Temocillin vs Meropenem for the Targeted Treatment of Bacteraemia Resistant to Third Gen Cephalosporins (ASTARTÉ)

May 2, 2023 updated by: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Randomised Controlled Trial of Temocillin vs Meropenem for the Targeted Treatment of Bacteraemia Due to Enterobacteriaceae Showing Resistance to Third Generation Cephalosporins

A Phase 3, Multicenter, Randomised, Controlled, Open-Label Study to demonstrate noninferiority of temocillin (unauthorized investigational medicinal product IMP in Spain, but authorized in Belgium and UK) vs a carbapenem antibiotic (meropenem) in adults with bacteraemia due to third-generation cephalosporin-resistant Enterobacteriaceae.

The duration of treatment will be between 7 and 14 days. From the 5th day of intravenous treatment, the sequential oral treatment is permitted if the patient meets appropriate conditions.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The objective of the trial is to demonstrate the non-inferiority of temocillin (2g each 8 hours, intravenous) to carbapenems (meropenem 1g each 8 hours, intravenous) in terms of efficacy and safety in the targeted treatment of bacteraemia due to Enterobacteriaceae resistant to third-generation cephalosporins, and therefore provide evidence for the use of temocillin in these infections.

The duration of treatment will be between 7 and 14 days. From the 5th day of intravenous treatment, the sequential oral treatment is permitted if the patient meets appropriate conditions.

Study Type

Interventional

Enrollment (Anticipated)

334

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Spain
      • A Coruña, Spain, 15006
        • Recruiting
        • Complejo Hospitalario Universitario La Coruna
        • Contact:
        • Principal Investigator:
          • Dolores Sousa Regueiro, Clínico
      • Alicante, Spain, 03010
        • Recruiting
        • Hospital General Universitario de Alicante
        • Contact:
        • Principal Investigator:
          • Esperanza Merino de Lucas, Clínico
      • Almería, Spain, 04009
        • Recruiting
        • Hospital Universitario Torrecárdenas
        • Contact:
        • Principal Investigator:
          • M. Ángeles Esteban Moreno, Clínico
      • Barcelona, Spain, 08003
        • Recruiting
        • Hospital del Mar
        • Contact:
        • Principal Investigator:
          • Juan Pablo Horcajada Gallego, Clínico
      • Barcelona, Spain, 08036
        • Active, not recruiting
        • Hospital Clinic de Barcelona
      • Barcelona, Spain, 08041
        • Recruiting
        • Hospital Sant Pau
        • Contact:
        • Principal Investigator:
          • Joaquín López-Contreras González, Clínico
      • Córdoba, Spain, 14004
        • Recruiting
        • Hospital Universitario Reina Sofia
        • Contact:
        • Principal Investigator:
          • Ángela Cano Yuste, Clínico
      • Granada, Spain, 18014
        • Recruiting
        • Hospital Universitario Virgen de las Nieves
        • Contact:
        • Principal Investigator:
          • Miguel Ángel López, Clínico
      • Granada, Spain, 18016
        • Recruiting
        • Hospital Universitario Clínico San Cecilio
        • Contact:
        • Principal Investigator:
          • Andrés Ruiz Sancho, Clínico
      • Huelva, Spain, 21005
        • Recruiting
        • Hospital Universitario Juan Ramon Jimenez
        • Contact:
        • Principal Investigator:
          • Francisco Javier Martínez Marcos, Clínico
      • Jaén, Spain, 23007
        • Active, not recruiting
        • Complejo Hospitalario de Jaén
      • Lugo, Spain, 27003
        • Recruiting
        • Hospital Universitario Locus Augusti, Lugo
        • Contact:
        • Principal Investigator:
          • Mª José García País, Clínico
      • Madrid, Spain, 28034
        • Recruiting
        • Hospital Universitario Ramón y Cajal
        • Contact:
        • Principal Investigator:
          • Rosa Escudero, Clínico
      • Madrid, Spain, 28007
        • Recruiting
        • Hospital General Universitario Gregorio Marañón
        • Contact:
        • Principal Investigator:
          • María Olmedo Samperio, Clínico
      • Madrid, Spain, 28006
        • Recruiting
        • Hospital Universitario de La Princesa
        • Contact:
        • Principal Investigator:
          • Ana Barrios Blandino, Clínico
      • Madrid, Spain, 28046
        • Withdrawn
        • Hospital Universitario La Paz
      • Murcia, Spain, 30120
        • Recruiting
        • Hospital Clínico Universitario Virgen de la Arrixaca
        • Contact:
        • Principal Investigator:
          • Elisa García Vázquez, Clínico
      • Málaga, Spain, 29010
        • Recruiting
        • Hospital Universitario Virgen de La Victoria
        • Principal Investigator:
          • Enrique Nuño Álvarez, Clínico
      • Málaga, Spain, 29010
        • Recruiting
        • Hospital Regional De Malaga
        • Principal Investigator:
          • Lucía Valiente de Santis, Clínico
      • Palma, Spain, 07120
        • Recruiting
        • Hospital Universitari Son Espases
        • Contact:
        • Principal Investigator:
          • María Peñaranda Vera, Clínico
      • Sevilla, Spain, 41009
        • Recruiting
        • Hospital Universitario Virgen Macarena
        • Contact:
        • Principal Investigator:
          • Jesús Rodríguez Baño, Clínico
      • Sevilla, Spain, 41013
        • Recruiting
        • Hospital Universitario Virgen del Rocío
        • Contact:
        • Principal Investigator:
          • Manuel Enrique Jiménez Mejías, Clínico
      • Sevilla, Spain, 41014
        • Recruiting
        • Hospital Universitario Virgen de Valme
        • Contact:
        • Principal Investigator:
          • Juan Corzo Delgado, Clínico
      • Vigo, Spain, 36313
        • Recruiting
        • Complejo Hospitalario Universitario de Vigo
        • Contact:
        • Principal Investigator:
          • María Teresa Pérez Rodríguez, Clínico
      • Zaragoza, Spain, 50009
        • Withdrawn
        • Hospital Clinico Universitario Lozano Blesa
    • A Coruña
      • Santiago de Compostela, A Coruña, Spain, 15706
        • Withdrawn
        • Hospital Clinico Universitario de Santiago
    • Barcelona
      • Sabadell, Barcelona, Spain, 08208
        • Recruiting
        • Hospital ParcTaulí
        • Contact:
        • Principal Investigator:
          • Oriol Gasch Blasi, Clínico
      • Terrassa, Barcelona, Spain, 08221
        • Recruiting
        • Hospital Universitario Mutua Terrassa
        • Contact:
        • Principal Investigator:
          • Esther Calbo Sebastián, Clínico
    • Bizkaia
      • Barakaldo, Bizkaia, Spain, 48903
        • Active, not recruiting
        • Hospital Universitario de Cruces
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Recruiting
        • Hospital Marques de Valdecilla
        • Contact:
        • Principal Investigator:
          • M. Carmen Fariñas Álvarez, Clínico
    • Cádiz
      • Jerez de la Frontera, Cádiz, Spain, 11407
        • Recruiting
        • Hospital Universitario de Jerez de la Frontera
        • Principal Investigator:
          • Salvador López Cárdenas, Clínico
      • Puerto Real, Cádiz, Spain, 11510
        • Recruiting
        • Hospital Universitario de Puerto Real
        • Principal Investigator:
          • Alberto Romero Palacios, Clínico
    • La Rioja
      • Autol, La Rioja, Spain, 26560
        • Recruiting
        • Complejo Hospitalario San Millán-San Pedro De La Rioja
        • Contact:
        • Principal Investigator:
          • José Antonio Oteo Revuelta, Clínico
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Recruiting
        • Complejo Hospitalario de Navarra
        • Contact:
        • Principal Investigator:
          • José Ramón Yuste Ara, Clínico

