Resumen

Estudio multicéntrico, aleatorizado, doble ciego, de no inferioridad de la combinación de cefepime 2 g/AAI101 500 mg en comparación con piperacilina 4 g/tazobactam 500 mg en una población de pacientes adultos con infección complicada del tracto urinario (ITUc) o pielonefritis aguda (PA). El estudio se llevará a cabo en aproximadamente 115 centros ubicados en la Unión Europea, Estados Unidos, América Central, América del Sur y Sudáfrica.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Male or female patients \>18 years of age at the time of signing of informed consent;
Expectation that the patient's cUTI or AP will require hospitalisation and initial treatment with at least 7 days of intravenous (i.v.) antibiotics;
Female patients who are no longer of childbearing potential
Female patients of childbearing potential must have a negative urine and/or serum pregnancy test (serum β-human chorionic gonadotropin) within 1 day prior to study entry;
Male patients, female patients receiving hormone replacement therapy (HRT), and female patients of childbearing potential must agree to use highly effective contraception methods
Pyuria, defined as: a. White blood cell count \>10 cells/mm3 in unspun urine or ≥10 cells/high power field in spun urine sediment; or b. Urinalysis/dipstick analysis positive for leukocyte esterase;
Clinical signs and/or symptoms of cUTI or AP
Have a baseline urine culture specimen obtained within 48 hours prior to randomization
Expectation, in the judgment of the Investigator, that any implanted urinary instrumentation (e.g., nephrostomy tubes, ureteric stents, etc.) will be surgically removed or replaced before or within 24 hours after randomisation, unless removal or replacement is considered unsafe or contraindicated.

Criterios de exclusión

Known urine culture with Gram-positive primary pathogen at ≥105 colony-forming units (CFU)/mL (not contaminant) or suspected Gram-positive pathogen by Gram staining (Note: Gram staining is optional);
History of significant hypersensitivity or allergic reaction to cefepime, piperacillin/tazobactam, any of the excipients used in the respective formulations, any beta-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, or monobactams), or any beta-lactamase inhibitors (e.g., tazobactam, sulbactam, or clavulanic acid);
In the opinion of the Investigator, the patient is considered unlikely to survive the approximately 6-week study period;
Weight \>180 kg;
Concurrent infection that would interfere with evaluation of response to the study antibiotics;
Need for or receipt of concomitant systemic antimicrobial agents after signing of informed consent, in addition to those designated in the study-treatment groups, with the exception of a single oral dose of any antifungal treatment for vaginal candidiasis;
Receipt of potentially effective systemic antibacterial therapy for a continuous duration of \> 24 hours during the previous 72 hours before the study-qualifying baseline urine is obtained;
Complicated urinary tract infection (UTI) known at study entry to be caused by pathogens resistant to the study antibiotics;
Likely to require the use of an antibiotic for cUTI or AP prophylaxis during the patient's participation in the study;
Intractable UTI at baseline that the Investigator anticipates would require \>14 days of study drug therapy;
Complete, permanent obstruction of the urinary tract that is not anticipated to be medically or surgically relieved during i.v. study therapy and before End of Treatment (EOT);
Gross hematuria requiring intervention other than administration of study drug or removal or exchange of a urinary catheter;
Presence of any known or suspected disease or condition that, in the opinion of the Investigator, may confound the assessment of efficacy.
Suspected or confirmed acute bacterial prostatitis, orchitis, epididymitis, or chronic bacterial prostatitis as determined by history and/or physical examination;
Impairment of renal function with estimated glomerular filtration rate \<30 mL/min/1.73 m2 calculated by the 4-variable Modification of Diet in Renal Disease study equation,
Urinary tract surgery within 7 days prior to randomisation or urinary tract surgery planned during the study period (except surgery required to relieve an obstruction or place a stent or nephrostomy prior to EOT);
Any condition or circumstance that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of study data;
Any rapidly progressing disease or immediately life-threatening illness, including acute hepatic failure and respiratory failure;
Presence of sepsis, producing life-threatening organ dysfunction
A QT interval corrected using Fridericia's formula \>450 msec;
Immunocompromising condition, including known history of acquired immune deficiency syndrome or known recent CD4 count \<200/mm3, hematological malignancy, or bone marrow transplantation; or immunosuppressive therapy including cancer chemotherapy, medications for prevention of organ transplantation rejection, or the administration of corticosteroids ≥20 mg of prednisone or equivalent per day administered continuously for \>14 days prior to randomisation;
One or more of the following laboratory abnormalities in baseline specimens obtained at Screening: aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, or total bilirubin level \>3 × upper limit of normal, or current clinically significant liver disease, including any form of known liver cirrhosis;
One or more of the following laboratory abnormalities at Screening: platelet count \<50,000/μL, absolute neutrophil count \<1,000/mm3, or hemoglobin \<8 g/dL;

Estudio de fase 3, aleatorizado, doble ciego, para evaluar la eficacia y seguridad de cefepime-AAI101 en comparación con piperacilina/tazobactam en el tratamiento de infecciones complicadas del tracto urinario, incluyendo pielonefritis aguda.

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

cefepime/AAI101 combination

Piperacillin/tazobactam

Ubicaciones

HIGA Dr Ramon Carrillo

Patrocinadores