Antibiotic Stewardship Strategy for Sepsis

(REVAMP Trial)

Recruiting at 5 trial locations

Overseen By Kai Inoki, MPH

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Children's Hospital of Philadelphia

Disqualifiers: Volunteers, Limited English proficiency

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

52500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new strategy can reduce vancomycin use, a common antibiotic, in children with suspected sepsis in Pediatric Intensive Care Units (PICUs). The trial includes creating guidelines for antibiotic use, providing feedback to doctors, and educating them on its application. Medical records of patients in PICUs with suspected sepsis will be reviewed to guide the intervention. Children admitted to one of the participating PICUs during the study period can participate. As an unphased trial, this study offers a unique opportunity to improve antibiotic use in critical care settings for children.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

What prior data suggests that this multifaceted de-implementation strategy is safe for PICU patients and clinicians?

Research has shown that programs focusing on the wise use of antibiotics, like the one being studied, are generally safe. These programs aim to prevent unnecessary side effects from antibiotics. For instance, studies indicate that such strategies can reduce harmful effects like toxic reactions. By ensuring correct antibiotic use, they also help improve patient health and reduce the risk of serious infections, such as Clostridium difficile, which can cause severe diarrhea. Although not a medication, this program aims to make antibiotic use safer and more effective. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to optimize how antibiotics are used for treating sepsis in pediatric intensive care units (PICUs). Unlike standard treatments that focus solely on administering antibiotics, this strategy incorporates a comprehensive approach. It involves providing PICU clinicians with clinical guidelines, feedback, and education about Vancomycin use, which could lead to more informed decision-making. By reducing unnecessary antibiotic use, this strategy could help combat antibiotic resistance and improve patient outcomes in the long run.

What evidence suggests that this multifaceted de-implementation strategy is effective for reducing vancomycin use in sepsis?

This trial will implement a multifaceted strategy to reduce unnecessary antibiotic use in PICU settings. Research has shown that a well-rounded plan can effectively decrease antibiotic use. In one study, a hospital reduced its antibiotic use by 14.6% after implementing such a plan. Another study found that ICU infections caused by drug-resistant bacteria decreased from 57.7% to 48.8%. These findings suggest that specific guidelines and education can lower unnecessary antibiotic use and resistance. The goal is to use antibiotics only when necessary, reducing harmful effects and improving treatment outcomes. ^{3 6 7 8 9}

Who Is on the Research Team?

Kathleen Chiotos

Principal Investigator

children's hospital of philadelphia

Are You a Good Fit for This Trial?

This trial is for pediatric patients admitted to participating Pediatric Intensive Care Units (PICUs) during the study period. It aims to see if a new strategy can reduce unnecessary use of vancomycin, an antibiotic that treats serious infections.

Inclusion Criteria

Patient admitted to one of the participating PICUs during the study period

Employed by one of the participating sites

PICU prescribing clinician (including attending physicians, fellows, residents, nurse practitioners, and physician assistants) OR sepsis stakeholder (leader of sepsis quality improvement work, medical director) at one of the participating sites at the time the survey is deployed

Exclusion Criteria

N/A

Volunteers or other non-employee hospital staff

Limited English proficiency

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Data Collection

Retrospective quantification of unit-level vancomycin use over 24 months using EHR data

24 months

Intervention

Implementation of a multifaceted stewardship intervention to reduce vancomycin use, including clinical guidelines, education, and feedback

24 months

Ongoing site visits and virtual meetings

Follow-up

Participants are monitored for safety and effectiveness after intervention

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Multifaceted de-implementation strategy

Trial Overview The study tests a de-implementation strategy including clinical guidelines on proper vancomycin use, feedback on its usage rates in PICUs, and clinician education. The goal is to lower overuse without compromising patient care.

How Is the Trial Designed?

