FQ Restriction for the Prevention of CDI (FIRST)

Fluoroquinolone Restriction Ofr the Prevention of C. Difficile Infection (CDI)_the FIRST Trial

This study evaluates the effectiveness of a new intervention, fluoroquinolone (FQ) Preprescription Authorization (PPA) strategy, to reduce and prevent Clostridium difficile infection (CDI) in hospital intensive care units (ICUs). The investigators will model a successful FQ PPA strategy in several Wisconsin ICUs and compare whether the intervention has improved outcomes in reducing CDIs. An additional goal of the study is to evaluate environmental and work system factors using systems engineering models in order to determine the most successful way to implement these new strategies.

Study Overview

• Status: Enrolling by invitation
• Conditions: Clostridium Difficile Infection; Clostridium Difficile; C Difficile Colitis
• Intervention / Treatment: Other: fluoroquinolone preprescription authorization; Other: Control

Detailed Description

The objective of the proposed study is to evaluate the effectiveness and implementation of a fluoroquinolone (FQ) Preprescription Authorization (PPA) as an antibiotic stewardship (AS) strategy to target and prevent CDI, promote appropriate antibiotic use, and reduce the transmission of resistant bacteria. This will contribute to the long-term goal of reducing the burden of Clostridium difficile infection (CDI), which is an essential step in improving the safety and quality of healthcare. FQ PPA is a particularly promising AS strategy to reduce CDI. Although FQs are one of the most frequently utilized classes of antibiotics in inpatient acute care facilities and are closely associated with risk for CDI, FQ usage has not been the focus of control efforts in endemic settings in the US. The proposed study will use an effectiveness-implementation hybrid type 2 design to simultaneously evaluate the efficacy of an FQ PPA intervention to reduce CDI as well as the key considerations for implementing such an intervention successfully. Intensive care units in acute care hospitals throughout Wisconsin will participate in this stepped wedge cluster randomized controlled trial. The specific aims for the proposed study are to: 1) determine the impact of a FQ PPA on hospital-onset and healthcare-associated CDI rates and other clinical outcomes compared with usual care; and 2) evaluate the implementation of FQ PPA using a systems engineering approach. For aim 1, electronic health record data will be used to evaluate the impact of the FQ PPA on hospital-onset and healthcare-associated CDI, as well as other important clinical outcomes. For aim 2, surveys and interviews with healthcare providers will be used to evaluate the contextual, implementation, and work system factors that contribute to successful implementation of a FQ PPA intervention. In addition to addressing an urgent need to identify effective AS strategies, this study will provide a framework to implement and evaluate other interventions for healthcare-acquired infection (HAI) prevention. Regardless of the results, the proposed study will generate data, tools and methods with widespread applicability for AS initiatives in healthcare-associated infection prevention.

• Study Type: Observational
• Enrollment (Estimated): 11000

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo-Arizona
  • California
    • Moreno Valley, California, United States, 92555
      • Riverside University Health System Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo-Rochester
  • Missouri
    • Kansas City, Missouri, United States, 64112
      • St. Luke's Health System
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch at Galveston
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Health Systems
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin Hospital & Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study population is comprised of clinicians and patients at 12 ICUs in 5 acute care hospitals. Once initiated, the intervention will be applied to all patients admitted to the ICU and all healthcare workers involved in antibiotic prescribing in that ICU.

Description

Inclusion Criteria:

• Medical-surgical intensive care unit with at least 10 beds
• Presence of existing antibiotic stewardship (AS) program with pharmacist and ID physician support
• Electronic health record (EHR) vendor is Epic Systems Corporation
• Has ability to extract antibiotic usage data (days of therapy)
• Has ability to extract required outcomes data (CDI, mortality, length of ICU stay)
• Ability to extract or abstract data on indications for antibiotic use
• Adherence to best practices for infection control relevant to CDI

Exclusion Criteria:

