| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| -Hospitalized patient with complicated UTI due to ESBL producing enterobacteriaceae (pyelonephritis, prostatitis or renal abscess) requiring parenteral antimicrobial therapy. |
| NA |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10054088 |
| E.1.2 | Term | Urinary tract infection bacterial |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective is to assess non-inferiority of temocillin compared with a carbapenem (meropenem, imipenem/cilastin, or ertapenem) as initial intravenous treatment based on the difference in composite cure rates (clinical and microbiological cure), five-seven days after the end of antibiotic therapy. Duration of antibiotic therapy will be decided according to current French guidelines. |
| NA |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives include:
"The comparison of the efficacy of the two strategies on :
oMicrobiological eradication and clinical cure separately, 5-7 days after the end of antibiotic therapy
oEarly microbiological eradication (3-4 days after randomization).
oFrequency of oral antibiotic switch
oLength of hospital stay.
oThe persistent cure rate (60 days after randomization).
oClinical recurrences (relapse or reinfection).
oMortality up to 60 days after randomization.
"The study of temocillin pharmacokinetic parameters in patients treated for ESBL-producing enterobacteriaceae related urinary tract infections.
"The impact of both drugs on intestinal colonization by multidrug-resistant (MDR) Gram negative bacilli (GNB) or temocillin-resistant Gram negative bacilli.
"The impact of both drugs on emergence of enterobacteriaceae strains resistant to temocillin or carbapenem
"The evaluation of the safety.
|
| NA |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Adult (> or = 18 years)
- Hospitalized patient with clinically significant monomicrobial UTI (*)
- Complicated UTI (**) due to ESBL producing enterobacteriaceae (pyelonephritis, prostatitis or renal abscess) requiring parenteral antimicrobial therapy
- Susceptibility (***) to temocillin and carbapenem as evidenced by testing results
- For woman able to procreate: negative pregnancy test in fertile women and use of an effective method of contraception (abstinence, oral contraceptives, intra-uterine device, diaphragm with spermicide and condom). All forms of hormonal contraception are acceptable
- Signed informed consent
- Patient affiliated to the social security system
(*) UTI was defined according the SPILF guidelines [20] as pyuria (white blood cell count greater than 104/mL in urine) associated with clinical symptoms of urinary tract infection.
(**) Only complicated urinary tract infections (Pyelonephritis, prostatitis and renal abcess) will be included. Cystitis will be excluded.
Bacteriuria was defined as a bacterial culture > 103 UFC/mL.
(***) Susceptibility to temocillin and carbapenems will be determined according to CA-SFM 2015 guidelines.
|
| NA |
|
| E.4 | Principal exclusion criteria |
- Patient infected with a bacteria which is not an ESBL-producing enterobacteriacae.
- Patient infected with a strain resistant to temocillin.
- Polymicrobial infection.
- Hypersensitivity and/or previous intolerance to carbapenem or temocillin or penicillins or any other beta-lactam.
- Patient presenting another site of infection than urinary (except onset of bacteraemia from urinary tract origin due to Gram negative bacteria).
- Woman who is pregnant, breastfeeding, or expecting to conceive at any time during the study (pregnancy test will be conducted for woman without menopause).
- Palliative care of life expectance < 90 days.
- Ongoing empirical treatment of the urinary tract infections with carbapenem.
- Delay in randomization > 24 hours after identification of ESBL producing enterobacteriacaeae in urinary and/or blood culture.
- Participation in other clinical trial for the infection.
- Patient under tutorship or curatorship.
- Patient unable to give consent.
|
| NA |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary assessment criterion:
Composite cure: the primary endpoint was defined as achieving both clinical cure and microbiological eradication of all baseline pathogens 5-7 days after completion of treatment.
- Clinical cure is defined as complete resolution, substantial improvement (i.e. reduction in severity of all baseline signs and symptoms and lack of worsening), or return to pre-infections signs and symptoms of complicated lower urinary tract infections or pyelonephritis without the need for additional antibiotic therapy.
- The microbiological efficacy (i.e. eradication) will be assessed by quantitative urine culture and defined as follows < 103 CFU/mL of the baseline pathogen.
Secondary assessments criteria:
- Microbiological eradication and clinical cure separately, 5-7 days after the end of antibiotic therapy
- Early microbiological eradication (3-4 days after randomization)
- Oral antibiotic switch
- Length of hospital stay defined as the time from randomization to hospital discharge
- Persistent cure rate (60 days after randomization) was defined as a sustained clinical cure.
- Clinical recurrences (relapse or reinfection).
- Mortality up to 60 days after randomization. Death for any reason or for infectious events
- Pharmacokinetic of temocillin according to kidney function.
- Microbiota impact of study treatment bacilli (Time frame: screening, 5-7 days after treatment completion).
- MIC and resistance: Emergence of enterobacteriaceae strains resistant to temocillin or carbapenem (Time frame: Day 5-7 after end of treatment (test of cure) until day 60 of follow-up).
- Safety of intravenous antibiotic administration in this indication (Time frame: to the last visit, at a 60 ± 5 days after randomization (from the first day of study drugs administration)).
|
| NA |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Microbiological eradication and clinical cure separately, 5-7 days after the end of antibiotic therapy
- Early microbiological eradication (3-4 days after randomization)
- Oral antibiotic switch
- Length of hospital stay defined as the time from randomization to hospital discharge
- Persistent cure rate (60 days after randomization) was defined as a sustained clinical cure.
- Clinical recurrences (relapse or reinfection).
- Mortality up to 60 days after randomization. Death for any reason or for infectious events
- Pharmacokinetic of temocillin according to kidney function.
- Microbiota impact of study treatment bacilli (Time frame: screening, 5-7 days after treatment completion).
- MIC and resistance: Emergence of enterobacteriaceae strains resistant to temocillin or carbapenem (Time frame: Day 5-7 after end of treatment (test of cure) until day 60 of follow-up).
- Safety of intravenous antibiotic administration in this indication (Time frame: to the last visit, at a 60 ± 5 days after randomization (from the first day of study drugs administration)).
|
| NA |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Traitements de référence : carbapénèmes |
| Carbapenem |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
Print
