Complicated Urinary Tract Infections caused by a Gram-negative Pathogen
Conditions
Interventions
Cefiderocol Group:Cefiderocol, 2.0g iv gtt ,Q8h, 7~14Days .
Control Group:Imipemide/Cilastatin, 1.0g iv gtt ,Q8h, 7~14Day
Sponsors
Huashan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Hospitalized patients, =18 years at the time of signing informed consent, who have provided written informed consent or their informed consent was provided by legal guardian. (If the subject is incapable of civil conduct, the written informed consent of his/her guardian shall be obtained; if the subject is a person with limited civil conduct, the written informed consent of him/herself and his/her guardian shall be obtained, when the guardian agrees on behalf of the subject. If a subject is unable to read or if his/her guardian is unable to read, an impartial witness should be present during the entire informed consent discussion). 2. Has a clinical diagnosis of either cUTI with pyelonephritis or cUTI without pyelonephritis: cUTI with a history of at least one of the following: • Indwelling urinary catheter or recent instrumentation of the urinary tract (within 14 days prior to screening) • Urinary retention caused by benign prostatic hypertrophy • Urinary retention of at least 100 milliliters (mL) or more of residual urine after voiding (neurogenic bladder) • Obstructive uropathy (nephrolithiasis, fibrosis, etc.) • Azotemia caused by intrinsic renal disease (blood urea nitrogen [BUN] and creatinine values greater than normal laboratory values) OR Pyelonephritis and normal urinary tract anatomy, i.e., acute uncomplicated pyelonephritis. AND All patients must have at least two of the following signs or symptoms: • Chills or rigors or warmth associated with fever (oral or tympanic temperature greater than or equal to 38 degrees Celsius) • Flank pain (pyelonephritis) or suprapubic/pelvic pain (cUTI) • Nausea or vomiting • Dysuria, urinary frequency, or urinary urgency • Costo-vertebral angle tenderness on physical examination AND Urinalysis evidence of pyuria demonstrated by: • Dipstick analysis positive for leukocyte esterase • Or =10 WBCs per µL in unspun urine, or =10 WBCs per high power field in spun urine) 3. Patients who had a positive urine culture from urine sample collected within 48 hours prior to randomization containing =10 5 CFU/mL of a Gram-negative uropathogen known or likely to be susceptible to Imipenem (IPM) and Cefiderocol are eligible for this study. Note: patients may be randomized and start Cefiderocol/control treatment prior to the results of the urine culture being available. For the patients who had received prior therapeutic antibacterial drug therapy (=24 hours during 72 hours before randomization), cultures obtained prior to antibacterial therapy for cUTI will be considered the baseline culture. Positive isolates considered pathogens will be sent to the central laboratory, if available. 4. Patients, who have been treated previously with an empiric antibiotic other than the study medications, but failed treatment, both clinically and microbiologically, are eligible for the study if they have an identified uropathogen which is non-susceptible to the empiric treatment and is a Gram-negative uropathogen known or likely to be susceptible to both IPM (or other alternative carbapenem antibiotic) and Cefiderocol. 5. Subjects receiving antibiotic prophylaxis for urinary tract infection (UTI) who present with signs and symptoms consistent with an active new UTI may be enrolled provided all other eligibility criteria are met including obtaining a pre-treatment qualifying baseline urine culture. 6. Female patients can participate if they are surgically sterile by hysterectomy and/or bilateral oophorectomy with appropriat
Exclusion criteria
Exclusion criteria: 1. Urine specimen identifies only a Gram-positive pathogen (not contaminant) suspected by Gram-staining or identified a Gram-negative uropathogen resistant to IPM or Cefiderocol. Note: if both a Gram-positive and a Gram-negative uropathogens are identified, the patient should be given a concomitant antibiotic which has only Gram-positive activity, e.g., vancomycin, daptomycin, linezolid. Resistance to IPM is based on the minimum inhibitory concentration (MIC) or zone diameter breakpoints which are different depending on the genus/species of the identified pathogen. Resistance to IPM should be based on local laboratory determination. In the case of a Gram-negative uropathogen resistant to IPM or Cefiderocol, the investigator could continue the patient on study treatment based on his/her assessment that the patient’s clinical condition has improved. 2. Patient’s urine culture at baseline isolates >2 uropathogens, regardless of colony count, or patient has a confirmed fungal UTI. 3. Patients with asymptomatic bacteriuria, the presence of =10 5 CFU/mL of a uropathogen and pyuria but without local or systemic symptoms. 4. Patient is receiving hemodialysis or peritoneal dialysis. Impairment of renal function including an estimated CrCl 24 hours of therapeutic antibacterial drug therapy during 72 hours before randomization. Note: Patients may receive =24 hours of a therapeutic antibacterial drug therapy during 72 hours before randomization. Patients who have objective documentation of clinical progression of cUTI while on antibacterial drug therapy, or patients who received antibacterial drugs for prophylaxis and then develop cUTI, may be appropriate for enrollment. 14. Patients who have received another investigational drug or device within 30 days prior to randomization. 15. Patients who have previously received Cefiderocol. 16. Patients with any condition or circumstance that, in the opinion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The percentage of subjects with composite response of microbiological eradication and clinical response at TOC; | — |
Secondary
| Measure | Time frame |
|---|---|
| The percentage of subjects with composite response of microbiological eradication and clinical response at EA, EOT, and FUP;The percentage of subjects with microbiological eradication at TOC, EA, EOT, and FUP;The percentage of subjects with microbiological eradication per uropathogen at TOC, EA, EOT, and FUP;The percentage of subjects with clinical response at TOC, EA, EOT, and FUP;The percentage of subjects with clinical response per uropathogen at TOC, EA, EOT, and FUP;Subgroup analysis of cUTI patients with bacteremia: the percentages of subjects with composite response, microbiological eradication, and clinical response at TOC, EA, EOT, and FUP;Safety assessments included physical examinations, clinical laboratory values (hematology, blood chemistry, and urinalysis), vital signs, 12-lead ECG, and AEs; | — |
Countries
China
Contacts
Public ContactZhang Yingyuan / Huang Haihui
Huashan Hospital, Fudan University
Outcome results
None listed