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult patients with monomicrobial bacteremia due to Enterobacteriaceae showing resistance to cefotaxime, ceftriaxone (MIC >2 mg/L) and/or ceftazidime (MIC >4 mg/L), and sensible to temocillin (MIC ≤8 mg/L, except in bacteremia only of urinary origin, for which the criterion is MIC ≤16 mg/L ) and meropenem (MIC ≤2 mg/L).
  • Duration of intravenous treatment is planned to be at least 4 days.
  • The patient signed informed consent form.

Exclusion Criteria:

  • <18 years
  • Pregnancy
  • Breastfeeding
  • Palliative care
  • Allergy to betalactams
  • Polymicrobial bacteraemia
  • Infections typically needing prolonged >14 days of therapy (e.g., endocarditis, prosthetic joint infection, vascular graft infection, empyema, chronic prostatitis) or meningitis
  • Active empirical treatment> 96 hours after initial blood culture extraction
  • Delay in inclusion> 48 h
  • Recruited in another clinical trial with active treatment
  • Peritoneal dialysis or continuous hemofiltration
  • extreme gravity or imminent death

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Temocillin
Patients enrolled in this arm, will receive 2g each 8 hours of intravenous temocillin.
Drug: Temocillin
The intervention of experimental arm will be Intravenous administration of temocillin.
Active Comparator: Meropenem
Patients enrolled in this arm, will receive 1g each 8 hours of intravenous meropenem.
Drug: Meropenem
The intervention of comparator arm will be intravenous administration of meropenem.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with a "success" at the test of cure (TOC)
Time Frame: Up to 7-10 days after the last day of antibiotic therapy
A success at the test of cure is the resolution of infection symptoms
Up to 7-10 days after the last day of antibiotic therapy
Survival at day 28
Time Frame: At day 28.
Number of patients who are alive
At day 28.
Number of patients who do not need to stop or change the assigned drug
Time Frame: Up to 7-14 days after the last day of antibiotic therapy

Reasons for not change can be no adverse event, no perceived failure during treatment or no occurrence of a superimposed infection.

