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

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: Completed
• Conditions: Bacteremia
• Intervention / Treatment: Drug: Temocillin; Drug: Meropenem

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 (Actual): 334
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario La Coruna
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante
  • Almería, Spain, 04009
    • Hospital Universitario Torrecárdenas
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08041
    • Hospital Sant Pau
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofía
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves
  • Granada, Spain, 18016
    • Hospital Universitario Clínico San Cecilio
  • Huelva, Spain, 21005
    • Hospital Universitario Juan Ramon Jimenez
  • Lugo, Spain, 27003
    • Hospital Universitario Locus Augusti, Lugo
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Murcia, Spain, 30120
    • Hospital Clínico Universitario Virgen de la Arrixaca
  • Málaga, Spain, 29010
    • Hospital Regional de Malaga
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Palma, Spain, 07120
    • Hospital Universitari Son Espases
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Seville, Spain, 41014
    • Hospital Universitario Virgen de Valme
  • Vigo, Spain, 36313
    • Complejo Hospitalario Universitario de Vigo
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Hospital ParcTaulí
    • Terrassa, Barcelona, Spain, 08221
      • Hospital Universitario Mútua Terrassa
  • Bizkaia
    • Barakaldo, Bizkaia, Spain, 48903
      • Hospital Universitario de Cruces
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Marques de Valdecilla
  • Cádiz
    • Jerez de la Frontera, Cádiz, Spain, 11407
      • Hospital Universitario de Jerez de la Frontera
    • Puerto Real, Cádiz, Spain, 11510
      • Hospital Universitario de Puerto Real
  • La Rioja
    • Logroño, La Rioja, Spain, 26560
      • Complejo Hospitalario San Millán-San Pedro De La Rioja
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Complejo Hospitalario de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 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).

Patients with polymicrobial bacteremia caused by more than one Enterobacteriaceae species may also be included, provided at least one of them is resistant to third-generation cephalosporins, and both are susceptible to meropenem and temocillin.

• Duration of intravenous treatment is planned to be at least 4 days from randomization, or 3 days if the empirical treatment prior to randomization was active.
• The patient signed informed consent form.
• Potentially fertile patients must have a negative pregnancy test.

Exclusion Criteria:

• <18 years
• Pregnancy
• Breastfeeding
• Terminal condition, with life expectancy of less than 30 days, or palliative care , such that no actions will be taken to control the source of infection if necessary. Patients receiving palliative care with a life expectancy greater than 30 days may be included if source control is not necessary or, if necessary, will be carried out.
• Allergy to betalactams
• Polymicrobial bacteraemia (except when the other microorganism is considered a contaminant, (e.g. coagulase-negative staphylococci or diphtheroids in a single blood culture, or in cases where more than one Enterobacteriaceae species is isolated, provided that at least one isolate is resistant to third-generation cephalosporins and both are susceptible to meropenem and temocillin).
• Infections typically needing prolonged >14 days of therapy (e.g., endocarditis, prosthetic joint infection, vascular graft infection, empyema, chronic prostatitis) or meningitis. Patients who initially do not have a confirmed diagnosis of these infections may be included; if the diagnosis is made subsequently, the patient may be kept in the trial at the discretion of the investigator, establishing the duration of treatment that he considers necessary.
• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

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)	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	Number of patients who are alive	At day 28.
Number of patients who do not need to stop or change the assigned drug	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	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	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	Number of patients dead up to day 28.	Up to day 28.
Length of hospital stay (days)	Number of days patients has been in-hospital	Through study completion, an average of 28 days
Length of intravenous therapy (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)	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	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	Resistance development will be measured in a positive blood culture	Up to day 28
Recurrence rate	Percentage of subjects with recurrence	Up to day 28.
Changes in Sequential Organ failure (SOFA) score	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	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
Number of subjects with development of superimposed infections.	Development of superimposed infections will be measured in a positive culture	Up to day 28.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax) of temocillin	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	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	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

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Collaborators: Spanish Clinical Research Network - SCReN; Spanish Network for Research in Infectious Diseases
• Investigators: Principal Investigator: Jesús Rodriguez Baño, Hospital Universitario Virgen Macarena

Publications and helpful links

General Publications

• Marin-Candon A, Rosso-Fernandez CM, Bustos de Godoy N, Lopez-Cerero L, Gutierrez-Gutierrez B, Lopez-Cortes LE, Barrera Pulido L, Borreguero Borreguero I, Leon MJ, Merino V, Camean-Fernandez M, Retamar P, Salamanca E, Pascual A, Rodriguez-Bano J; ASTARTE Study Group. Temocillin versus meropenem for the targeted treatment of bacteraemia due to third-generation cephalosporin-resistant Enterobacterales (ASTARTE): protocol for a randomised, pragmatic trial. BMJ Open. 2021 Sep 27;11(9):e049481. doi: 10.1136/bmjopen-2021-049481.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2020
• Primary Completion (Actual): December 26, 2024
• Study Completion (Actual): December 26, 2024

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): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Enterobacteriaceae; Temocillin; Bacteraemia; Third-generation cephalosporin-resistant Enterobacteriaceae.
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Pathological Conditions, Signs and Symptoms; Bacteremia; Toxemia; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amides; beta-Lactams; Lactams; Carbapenems; Thienamycins; Meropenem; temocillin
• 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