Safety and Efficacy Study of Ftortiazinon in the Treatment of Patients With Complicated Urinary Tract Infections Caused by P. Aeruginosa

Inclusion Criteria:

• 1. The ability to understand the requirements of the study participants, to givewritten consent to participate in the study (including the use and transfer ofinformation about the patient's health related to the study) and the implementation ofthe procedures provided by the Study Protocol.

2. Availability of the patient's written consent to participate in the study accordingto the current legislation.
3. Male or female participants must be ≥18 and ≤80 years of age. 4. It is expectedthat patient's treatment of complicated UTI will require hospitalization and the useof antibiotic therapy.
4. Suspected or documented complicated UTI as defined below and subject to themandatory presence of one or more of the risks associated with the complicated UTIlisted below: Complicated urinary tract infection (complicated UTI):

• presence of at least 2 of the following signs or symptoms:

• chills, tremors, or body temperature increases associated with fever (body temperatureof 38ºC) (fever documented by a medical professional within 24 hours prior toscreening);
• nausea or vomiting within 24 hours prior to screening;
• dysuria, frequent urination or urgent need to urinate;
• pain in the lower abdomen;
• acute pain in the side (occurred within 7 days prior to randomization) or pain in theregion of the rib-vertebral angle during physical examination. • leukocyturia in a urine sample (presence of at least one of the following signs):
• positive reaction to leukocyte esterase based on the results of the common urineexamination;
• number of leukocytes ≥ 10 cells/mm3 in non-centrifuged urine sample;
• number of leukocytes ≥ 10 cells / per HPF in the urine sediment. 6. At least one ofthe following associated risks: • periodic bladder catheterization or the presence ofa permanent bladder catheter, ureters (ureter stent), kidneys (nephrostoma) (cathetersinstalled more than 24 hours prior to screening should be removed or replaced prior tocollection of an urine sample for analysis and sowing, unless removal or replacementis considered unsafe or contraindicated);
• presence of known functional or anatomical abnormalities in the urinary system,including malformations, neurogenic bladder, presence of residual urine volume ≥ 100 ml, stricture after surgery and/or malformations of the urinary tract,separate drainage of the kidney and/or bilateral nephrostomy tubes;
• complete or partial obstructive uropathy (e.g. nephrolithiasis, tumor, fibrosis,urethral stricture, cystolithiasis) that is expected to be subjected totherapeutic or surgical treatment during treatment with the drug under study (until the end of therapy);
• azotemia defined as blood urea nitrogen level (BUN) > 20 mg/dl, blood urea level > 42.8 mg/dl, or serum creatinine > 1.4 mg/dl due to known kidney disease inanamnesis;
• chronic urinary retention in men, e.g. due to the previously diagnosed benignprostatic hypertrophy.

7. Obtaining the patient's initial urine sample for sowing within 24 hours beforerandomization (patients can be randomized in this study and start therapy withthe drug under study before the results of the initial urine culture become knownto the researcher).
8. A reasonable assumption that any installed urinary device (e.g., nephrostomycatheter, permanent stents) will be surgically removed or replaced before orwithin 24 hours of randomization (temporary catheters that were installed morethan 24 hours before screening should be removed or replaced before urine samplecollection for analysis and sowing).
9. Recurrent complicated urinary tract infection within 12 months before thestudy (presence of complicated urinary tract infection in anamnesis with afrequency of more than twice per year).
10. Suspected infection caused by multiresistant strains of P. aeruginosa,inefficiency of previous treatment.
11. High risk of complicated UTI caused by P. aeruginosa (e.g. pseudomonalcomplicated UTI in anamnesis, therapy of 20 mg or more with prednisone orequivalent steroid and other risk factors that are taken into account by theresearcher.
12. Prognostic life expectancy of the patient with effective antibiotic therapyand proper maintenance treatment is estimated by the researcher to be at least 6months.
13. Women who capable of childbirth (i.e. not in menopause and not surgicallysterilized) should have a negative pregnancy test result before randomization.Participants in the study who are capable of procreation, or sexual partners ofparticipants who are capable of childbirth, should agree to the continued use ofa highly effective method of contraception from the beginning of screening to theend of the study (medical and pedagogical observations) (highly effective methodsof contraception include hormonal implants, plasters, injectable hormones, oralhormonal contraceptives, intrauterine systems, approved cervical ring, priorbilateral ovariectomy, prior hysterectomy, previous bilateral tubal ligation,true abstinence from sexual activity (if confirmed by the researcher), orvasectomy with a partner.
14. Male participants of the study will need to use condoms with spermicideduring sexual intercourse during screening up to the end of the study in case ofpossible and even existing pregnancy of the sexual partner.

Exclusion Criteria:

• 1. Presence of any known or suspected disease, or condition that may distort theassessment effectiveness, including, but not limited to, the following:
• perinephral abscess;
• corticomedullary kidney abscess;
• any history of pelvic or urinary tract injury within 30 days prior to the study;
• polycystic kidney disease;
• chronic vesicoureteral reflux;
• prior or planned kidney transplantation;
• dialysis patients, including those under hemodialysis, peritoneal dialysis orcontinuous venovenous hemofiltration (CVVH);
• previous or planned cystectomy or surgery on the loop of ileum;
• presence of a known or suspected infection that is caused by fungi (e.g.candiduria) or mycobacteria (e.g. urogenital tuberculosis).

