Use of Cefiderocol in the Management of Gram-Negative Infections (PERSEUS)

Retrospective Analysis of Real-World Use of Cefiderocol in the Management of Gram-Negative Infections as Part of the Early Access Program (PERSEUS Study)

The aim of this study is to describe the use of cefiderocol in the management of Gram-negative infections (GNIs) in participants treated through the Early Access Program (EAP) in Spain.

Study Overview

• Status: Completed
• Conditions: Gram-Negative Infection
• Intervention / Treatment: Drug: Cefiderocol

Detailed Description

This is a multicenter, retrospective, chart review of existing medical records in participants who received cefiderocol for a GNI as part of the Shionogi EAP. Access to cefiderocol was granted as Medication not approved in Spain subject to RD 1015/2009, which dictates that each case is approved on an individual basis by the Spanish Agency of Medicines. This study will be conducted at Spanish sites where cefiderocol was supplied via the EAP, beginning in 2018.

• Study Type: Observational
• Enrollment (Actual): 314

Contacts and Locations

Study Locations

• Spain
  • A Coruña, Spain
    • Complejo Hospitalario Universitario A Coruña
  • Albacete, Spain
    • Complejo Hospitalario Universitario de Albacete
  • Alicante, Spain
    • Hospital Universitario San Juan de Alicante
  • Alicante, Spain
    • Hospital General Universitario de Alicante Doctor Balmis
  • Alicante, Spain
    • Hospital Universitario de Torrevieja
  • Alicante, Spain
    • Hospital Vega Baja de Orihuela
  • Almeria, Spain
    • Hospital Universitario Torrecardenas, Almeria
  • Badalona, Spain
    • Hospital Universitari Germans Trias i Pujol
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Hospital Universitari de Bellvitge
  • Barcelona, Spain
    • Hospital Clinic i Provincial de Barcelona
  • Bilbao, Spain
    • Hospital Universitario de Cruces
  • Burgos, Spain
    • Hospital Universitario de Burgos
  • Ciudad Real, Spain
    • Hospital General Universitario de Ciudad Real
  • Córdoba, Spain
    • Hospital Universitario Reina Sofia
  • Elche, Spain
    • Hospital General Universitario de Elche
  • Girona, Spain
    • Hospital Universitari de Girona Doctor Josep Trueta
  • Granada, Spain
    • Hospital Universitario Virgen de las Nieves
  • Guadalajara, Spain
    • Hospital Universitario de Guadalajara, Guadalajara
  • Jaen, Spain
    • Complejo Hospitalario de Jaén
  • Jerez de la Frontera, Spain
    • Hospital Universitario de Jerez
  • Las Palmas de Gran Canaria, Spain
    • Hospital Universitario de Gran Canaria Doctor Negrín
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Hospital Universitario Clínico San Carlos
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Hospital Universitario de la Princesa
  • Madrid, Spain
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain
    • Hospital Universitario Puerta de Hierro
  • Madrid, Spain
    • Hospital Universitario Infanta Leonor
  • Madrid, Spain
    • Hospital Universitario Infanta Sofía
  • Madrid, Spain
    • Hospital Universitario Fundacion Alcorcon
  • Madrid, Spain
    • Hospital Central de la Defensa Gomez Ulla
  • Madrid, Spain
    • Hospital Universitario Sureste, Arganda del Rey
  • Murcia, Spain
    • Hospital Clinico Universitario Virgen de la Arrixaca
  • Málaga, Spain
    • Hospital Regional Universitario de Malaga
  • Ourense, Spain
    • Complejo Hospitalario Universitario de Ourense
  • Palma de Mallorca, Spain
    • Hospital Universitari Son Espases
  • Palma de Mallorca, Spain
    • Quironsalud Palmaplanas
  • Pamplona, Spain
    • Complejo Hospitalario de Navarre
  • Pontevedra, Spain
    • Complejo Hospitalario de Pontevedra
  • Santa Cruz de Tenerife, Spain
    • Hospital Universitario de Canarias, La Laguna
  • Santa Cruz de Tenerife, Spain
    • Hospital Universitario Nuestra Señora Candelaria
  • Santander, Spain
    • Hospital Universitario Marqués de Valdecilla
  • Santiago, Spain
    • Complejo Hospitalario Universitario de Santiago
  • Sevilla, Spain
    • Hospital Universitario Virgen de la Macarena
  • Sevilla, Spain
    • Hospital Universitario Virgen de Valme
  • Sevilla, Spain
    • Hospital Público Comarcal de la Merced
  • Toledo, Spain
    • Hospital Virgen de la Salud
  • Valencia, Spain
    • Hospital Clínico Universitario de Valencia
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe
  • Vic, Spain
    • Hospital Universitari de Vic (Consorci Hospitalari de Vic)
  • Vigo, Spain
    • Hospital Alvaro Cunqueiro
  • Zaragoza, Spain
    • Hospital Clínico Universitario Lozano Blesa
  • Zaragoza, Spain
    • Hospital Univeritario Miguel Servet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Participants treated with cefiderocol for GNIs through the EAP in Spain.