Group I: PICU Clinicians and Sepsis stakeholders Experimental Treatment 1 Intervention

Clinicians and sepsis stakeholders in the participating sites will be primarily recruited via email. During the course of this multifaceted intervention: * All the PICU (Pediatric Intensive Care Unit) prescribing clinicians and sepsis stakeholders in the participating sites will receive clinical guidelines, unit-level feedback reports, and education on Vancomycin use during the intervention. * Investigators will perform semi-structured interviews with 90 PICU clinicians and sepsis stakeholders. * Surveys will be sent to all eligible clinicians, estimated to be up to 2500 individuals across the 4 sites. These structured surveys will be done at baseline and at 9 months post-implementation.

Group II: PICU Patients with suspected sepsis Active Control 1 Intervention

Research procedures involving patients will be limited to medical record review. This medical record review will help inform the intervention directed at PICU clinicians/stakeholders and the assessment of study outcomes. Approximately 50,000 patients will participate in the study. Data elements will be collected at each site and stored as password-protected Comma-separated values (CSV) files. These files will not contain any direct Protected Health Information (PHI) but will contain elements of date (e.g., date of admission, date of suspected sepsis episode). The study Identification (ID) number will be used to identify each unique patient. Each site will collect and store data in compliance with the Children's Hospital of Philadelphia (CHOP) and local Institutional Review Board (IRB) policies.

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

Children's Healthcare of Atlanta

Collaborator

Trials

172

Recruited

108,000+

St. Louis Children's Hospital

Collaborator

Trials

30

Recruited

83,200+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Centers for Disease Control and Prevention

Collaborator

Trials

902

Recruited

25,020,000+

Published Research Related to This Trial

Prompt initiation of antibiotic therapy is crucial for critically ill patients with sepsis and septic shock, as it can significantly improve outcomes.

Antibiotic stewardship programs are essential to balance the need for effective treatment with the risk of developing multidrug-resistant infections, emphasizing the importance of optimizing treatment duration and de-escalation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How Antibiotics Stewardship Can Be Safely Implemented in Patients with Septic Shock? de Montmollin, E., Timsit, JF.[2022]

The decline in antibiotic development is a critical issue, particularly in ICUs facing multidrug-resistant infections, which are becoming more common in healthcare settings.

Implementing antibiotic stewardship guidelines, as promoted by the Surviving Sepsis Campaign, is essential for optimizing antibiotic use in critically ill patients to improve outcomes and reduce resistance, especially by ensuring appropriate initial therapy and adjusting based on pathogen susceptibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria. Bassetti, M., De Waele, JJ., Eggimann, P., et al.[2020]

Accurate diagnosis and prompt administration of appropriate antibiotics are crucial for improving mortality rates in sepsis and septic shock, highlighting the importance of timely medical intervention.

Effective antimicrobial stewardship, which includes selecting the right empirical antibiotics and considering de-escalation strategies, can enhance patient outcomes while minimizing the risks of toxicity and antibiotic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial Therapy and Antimicrobial Stewardship in Sepsis. Seok, H., Jeon, JH., Park, DW.[2020]

In a study of 191 critically ill patients with enterococcal bacteremia, those with vancomycin-resistant Enterococcus (VRE) had a significantly higher 28-day mortality rate compared to those with vancomycin-sensitive Enterococcus (VSE), with a relative risk of nearly 2.0.

Delayed administration of appropriate antibiotics (more than 3 days after diagnosis) in patients with VRE bacteremia was linked to increased mortality, highlighting the need for faster detection and treatment strategies to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic Stewardship Related to Delayed Diagnosis and Poor Prognosis of Critically Ill Patients with Vancomycin-Resistant Enterococcal Bacteremia: A Retrospective Cohort Study. Yang, MC., Wu, YK., Lan, CC., et al.[2022]

The implementation of an antimicrobial stewardship program (ASP) at a Veterans Affairs hospital significantly reduced 30-day mortality rates in patients prescribed vancomycin, with mortality dropping from 64.3% pre-stewardship to 35.7% during stewardship.

Key factors associated with increased mortality included older age, nephrotoxicity, hypotension, and admission to the intensive care unit, highlighting the importance of careful monitoring and management in these high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased mortality in patients prescribed vancomycin after implementation of antimicrobial stewardship program. Conway, EL., Sellick, JA., Horey, A., et al.[2022]

The antimicrobial stewardship program (ASP) involving a multidisciplinary team significantly reduced hospital stay, readmission, and mortality rates among 1340 hospitalized patients, indicating improved clinical outcomes.

The intervention also led to a decrease in the use of reserve antibiotics and a better balance in intravenous to oral antibiotic use, showcasing the effectiveness of clinical pharmacists in optimizing antibiotic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Multidisciplinary Team Escalating Approach on Antibiotic Stewardship in the United Arab Emirates. Sadeq, AA., Shamseddine, JM., Babiker, ZOE., et al.[2021]

Sepsis, particularly from community-acquired infections, has a high mortality rate exceeding 25%, with lung infections being the most common cause.

Immediate broad-spectrum antibiotic therapy is crucial for treating severe sepsis, but it must be balanced with strategies to prevent antibiotic overuse and resistance, utilizing biomarkers like procalcitonin to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial antimicrobial management of sepsis. Niederman, MS., Baron, RM., Bouadma, L., et al.[2021]

Effective antimicrobial stewardship in sepsis management can improve clinical outcomes and reduce costs by minimizing adverse effects and the risk of antibiotic resistance.

Implementing strategies such as guideline-based empirical therapy, de-escalation of treatment, and therapeutic drug monitoring can significantly enhance patient safety and treatment efficacy in sepsis care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stewardship in sepsis. Del Pozo, JL.[2020]

Critically ill patients with sepsis or septic shock face a higher risk of death, making early and aggressive treatment crucial for improving outcomes.

Challenges in managing antimicrobials include timely selection, physiological changes affecting drug effectiveness, and variability in patient responses; using rapid diagnostics and therapeutic drug monitoring can help tailor treatments more effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing Pharmacokinetics-Pharmacodynamics of Antimicrobial Management in Patients with Sepsis: A Review. Phe, K., Heil, EL., Tam, VH.[2021]

Citations

1. withpower.com withpower.com/trial/phase-sepsis-7-2023-93e19

Antibiotic Stewardship Strategy for Sepsis (REVAMP Trial) The Antibiotic Stewardship Strategy for Sepsis aims to use antibiotics effectively while minimizing harmful effects like toxic reactions and antibiotic ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7760905/

Effectiveness and Acceptance of Multimodal Antibiotic ... Overall, antibiotic use was significantly decreased by 14.6% in the whole hospital after ASP implementation (336 daily dose of antibiotics per ...

3. nature.com nature.com/articles/s41598-022-07915-9

A multifaceted educational intervention improved anti ... A cluster-randomized controlled trial on an educational intervention did not show improvements of sepsis management or outcome.

4. mdpi.com mdpi.com/2077-0383/11/15/4409

Effectiveness of a Multifaced Antibiotic Stewardship Program The proportion of multi-drug-resistant bacteria (MDR) in ICU-acquired infections fell from 57.7% to 48.8%. ICU mortality and length of stay remained unchanged, ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1198743X23006286

Assessment of implementation strategies adopted for ... Implementation outcomes are akin to clinical outcomes; they are geared towards assessing the effectiveness of an implementation process or strategy [24]. A ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7113444/

Antimicrobial Therapy and Antimicrobial Stewardship in Sepsis The goal of antimicrobial stewardship is to promote appropriate use of antibiotics and to reduce antibiotic exposure.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5449351/

The impact of a multifaceted intervention including sepsis ... Our data show significant improvement in outcomes even with modest increase in the compliance with the CVP and ScvO2 elements, supporting the ...

8. esmed.org esmed.org/stewardships-role-in-sepsis-management-key-insights/

Stewardship's Role in Sepsis Management: Key Insights Combining antimicrobial stewardship with diagnostic stewardship enhances sepsis management by improving recognition, treatment, and outcomes. Key factors ...

9. academic.oup.com academic.oup.com/cid/article/62/10/e51/2462846

Implementing an Antibiotic Stewardship Program: Guidelines ... The benefits of antibiotic stewardship include improved patient outcomes, reduced adverse events including Clostridium difficile infection (CDI), improvement in ...