Sepsis Bundle for Sepsis

(AIMS Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Mitchell Levy, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Rhode Island Hospital

Disqualifiers: Pregnancy, Hospital transfers, Moribund, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Since the introduction of sepsis bundles, there have been multiple published trials that have demonstrated a consistent, strong association between implementation of sepsis "bundles" (3-hour bundle) and improved survival. The current proposal is a Hybrid 2, pragmatic, cluster randomized clinical effectiveness/implementation trial evaluating mortality and respiratory failure-based outcomes, in patients admitted to the emergency department with sepsis, comparing the effectiveness of implementation of the hour-1 bundle to 3-hour bundle, while facilitating adherence to both bundles. In addition, 4 distinct sepsis phenotypes will be derived from routine clinical data to identify specific patient phenotypes that allow for a more precision-based application of sepsis bundles in future studies.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Sepsis Bundle for sepsis?

Research shows that patients with severe sepsis who received the complete 3-hour bundle had better survival rates in the hospital compared to those who did not. Additionally, adherence to sepsis bundles has been linked to reduced death rates in severe sepsis and septic shock patients. ^{1 2 3 4 5}

Is the Sepsis Bundle safe for humans?

The Sepsis Bundle, including the Hour-1 and 3-Hour Bundles, is used in emergency settings to manage sepsis, but the available research primarily focuses on its effectiveness rather than safety. There is no specific safety data mentioned in the studies, but these bundles are widely implemented in clinical practice, suggesting they are generally considered safe. ^{1 6 7 8 9}

How is the Sepsis Bundle treatment different from other sepsis treatments?

The Sepsis Bundle, including the Hour-1 and 3-Hour Bundles, is unique because it emphasizes rapid, early intervention within the first few hours of sepsis diagnosis, focusing on timely administration of antibiotics, lactate measurement, and blood culture collection. This approach aims to improve survival rates by addressing sepsis aggressively and promptly, which is different from more traditional, less time-sensitive treatments. ^{1 6 10 11 12}

Eligibility Criteria

This trial is for adults over 18 who arrive at the emergency department with sepsis within 6 hours of triage. They must meet specific criteria including infection signs, systemic inflammation response, and organ dysfunction. Pregnant women, patients transferred from other hospitals, those receiving end-of-life care within 6 hours of ED admission or previously admitted for the same condition are excluded.

Inclusion Criteria

I am 18 years old or older.

I was diagnosed with sepsis within 6 hours of arriving at the emergency department.

Exclusion Criteria

Last admission for patients admitted to same hospital once

All transfers from another hospital

I was placed on comfort care within 6 hours of being admitted to the emergency department.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the Hour-1 or 3-Hour sepsis bundle interventions

3 hours

Continuous monitoring in the emergency department

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

Implementation Evaluation

Evaluation of bundle adherence and effectiveness using the EPIS model

Ongoing throughout the trial

Treatment Details

Interventions

• Sepsis Bundle (Behavioural Intervention)

Trial Overview The study compares two methods of treating sepsis in an emergency setting: a '1-hour bundle' versus a '3-hour bundle'. It aims to see which method is more effective at reducing mortality and respiratory failure. The trial also seeks to identify patient subtypes that respond best to these treatments using data-driven phenotyping.

Participant Groups

Group I: Hour-1 Bundle Active Control 1 Intervention

If the patient meets 2+ SIRS and chief complaint criteria, a second BPA may be triggered, which displays to the provider. The second alert identifies patients who progress to organ failure based on lab results, or who have a recorded instance of hypotension. When this alert appears, an automatic counter will begin and serve as our Sepsis Time Zero. The provider will receive sepsis order sets and guided to the Sepsis Navigator. The navigator will allow them to review relevant patient data, reference sepsis guidelines, and keep tabs on a live-updating sepsis checklist to ensure they complete each element in order and on time. Following identification in the ED, both study arms will receive the same bundle (see below). The only difference will be the timing: For the Hour-1 bundle, all interventions in the bundle must be initiated within 1 hour.

Group II: 3-Hour Bundle Active Control 1 Intervention

If the patient meets 2+ SIRS and chief complaint criteria, a second BPA may be triggered, which displays to the provider. The second alert identifies patients who progress to organ failure based on lab results, or who have a recorded instance of hypotension. When this alert appears, an automatic counter will begin and serve as our Sepsis Time Zero. The provider will receive sepsis order sets and guided to the Sepsis Navigator. The navigator will allow them to review relevant patient data, reference sepsis guidelines, and keep tabs on a live-updating sepsis checklist to ensure they complete each element in order and on time. Following identification in the ED, both study arms will receive the same bundle (see below). The only difference will be the timing: For the 3-hour bundle, all elements must be completed by 3 hours.

Sepsis Bundle is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as SEP-1 Bundle for:

• Sepsis
• Septic Shock

🇪🇺 Approved in European Union as Sepsis Bundle for:

• Sepsis
• Septic Shock

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Rhode Island Hospital Providence, RI

Who Is Running the Clinical Trial?

Rhode Island Hospital Lead Sponsor

References

1. China pubmed.ncbi.nlm.nih.gov

[Application effect of 1-hour bundle in the treatment of patients with sepsis]. [2020] To investigate the implementation and application effect of 1-hour bundle in the treatment of patients with sepsis.

2. United States pubmed.ncbi.nlm.nih.gov

Severe sepsis 3-hour bundle compliance and mortality. [2019] Severe sepsis is a major cause of mortality among hospitalized patients. We tracked severe sepsis 3-hour bundle compliance and mortality over time. Those patients with severe sepsis who received the entire bundle had improved in-hospital survivability over those patients who did not receive the bundle.

3. United States pubmed.ncbi.nlm.nih.gov

Timeline of sepsis bundle component completion and its association with septic shock outcomes. [2021] To assess the impact of the timeline of sepsis bundle completion with clinical outcomes in septic shock.

4. United States pubmed.ncbi.nlm.nih.gov

Guideline bundles adherence and mortality in severe sepsis and septic shock. [2022] Surviving Sepsis Campaign bundles have been associated with reduced mortality in severe sepsis and septic shock patients. Case-mix adjusted mortality evaluations have not been performed to compare hospitals participating in sepsis bundle programs with those not participating. We aimed to achieve an individual bundle target adherence more than 80% and a relative mortality reduction of at least 15% (absolute mortality reduction 5.2%) at the end of 2012.

5. United States pubmed.ncbi.nlm.nih.gov

Impact of the Surviving Sepsis Campaign protocols on hospital length of stay and mortality in septic shock patients: results of a three-year follow-up quasi-experimental study. [2022] To describe the effectiveness of the Surviving Sepsis Campaign bundles with regard to both implementation and outcome in patients with septic shock and to determine the contribution of the various elements of the bundles to the outcome.

6. United States pubmed.ncbi.nlm.nih.gov

The 28-Day Mortality Outcome of the Complete Hour-1 Sepsis Bundle in the Emergency Department. [2023] The Surviving Sepsis Campaign published the Hour-1 Sepsis Bundle in 2018. The first-hour management of patients with sepsis in the emergency department (ED) is important, as suggested in the Hour-1 Sepsis Bundle. The objectives of the present study were to evaluate 28-day mortality and delayed septic shock with use of a complete and incomplete Hour-1 Sepsis Bundle in the ED.

7. United States pubmed.ncbi.nlm.nih.gov

Challenging the One-hour Sepsis Bundle. [2020] In April 2018, the Surviving Sepsis Campaign (SSC) released an updated sepsis bundle, which combines directives previously listed in the three-hour and six-hour bundles. The authors discussed the reasoning and evidence supporting these changes. However, there are data that suggest these recommendations may be contrary to the best available evidence. Our purpose here is to highlight the areas where evidence is only as strong as the methodological constructs of the research used. This article is a narrative review of the available, limited evidence on which the one-hour bundle was based.

8. United States pubmed.ncbi.nlm.nih.gov

Delay Within the 3-Hour Surviving Sepsis Campaign Guideline on Mortality for Patients With Severe Sepsis and Septic Shock. [2022] To specify when delays of specific 3-hour bundle Surviving Sepsis Campaign guideline recommendations applied to severe sepsis or septic shock become harmful and impact mortality.

9. England pubmed.ncbi.nlm.nih.gov

Assessment of implementation methods in sepsis: study protocol for a cluster-randomized hybrid type 2 trial. [2023] Sepsis is the leading cause of intensive care unit (ICU) admission and ICU death. In recognition of the burden of sepsis, the Surviving Sepsis Campaign (SSC) and the Institute for Healthcare Improvement developed sepsis "bundles" (goals to accomplish over a specific time period) to facilitate SSC guideline implementation in clinical practice. Using the SSC 3-h bundle as a base, the Centers for Medicare and Medicaid Services developed a 3-h sepsis bundle that has become the national standard for early management of sepsis. Emerging observational data, from an analysis conducted for the AIMS grant application, suggest there may be additional mortality benefit from even earlier implementation of the 3-h bundle, i.e., the 1-h bundle.

10. United States pubmed.ncbi.nlm.nih.gov

Hour-1 bundle adherence was associated with reduction of in-hospital mortality among patients with sepsis in Japan. [2022] The updated Surviving Sepsis Campaign guidelines recommend a 1-hour window for completion of a sepsis care bundle; however, the effectiveness of the hour-1 bundle has not been fully evaluated. The present study aimed to evaluate the impact of hour-1 bundle completion on clinical outcomes in sepsis patients.

11. United States pubmed.ncbi.nlm.nih.gov

Evaluating the impact of severe sepsis 3-hour bundle compliance on 28-day in-hospital mortality: A propensity adjusted, nested case-control study. [2022] The Centers for Medicare and Medicaid Services Severe Sepsis and Septic Shock Management Bundle (SEP-1) assesses antibiotic administration, lactate measurement, and blood culture collection within 3 h of severe sepsis onset. The impact of the SEP-1 3-hour bundle among patients with severe sepsis is not extensively described. This investigation aimed to describe the impact of 3-hour bundle compliance on 28-day in-hospital mortality in patients with severe sepsis.

12. United States pubmed.ncbi.nlm.nih.gov

Survival Benefit and Cost Savings From Compliance With a Simplified 3-Hour Sepsis Bundle in a Series of Prospective, Multisite, Observational Cohorts. [2022] To determine mortality and costs associated with adherence to an aggressive, 3-hour sepsis bundle versus noncompliance with greater than or equal to one bundle element for severe sepsis and septic shock patients.