Description

Inclusion Criteria:

• Have received first course of cefiderocol.
• Have received treatment for at least 72 hours (complete) with cefiderocol as a part of clinical compassionate management, requested in the EAP.

Exclusion Criteria:

• Enrolled in any clinical trial of an investigational product.
• Documented Acinetobacter spp infection.
• Incomplete medical records for the following essential data elements:
• Cefiderocol usage (dose, duration, frequency)
• Data to be able to determine clinical success (primary objective)
• Co-infection with a GNB resistant to cefiderocol in 28 days of the initial dose of cefiderocol.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cefiderocol Treated; Participants who have been treated with at least 72 hours of cefiderocol through the EAP in Spain.	Drug: Cefiderocol; Cefiderocol is a novel siderophore cephalosporin developed for the treatment of infections caused by Gram-negative bacteria (GNB), including those resistant to carbapenems.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate Of Clinical Success	The rate of clinical success will be reported as the percent clinical success of participants treated with cefiderocol for participants who receive at least 72 hours of cefiderocol through the EAP for the treatment of Gram-negative, carbapenem-resistant infections (except for Acinetobacter spp).	From Day 1 (cefiderocol initiation) through Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Resolution of Infection or Clinical Cure After Treatment With Cefiderocol		Day 1 (cefiderocol initiation), every 7 days up to Day 28
In-hospital Length of Stay	Length of stay in hospital (days) for participants with infections treated by cefiderocol will be reported.	Day 1 (cefiderocol initiation) up to Day 28, death, or discharge (whichever occurs first)
Length of Stay in Intensive Care Unit (ICU)	Length of stay in ICU (days) for participants with infections treated by cefiderocol will be reported.	Day 1 (cefiderocol initiation) up to Day 28, death, or discharge (whichever occurs first)
Length of Invasive Ventilation	Length of invasive ventilation (days) for participants with infections treated by cefiderocol will be reported.	Day 1 (cefiderocol initiation) up to Day 28, death, or discharge (whichever occurs first)
All-cause In-hospital Mortality	All-cause in-hospital mortality will be reported after cefiderocol initiation.	Day 14, Day 28
Cause of Death	The relation of death to the reference infection, as reported in the medical notes, will be reported.	Day 1 (cefiderocol initiation) through Day 28
Rate of Microbiological Eradication	The rate of eradication of carbapenem-resistant GNIs will be reported as the percent microbiological eradication among participants with blood stream infections (BSIs) and complicated urinary tract infections (cUTIs)/UTIs from 24 hours of cefiderocol initiation until Day 28. BSI microbiological eradication will be defined as the absence of a positive follow-up blood culture, in which the same organism as the initial blood culture was obtained. Any positive blood cultures drawn within 24 hours of the initial positive culture will be considered as the same episode. cUTI/UTI microbiological eradication will be defined as an absence of a positive follow-up culture of the same organism as the initial infection obtained.	Day 1 (24 hours post cefiderocol initiation) through Day 28
Severity of Illness	The severity of illness at the time of cefiderocol administration at baseline will be described by a Sequential Organ Failure Assessment (SOFA) Score, quickSOFA (qSOFA) score, level of organ support, and presence of septic shock. The SOFA score for participants in ICU or qSOFA score for participants outside ICU will be reported for days -3, 0, and 7 in relation to the date of cefiderocol initiation.	Day 1 (cefiderocol initiation) through Day 28
Number of Participants With Adverse Drug Reactions (ADRs)	The number of participants with serious and non-serious adverse events with explicit attribution to cefiderocol (ADR) will be reported.	Up to 28 days post-treatment completion with cefiderocol, death, or discharge (whichever occurs first)
Number of Participants Experiencing Resolution of Infection or Clinical Cure After Prolonged Treatment With Cefiderocol		Day 1 (cefiderocol initiation), every 10 days up to Day 60

Collaborators and Investigators

• Sponsor: Shionogi

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2022
• Primary Completion (Actual): June 16, 2023
• Study Completion (Actual): June 16, 2023

Study Registration Dates

• First Submitted: February 16, 2023
• First Submitted That Met QC Criteria: March 28, 2023
• First Posted (Actual): March 29, 2023

Study Record Updates

• Last Update Posted (Actual): June 26, 2023
• Last Update Submitted That Met QC Criteria: June 23, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Spain; Cefiderocol; Early Access Program
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: 2020-266-4

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No