Clinical trial NCT04478721: Temocillin vs Meropenem for the Targeted Treatment of Bacteraemia Resistant to Third Gen Cephalosporins
Official title: Randomised Controlled Trial of Temocillin vs Meropenem for the Targeted Treatment of Bacteraemia Due to Enterobacteriaceae Showing Resistance to Third Generation Cephalosporins
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Bacteremia
Keywords: Bacteraemia
Enterobacteriaceae
Temocillin
Third-generation cephalosporin-resistant Enterobacteriaceae.
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
Collaborators: name: Spanish Network for Research in Infectious Diseases
name: Spanish Clinical Research Network - SCReN
First posted: 2020-07-21
Enrollment: 334
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized 1.1 to temocillin: meropenem
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with a "success" at the test of cure (TOC)
timeFrame: Up to 7-10 days after the last day of antibiotic therapy
measure: Survival at day 28
timeFrame: At day 28.
measure: Number of patients who do not need to stop or change the assigned drug
timeFrame: Up to 7-14 days after the last day of antibiotic therapy
measure: Number of patients who do not need to prolong therapy beyond 14 days
timeFrame: Up to 7-14 days after the last day of antibiotic therapy
measure: Not recurrence until day 28
timeFrame: At day 28.
Secondary outcomes:
measure: 28-day mortality
timeFrame: Up to day 28.
measure: Length of hospital stay (days)
timeFrame: Through study completion, an average of 28 days
measure: Length of intravenous therapy (days)
timeFrame: From day 1 of intravenous antibiotic treatment administration to last intravenous administration, average 14 days
measure: Length of total administration of therapy (days)
timeFrame: From day 1 of intravenous or oral antibiotic treatment administration to last intravenous or oral administration, average 14 days
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Up to day 28
measure: Number of subjects with resistance development during therapy
timeFrame: Up to day 28
measure: Recurrence rate
timeFrame: Up to day 28.
measure: Changes in Sequential Organ failure (SOFA) score
timeFrame: At days 1, 3, end of treatment (days 7-14) and visit 4
measure: Changes in Barthel Index for Activities of Daily Living (ADL) for patients older than 70 years old
timeFrame: At days 1, 3, end of treatment (days 7-14) and visit 4
Other outcomes:
measure: Peak Plasma Concentration (Cmax) of temocillin
timeFrame: At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3
measure: Minimum Plasma Concentration (Cmin) of temocillin
timeFrame: At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3
measure: Area under the plasma concentration versus time curve (AUC) of temocillin
timeFrame: At 1hour, 4hours, 6hours and y 8hours from temocillin first infusion, on days 1 and 3
Locations:
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago
state: A Coruña
city: Sabadell
country: Spain
facility: Hospital ParcTaulí
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Universitario Mútua Terrassa
state: Barcelona
city: Barakaldo
country: Spain
facility: Hospital Universitario de Cruces
state: Bizkaia
city: Santander
country: Spain
facility: Hospital Marqués de Valdecilla
state: Cantabria
city: Jerez de la Frontera
country: Spain
facility: Hospital Universitario de Jerez de la Frontera
state: Cádiz
city: Puerto Real
country: Spain
facility: Hospital Universitario de Puerto Real
state: Cádiz
city: Autol
country: Spain
facility: Complejo Hospitalario San Millán-San Pedro De La Rioja
state: La Rioja
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario La Coruña
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Almería
country: Spain
facility: Hospital Universitario Torrecárdenas
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Sant Pau
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Granada
country: Spain
facility: Hospital Universitario Clínico San Cecilio
city: Huelva
country: Spain
facility: Hospital Universitario Juan Ramón Jiménez
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaén
city: Lugo
country: Spain
facility: Hospital Universitario Locus Augusti, Lugo
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Murcia
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
city: Málaga
country: Spain
facility: Hospital Regional de Málaga
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Palma
country: Spain
facility: Hospital Universitari Son Espases
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme
city: Vigo
country: Spain
facility: Complejo Hospitalario Universitario de Vigo
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
Study officials:
affiliation: Hospital Universitario Virgen Macarena
name: Jesús Rodriguez Baño
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.