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

Bacteremia Clinical Trial

— ASTARTÉ  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04478721
• Other study ID #: ASTARTÉ
• Secondary ID: 2020-000064-39
• Status: Recruiting
• Phase: Phase 3
• Start date: December 15, 2020
• Est. completion date: September 2023

Study information

• Verified date: May 2023
• Source: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Contact: Clara Rosso
• Phone: +34955013414
• Email: claram.rosso[@]juntadeandalucia.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 334
• Est. completion date: September 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bacteremia

Intervention

Drug:
• Temocillin
The intervention of experimental arm will be Intravenous administration of temocillin.
• Meropenem
The intervention of comparator arm will be intravenous administration of meropenem.

Locations

Country	Name	City	State
Spain	Complejo Hospitalario Universitario La Coruña	A Coruña
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Universitario Torrecárdenas	Almería
Spain	Complejo Hospitalario San Millán-San Pedro De La Rioja	Autol	La Rioja
Spain	Hospital Universitario de Cruces	Barakaldo	Bizkaia
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Sant Pau	Barcelona
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Hospital Universitario Clínico San Cecilio	Granada
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Hospital Universitario Juan Ramón Jiménez	Huelva
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	Hospital Universitario de Jerez de la Frontera	Jerez de la Frontera	Cádiz
Spain	Hospital Universitario Locus Augusti, Lugo	Lugo
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario de la Princesa	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Regional de Málaga	Málaga
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Clínico Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital Universitari Son Espases	Palma
Spain	Complejo Hospitalario de Navarra	Pamplona	Navarra
Spain	Hospital Universitario de Puerto Real	Puerto Real	Cádiz
Spain	Hospital ParcTaulí	Sabadell	Barcelona
Spain	Hospital Marqués de Valdecilla	Santander	Cantabria
Spain	Hospital Clínico Universitario de Santiago	Santiago de Compostela	A Coruña
Spain	Hospital Universitario Virgen de Valme	Sevilla
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Universitario Mútua Terrassa	Terrassa	Barcelona
Spain	Complejo Hospitalario Universitario de Vigo	Vigo
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza

Sponsors (3)

Lead Sponsor	Collaborator
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla	SCReN Spanish research Network- CTU-HUVR, Spanish Network for Research in Infectious Diseases

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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
Primary	Survival at day 28	Number of patients who are alive	At day 28.
Primary	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
Primary	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
Primary	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	28-day mortality	Number of patients dead up to day 28.	Up to day 28.
Secondary	Length of hospital stay (days)	Number of days patients has been in-hospital	Through study completion, an average of 28 days
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of subjects with resistance development during therapy	Resistance development will be measured in a positive blood culture	Up to day 28
Secondary	Recurrence rate	Percentage of subjects with recurrence	Up to day 28.
Secondary	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
Secondary	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