• Medical-surgical intensive care units with a FQ restriction in place as part of their usual care procedures will be excluded.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
FQ PPA Group; Fluoroquinolone Preprescription Authorization from Infection Control consult, once, prior to prescribing fluoroquinolone	Other: fluoroquinolone preprescription authorization; Requires authorization from Infection Control consult prior to prescribing fluoroquinolone; Other Names: FQ PPA
Control Group; No preprescription authorization needed from Infection control prior to prescribing fluoroquinolone	Other: Control; Does not require authorization from Infection Control prior to prescribing fluoroquinolone; Other Names: No FQ PPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the incidence of healthcare facility-onset Clostridiodes difficile infection (HO-CDI) with intensive care unit (ICU)-onset before and after initiating FQ PPA intervention	Effectiveness of fluoroquinolone (FQ) Pre-prescription Authorization (PPA) intervention to reduce HO-CDI with ICU-onset will be assessed by comparing changes in incidence over pre- and post-intervention periods.	24 Months
Change in the overall incidence of HO-CDI before and after initiating FQ PPA intervention	Effectiveness of FQ PPA intervention to reduce HO-CDI will be assessed by calculating changes in incidence over pre- and post-FQ PPA intervention periods.	24 months
Change in incidence of healthcare-associated CDI (HA-CDI) before and after initiation of FQ PPA intervention	Effectiveness of FQ PPA intervention to reduce HA-CDI will be assessed by calculating changes in incidence over pre- and post-FQ PPA intervention periods.	24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the usage of FQ from the time of participant hospital admission per 1000 patient-days.	To confirm fidelity of implementation of FQ PPA intervention, the change in the usage of FQ and other antibiotics in days of therapy per 1000 patient-days will be measured.	24 months
Change in usage of non-FQ antibiotics per patient admission, and days of therapy per 1000 PD	To confirm fidelity of implementation of FQ PPA intervention, the change in the usage of antibiotics other than FQ in days of therapy per 1000 patient-days will be measured.	24 months
Change in the number of patients per site showing Acute Kidney Injury (AKI) using the Kidney Disease Improving Global Outcomes (KDIGO) guideline definition.	The potential of this intervention to increase usage of alternative antibiotics with a negative clinical outcomes such as AKI, as compared with usual care, will be measured by assessing change in incidence of AKI, defined as: Increase in serum creatinine by ≥ 0.3 mg/dl within 48 hours, or increase in serum creatinine to ≤1.5 times baseline or urine volume <0.5 mg/kg/hour for 6 hours.	24 months
Hospital Mortality Rate of Participants	Hospital mortality	24 months
Length of Participants's Hospital Stay	The impact of FQ PPA on negative clinical outcomes as compared with usual care by the length of hospital stay	24 months
Number of Participants Readmitted within 30 Days	The impact of FQ PPA intervention compared with usual care as it impacts the number of patients readmitted within 30 days.	24 months
Number of Incidences of Hospital Acquired Infections	The impact of FQ PPA on negative clinical outcomes as compared with usual care by the incidence of other, non-CDI hospital acquired infections.	24 months
Baseline proportion of CDI due to NAP-1 in site ICUs and associated facilities.	This would reflect whether the FQ PPA intervention was impacted by the prevalence of the strain of CDI most susceptible to FQ antibiotics.	24 months

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Agency for Healthcare Research and Quality (AHRQ)
• Investigators: Principal Investigator: Nasia Safdar, MD PhD, University of Wisconsin, Madison

Publications and helpful links

General Publications

• Safdar N, Parmasad V, Brown R, Carayon P, Lepak A, O'Horo JC, Schulz L. Decreasing ICU-associated Clostridioides difficile infection through fluoroquinolone restriction, the FIRST trial: a study protocol. BMJ Open. 2021 Jun 29;11(6):e046480. doi: 10.1136/bmjopen-2020-046480.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: October 2, 2018
• First Submitted That Met QC Criteria: February 18, 2019
• First Posted (Actual): February 21, 2019

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Clostridium Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Bacterial Agents; Fluoroquinolones
• Other Study ID Numbers: 2018-0852; A534265 (Other Identifier: UW, Madison); 1R01HS026226-01 (U.S. AHRQ Grant/Contract); SMPH/MEDICINE/MEDICINE*I (Other Identifier: UW, Madison); Protocol ver 5.0 20 Dec 2020 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No