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

NCT04478721 | Completed Phase 3 DMC

• 2 other identifiers: ASTARTÉ2020-000064-39
• Study Type: interventional
• Target: 334
• Locations: 1 country
• Sites: 29

Brief Summary

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.

Conditions

Bacteremia

Keywords

Bacteraemia; Enterobacteriaceae; Temocillin; Third-generation cephalosporin-resistant Enterobacteriaceae.

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (10)

• 28-day mortality

  Up to day 28.

• Length of hospital stay (days)

  Through study completion, an average of 28 days

• Length of intravenous therapy (days)

  From day 1 of intravenous antibiotic treatment administration to last intravenous administration, average 14 days

• Length of total administration of therapy (days)

  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

  Up to day 28

Other Outcomes (3)

• Peak Plasma Concentration (Cmax) of temocillin

  At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3

• Minimum Plasma Concentration (Cmin) 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

  At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3

Study Arms (2)

Temocillin

EXPERIMENTAL

Patients enrolled in this arm, will receive 2g each 8 hours of intravenous temocillin.

Drug: Temocillin

Meropenem

ACTIVE COMPARATOR

Patients enrolled in this arm, will receive 1g each 8 hours of intravenous meropenem.

Drug: Meropenem

Interventions

Temocillin DRUG

The intervention of experimental arm will be Intravenous administration of temocillin.

Temocillin

Meropenem DRUG

The intervention of comparator arm will be intravenous administration of meropenem.

Meropenem

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \<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
• Recruited in another clinical trial with active treatment
• Peritoneal dialysis or continuous hemofiltration

Sponsors & Collaborators

• Fundación Pública Andaluza para la gestión de la Investigación en Sevilla: lead
• Spanish Network for Research in Infectious Diseases: collaborator
• Spanish Clinical Research Network - SCReN: collaborator

Study Sites (29)

Hospital ParcTaulí

Sabadell, Barcelona, 08208, Spain

Location

Hospital Universitario Mútua Terrassa

Terrassa, Barcelona, 08221, Spain

Location

Hospital Universitario de Cruces

Barakaldo, Bizkaia, 48903, Spain

Location

Hospital Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario de Jerez de la Frontera

Jerez de la Frontera, Cádiz, 11407, Spain

Location

Hospital Universitario de Puerto Real

Puerto Real, Cádiz, 11510, Spain

Location

Complejo Hospitalario San Millán-San Pedro De La Rioja

Logroño, La Rioja, 26560, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Complejo Hospitalario Universitario La Coruña

A Coruña, 15006, Spain

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Hospital Universitario Torrecárdenas

Almería, 04009, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

Location

Hospital Universitario Clínico San Cecilio

Granada, 18016, Spain

Location

Hospital Universitario Juan Ramón Jiménez

Huelva, 21005, Spain

Location

Hospital Universitario Locus Augusti, Lugo

Lugo, 27003, Spain

Location

Hospital Universitario de la Princesa

Madrid, 28006, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Regional de Málaga

Málaga, 29010, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

Location

Hospital Universitari Son Espases

Palma, 07120, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitario Virgen de Valme

Seville, 41014, Spain

Location

Complejo Hospitalario Universitario de Vigo

Vigo, 36313, Spain

Location

Related Publications (1)

• 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.

  PMID: 34580096 DERIVED

MeSH Terms

Conditions

Bacteremia; Toxemia

Interventions

temocillin; Meropenem

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jesús Rodriguez Baño

  Hospital Universitario Virgen Macarena

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized 1.1 to temocillin: meropenem

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: July 21, 2020
• Study Start: December 15, 2020
• Primary Completion: December 26, 2024
• Study Completion: December 26, 2024
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: From starting to three years of study completion planification
• Access Criteria: Spanish Network for Research in Infectious Disease investigators

Locations

ES (29)