Temocillin vs Meropenem for the Targeted Treatment of Bacteraemia Resistant to Third Gen Cephalosporins
- Registration Number
- NCT04478721
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 334
- 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.
- <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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Temocillin Temocillin Patients enrolled in this arm, will receive 2g each 8 hours of intravenous temocillin. Meropenem Meropenem Patients enrolled in this arm, will receive 1g each 8 hours of intravenous meropenem.
- Primary Outcome Measures
Name Time Method Number of participants with a "success" at the test of cure (TOC) 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
Survival at day 28 At day 28. Number of patients who are alive
Number of patients who do not need to prolong therapy beyond 14 days Up to 7-14 days after the last day of antibiotic therapy Assigned treatment to be administered for less than 14 days
Not recurrence until day 28 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.Number of patients who do not need to stop or change the assigned drug 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.
- Secondary Outcome Measures
Name Time Method Length of hospital stay (days) Through study completion, an average of 28 days Number of days patients has been in-hospital
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 Up to day 28 Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Length of intravenous therapy (days) 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
Changes in Sequential Organ failure (SOFA) score At days 1, 3, end of treatment (days 7-14) and visit 4 Sequential Organ failure (SOFA) score changes
Changes in Barthel Index for Activities of Daily Living (ADL) for patients older than 70 years old 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
28-day mortality Up to day 28. Number of patients dead up to day 28.
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 days patients has been under intravenous or oral antibiotic treatment
Number of subjects with resistance development during therapy Up to day 28 Resistance development will be measured in a positive blood culture
Recurrence rate Up to day 28. Percentage of subjects with recurrence
Trial Locations
- Locations (34)
Hospital Universitario de Cruces
🇪🇸Barakaldo, Bizkaia, Spain
Hospital Clínico Universitario de Santiago
🇪🇸Santiago de Compostela, A Coruña, Spain
Hospital ParcTaulí
🇪🇸Sabadell, Barcelona, Spain
Hospital Universitario Mútua Terrassa
🇪🇸Terrassa, Barcelona, Spain
Hospital Universitario de Jerez de la Frontera
🇪🇸Jerez de la Frontera, Cádiz, Spain
Hospital Marqués de Valdecilla
🇪🇸Santander, Cantabria, Spain
Complejo Hospitalario San Millán-San Pedro De La Rioja
🇪🇸Autol, La Rioja, Spain
Hospital Universitario de Puerto Real
🇪🇸Puerto Real, Cádiz, Spain
Complejo Hospitalario de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Clínic de Barcelona
🇪🇸Barcelona, Spain
Complejo Hospitalario Universitario La Coruña
🇪🇸A Coruña, Spain
Hospital Universitario Torrecárdenas
🇪🇸Almería, Spain
Hospital Universitario Virgen de las Nieves
🇪🇸Granada, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Hospital Universitario Clínico San Cecilio
🇪🇸Granada, Spain
Hospital Universitario Reina Sofía
🇪🇸Córdoba, Spain
Hospital Sant Pau
🇪🇸Barcelona, Spain
Complejo Hospitalario de Jaén
🇪🇸Jaén, Spain
Hospital Universitario Juan Ramón Jiménez
🇪🇸Huelva, Spain
Hospital Universitario Locus Augusti, Lugo
🇪🇸Lugo, Spain
Hospital Universitario de la Princesa
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Clínico Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Hospital Regional de Málaga
🇪🇸Málaga, Spain
Hospital Universitari Son Espases
🇪🇸Palma, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Complejo Hospitalario Universitario de Vigo
🇪🇸Vigo, Spain
Hospital Universitario Virgen de Valme
🇪🇸Sevilla, Spain
Hospital Clínico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain