# Assessment of Implementation Methods in Sepsis and Respiratory Failure

> **NIH NIH R01** · RHODE ISLAND HOSPITAL · 2024 · $687,161

## Abstract

Project Summary
 Sepsis is the leading cause of admission to intensive care units (ICUs) in the U.S., and the leading cause of
respiratory failure and death in ICUs. The majority of ICU patients with sepsis or septic shock have either respiratory
infection as the source of sepsis, or have respiratory failure requiring mechanical ventilation. In recognition of the burden
of sepsis in the U.S., sepsis “bundles” were introduced to facilitate guideline implementation in clinical practice (known
as the 3-Hour bundle). Since the introduction of sepsis bundles, multiple observational studies have demonstrated a
consistent, strong association between implementation of sepsis bundles and improved survival. These data led to the
New York State (NYS) Sepsis initiative, which demonstrated a significant association between adherence with sepsis
bundles and improved survival, and the Centers for Medicare and Medicaid Services (CMS) mandated public reporting
of sepsis measures (SEP-1). Analysis of the NYS database has revealed that completion of the 3-Hour bundle in
patients with respiratory failure was associated with an 8.6% absolute reduction in mortality (18.5 RRR). For those
patients who completed the 3-Hour bundle within 1 hour, the mortality reduction was even higher, 9.8% (RRR 21.7%).
In 2018, the Hour-1 bundle was published to underscore the need for urgency in the treatment of septic patients. We
believe that the primary beneficial effect of both the Hour-1 and 3-Hour bundle is in patients with respiratory failure. It is
not known if implementation of the Hour-1 bundle reduces mortality more than the 3 Hour bundle. Although adherence
with the 3-Hour bundle (SEP-1) is mandated by CMS, compliance is moderate (60%), suggesting an active
implementation process for the 3-hour bundle is necessary to compare the Hour-1 bundle to the 3-Hour bundle. The
current proposal is a pragmatic, cluster-randomized clinical trial using a hybrid type 2 effectiveness-implementation
approach to evaluate mortality and respiratory failure-based outcomes and bundle adherence, in emergency room
patients with sepsis. We will compare the hour-1 bundle to the 3-hour bundle. The outcome measures include hospital
mortality, hospital length of stay, ventilator-free days, and incidence of respiratory failure. The effectiveness of a clinical
intervention (Hour-1 bundle) is implemented using a rigorous implementation strategy (the Exploration,
adoption/Preparation, Implementation, Sustainment – EPIS – multi-level conceptual model) for both the 1- and 3-Hour
bundles. We will also evaluate a possible precision-based approach in this study. Routine clinical information available at
hospital presentation will identify 4 discrete, sepsis phenotypes and we hypothesize that 2 of these identify patients who
are significantly more likely to benefit from the 1-Hour bundle in future studies. Our team has extensive experience
conducting multi-center trials in sepsis guided by effective models of im...

## Key facts

- **NIH application ID:** 10871876
- **Project number:** 5R01HL162954-03
- **Recipient organization:** RHODE ISLAND HOSPITAL
- **Principal Investigator:** Mitchell M Levy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $687,161
- **Award type:** 5
- **Project period:** 2022-07-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10871876

## Citation

> US National Institutes of Health, RePORTER application 10871876, Assessment of Implementation Methods in Sepsis and Respiratory Failure (5R01HL162954-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10871876. Licensed CC0.

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