 1-hour sepsis bundle in people with Sepsis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
In-hospital mortality (time frame: truncated at day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05273034, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2024.