2. Presence of suspected or confirmed acute bacterial prostatitis, orchitis,epididymitis or chronic bacterial prostatitis determined by anamnesis and/orgeneral medical examination.
3. Macrogematuria requiring treatment other than administration of the drug understudy or removal, or replacement of the urinary catheter.
4. Surgery on the urinary tract within 7 days before randomization, or surgery onthe urinary tract planned during the period of study (except surgicalintervention necessary to remove the obstruction or placement of the stent orholding of a nephrostomy until the end of treatment (medical and pedagogicalobservations).
5. Renal function in screening evaluated by creatinine clearance as < 50 ml / minusing the Cocroft-Gault formula and serum creatinine values obtained in a locallaboratory.
6. Source of infection diagnosed within 7 days prior to randomization with knownextra-renal origin, such as endocarditis, osteomyelitis, abscess, burn urinarytract infection; meningitis or pneumonia.
7. Any signs of sepsis, including shock or deep arterial hypotension, which isdefined as SBP < 90 mm Hg or a pressure reduction of > 40 mm Hg from the initiallevel (if known) not reacting to the load with a liquid.
8. Pregnant or breastfeeding women. 9. Established epileptic syndrome requiringongoing treatment with an anticonvulsant drug, which will not allow the patientto comply with the treatment regimen according to the Study Protocol. Patientswith a history of epilepsy or those receiving stable therapy (i.e. unchangedtherapy for 30 days) with a well-controlled epileptic syndrome (i.e. with norecurrence within the last 30 days) may be considered for admission to the study.
9. Treatment with antitumor chemotherapeutic drugs, treatment withimmunosuppressive therapy for transplantation, or drugs preventing rejection ofthe transplant within 30 days prior to randomization.
10. Signs of severe disease or liver dysfunction, including confirmed viralhepatitis or hepatic encephalopathy.
11. AST or ALT > 3 x ULN (upper limit of normal) or total bilirubin > 1.5 x ULNat screening.
12. Administration of any long-acting systemic antibiotic (i.e. with a frequencyof less than once per day) for less than 12 hours prior to randomization. However, the following patients may be included:

• who have received antimicrobial therapy for > 24 hours and have not responded totreatment (i.e. signs and symptoms have worsened) and have documented complicated UTIscaused by pathogen microorganisms resistant to previous therapy;

• who developed signs and symptoms of complicated UTI in the administration of systemicantibiotics for other indications, including antimicrobial prophylaxis againstrecurrent UTI;
• who received short-acting systemic antibiotic therapy (i.e. with frequency ofadministration more than once per day) for 24 hours before randomization, but not lessthan 12 hours prior to randomization.

14. Need for additional systemic antimicrobial therapy at the time of randomization (including antibiotic, antifungal therapy), other than treatment with the drug understudy, except for a single oral administration of any antifungal drug for thetreatment of vaginal candidiasis.
15. Likelihood of the need for an antibiotic to prevent complicated UTI during patientparticipation in the study (from randomization to medical and pedagogicalobservations).
16. Impossibility of removal or replacement of temporary catheters installed in morethan 24 hours prior to the screening from the perspective of evaluating the safety ofthe patient or presence of contraindications to manipulation (temporary cathetersinstalled more than 24 hours prior to the screening should be removed or replacedprior to collecting the urine sample for analysis and sowing).
17. History of HIV infection. 18. Presence of significant immunodeficiency or immunedeficiency, including hematologic malignant disease, bone marrow transplantation orreceiving immunosuppressive therapy, such as chemotherapy for cancer, administrationof drugs to prevent graft rejection and long-term use of systemic corticosteroids (equivalent to the use of prednisone or equivalent systemic drug at a dose ≥ 20 mg/dayfor ≥ 2 weeks).
18. Presence of neutropenia (absolute number of neutrophils < 1000/mm3) based on theresults of the screening analysis in the central laboratory.
19. Presence of thrombocytopenia (especially in patients diagnosed with disseminatedintravascular coagulation or risk of serious bleeding) 50,000 platelets/mm3 confirmedon the basis of indicators obtained in the central laboratory during screening.
20. Lactose intolerance, lactose deficiency or glucose-galactose absorption, severehypersensitivity or allergic reaction to β-lactam antibiotics, L-arginine, localanesthetics, antiarrhythmics or to the components of the drug in anamnesis.
21. Presence of any contraindications to the use of β-lactam antibiotics (cephalosporins, penicillins, carbapenems or monobactams), to administration ofauxiliary substances that are part of the relevant dosage forms.
22. Participation in another clinical trial using the drug or device under study forthe last 90 days prior to randomization.
23. Inability or unwillingness to comply with the requirements of the Study Protocol.
24. Any patients previously randomized into this study.