Cefiderocol vs Best Available Therapy for Carbapenem-resistant Acinetobacter Baumannii-calcoaceticus Complex Infections: A Target Trial Emulation

This study aims to compare 28-day mortality among patients with carbapenem resistant A. baumannii infections in two hypothetical target trials where patients receive 7 days of a cefiderocol-based treatment strategy or 7 days of a best available therapy treatment strategy.

Study Overview

• Status: Active, not recruiting
• Conditions: Antimicrobial Drug Resistance; Acinetobacter Baumannii Infection; Carbapenem Resistant Bacterial Infection

Detailed Description

please see uploaded study protocol

• Study Type: Observational
• Enrollment (Estimated): 5000

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Hospitalized adult patients with a clinical culture positive for carbapenem resistant A. baumannii and received an antibiotic with possible in vitro activity against carbapenem resistant A. baumannii in the time frame of interest (i.e., days before culture collection until 2 days after first available antibiotic susceptibility test result was made available) and admitted to US hospitals reporting to the PINC-AI healthcare database between 2018-2024 will be eligible for inclusion in the hypothetical target trials.

Description

Inclusion Criteria:

• Hospitalized adults (≥ 18 years of age)
• Carbapenem resistant A. baumannii-calcoaceticus complex clinical culture
• Antimicrobial agent with possible in vitro activity against carbapenem resistant A. baumannii-calcoaceticus complex initiated in the time frame of 2 days before culture collection until 2 days following first available antibiotic susceptibility test result being made available

Exclusion Criteria:

• Patients with no antibiotic susceptibility testing
• Patients with only A. baumannii infection diagnosed by rapid diagnostic tests (i.e., multiplex polymerase chain reaction)
• Initiation of antimicrobial agent outside of selected time frame (i.e., 2 days before culture collection until 2 days after first available antibiotic susceptibility test result was made available)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Reciept of cefiderocol; Inpatients with carbapenem-resistant Acinetobacter baumannii infection that receive empiric and/or targeted therapy including cefiderocol.
Reciept of best available therapy (BAT); Inpatients with carbapenem-resistant Acinetobacter baumannii infection that receive empiric and/or targeted therapy with activity against the infection but does not include cefiderocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	In hospital mortality or discharge to hospice during the hospital stay	During inpatient admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Stay	Duration of hospitalization among surviving patients	Inpatient admission
Recurrent CRAB Infection	clinical culture positive for carbapenem-resistant A. baumannii (CRAB) infection within the same encounter downstream of the index episode and within 30 days.	Within 30 days post discharge
Development of antibiotic resistance to initial antibiotic treatment	Development of antibiotic resistance on a subsequent positive clinical culture to an antibiotic administered during prior infectious episode	Subsequent admissions

Collaborators and Investigators

• Sponsor: National Institutes of Health Clinical Center (CC)
• Investigators: Principal Investigator: Sameer Kadri, MD, National Institutes of Health CC

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 5, 2025
• First Submitted That Met QC Criteria: November 7, 2025
• First Posted (Actual): November 10, 2025

Study Record Updates

• Last Update Posted (Actual): November 10, 2025
• Last Update Submitted That Met QC Criteria: November 7, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Cefiderocol; Target trial emulation; Carbapenem-resistant Acinetobacter baumannii
• Other Study ID Numbers: BD070725

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Aggregate data, analytic methods, and data dictionary will be shared upon request to the primary contact.

Drug and device information, study documents

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