Participants who stop or change the assigned drug will not meet the primary outcome.
Up to 7-14 days after the last day of antibiotic therapy
Number of patients who do not need to prolong therapy beyond 14 days
Time Frame: Up to 7-14 days after the last day of antibiotic therapy
Assigned treatment to be administered for less than 14 days
Up to 7-14 days after the last day of antibiotic therapy
Not recurrence until day 28
Time Frame: At day 28.

Recurrence is reappearance of symptoms with positive blood culture for the same microorganism.

Participants with recurrence will not meet the primary outcome.
At day 28.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
28-day mortality
Time Frame: Up to day 28.
Number of patients dead up to day 28.
Up to day 28.
Length of hospital stay (days)
Time Frame: Through study completion, an average of 28 days
Number of days patients has been in-hospital
Through study completion, an average of 28 days
Length of intravenous therapy (days)
Time Frame: From day 1 of intravenous antibiotic treatment administration to last intravenous administration, average 14 days
Number of days patients has been under intravenous antibiotic treatment
From day 1 of intravenous antibiotic treatment administration to last intravenous administration, average 14 days
Length of total administration of therapy (days)
Time Frame: From day 1 of intravenous or oral antibiotic treatment administration to last intravenous or oral administration, average 14 days
Number of days patients has been under intravenous or oral antibiotic treatment
From day 1 of intravenous or oral antibiotic treatment administration to last intravenous or oral administration, average 14 days
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: Up to day 28
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Up to day 28
Number of subjects with resistance development during therapy
Time Frame: Up to day 28
Resistance development will be measured in a positive blood culture
Up to day 28
Recurrence rate
Time Frame: Up to day 28.
Percentage of subjects with recurrence
Up to day 28.
Changes in Sequential Organ failure (SOFA) score
Time Frame: At days 1, 3, end of treatment (days 7-14) and visit 4
Sequential Organ failure (SOFA) score changes
At days 1, 3, end of treatment (days 7-14) and visit 4
Changes in Barthel Index for Activities of Daily Living (ADL) for patients older than 70 years old
Time Frame: At days 1, 3, end of treatment (days 7-14) and visit 4
Barthel Index for Activities of Daily Living (ADL) score changes; score from 0, completely dependent patient to 100, completely independent for activities of daily living
At days 1, 3, end of treatment (days 7-14) and visit 4

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak Plasma Concentration (Cmax) of temocillin
Time Frame: At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3
Exploratory objective in a reduced number of patients on which plasma levels of temocillin will be measured to determine maximum plasma levels of temocillin
At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3
Minimum Plasma Concentration (Cmin) of temocillin
Time Frame: At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3
Exploratory objective in a reduced number of patients on which plasma levels of temocillin will be measured to determine minimum plasma levels of temocillin
At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3
Area under the plasma concentration versus time curve (AUC) of temocillin
Time Frame: At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3
Exploratory objective in a reduced number of patients on which plasma levels of temocillin will be measured to determine area under curve of temocillin
At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Collaborators

Spanish Network for Research in Infectious Diseases
SCReN Spanish research Network- CTU-HUVR

Investigators

  • Principal Investigator: Jesús Rodriguez Baño, Hospital Universitario Virgen Macarena

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 15, 2020

Primary Completion (Anticipated)

September 1, 2023

Study Completion (Anticipated)

September 1, 2023

Study Registration Dates

First Submitted

March 23, 2020

First Submitted That Met QC Criteria

July 15, 2020

First Posted (Actual)

July 21, 2020

Study Record Updates

Last Update Posted (Actual)

May 3, 2023

Last Update Submitted That Met QC Criteria

May 2, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ASTARTÉ
  • 2020-000064-39 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Planning for the study will be shared with potential sites pertaining to Spanish Network for Research in Infectious Disease (REIPI)for participation. IPD is not foreseen out of this groups due to the specific characteristics of patients and sites to be candidates for study participation.

IPD Sharing Time Frame

From starting to three years of study completion planification

IPD Sharing Access Criteria

Spanish Network for Research in Infectious Disease investigators

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Bacteremia

Clinical Trials on Temocillin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Armenia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe