Bacteremia
Conditions
Keywords
Bacteraemia, Enterobacteriaceae, Temocillin, Third-generation cephalosporin-resistant Enterobacteriaceae.
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.
Interventions
DRUGTemocillin
The intervention of experimental arm will be Intravenous administration of temocillin.
DRUGMeropenem
The intervention of comparator arm will be intravenous administration of meropenem.
Sponsors
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Spanish Network for Research in Infectious Diseases
Spanish Clinical Research Network - SCReN
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized 1.1 to temocillin: meropenem
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 28-day mortality | Up to day 28. | Number of patients dead up to day 28. |
| Length of hospital stay (days) | Through study completion, an average of 28 days | Number of days patients has been in-hospital |
| 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 |
| 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 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 |
| 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 |
| 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 |
| Number of subjects with development of superimposed infections. | Up to day 28. | Development of superimposed infections will be measured in a positive culture |
Countries
Spain
Contacts
PRINCIPAL_INVESTIGATORJesús Rodriguez Baño
Hospital Universitario Virgen Macarena
Outcome results
None listed