Adults With Complicated Urinary Tract Infections including infection reaching their kidneys will be treated with either cefepime in combination with AAI101 or Piperacillin/Tazobactam. Neither the participants nor the research staff know the identity of the administered drug. cefepime/AAI101 or Piperacillin/Tazobactam alone will be assigned using a method based on chance.
- Conditions
- Complicated urinary tract infections including acute pyelonephritisMedDRA version: 20.1 Level: PT Classification code 10037597 Term: Pyelonephritis acute System Organ Class: 10021881 - Infections and infestationsMedDRA version: 20.0 Level: HLT Classification code 10046577 Term: Urinary tract infections System Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2017-004868-35-HU
- Lead Sponsor
- Allecra Therapeutics SAS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 1044
1. Male or female patients =18 years of age at the time of signing of informed consent;
2. Expectation that the patient’s cUTI or AP will require hospitalization and initial treatment withat least 7 days of i.v. antibiotics;
3. Female patients who are no longer of childbearing potential must meet 1 of the following
criteria: (a) Women =50 years of age who are considered post-menopausal as they have beenamenorrhoeic for =12 months following cessation of all pharmaceutical or exogenoushormonal treatment; (b) Women <50 years of age who are considered post-menopausal as they have beenamenorrhoeic for =12 months following cessation of all pharmaceutical or exogenous treatment and if follicle-stimulating hormone (FSH) levels are in the post-menopausal range. If the FSH levels are not available at the time of randomization, the patient must have a negative pregnancy test and agree to use highly effective contraception methods until the FSH result is available; or
(c) Permanent sterilization, defined as hysterectomy, bilateral oophorectomy, or bilateral salpingectomy;
4. Female patients of childbearing potential must have a negative urine and/or serum pregnancy test (serum ß-human chorionic gonadotropin) within 1 day prior to study entry;
5. Male patients, female patients receiving hormone replacement therapy (HRT), and female patients of childbearing potential must agree to use highly effective contraception methods as defined below: NOTE: Female patients who are no longer of childbearing potential (i.e., confirmed to be permanently sterile as defined above or post-menopausal) and patients who are exclusively in same-sex relationships will not be required to use contraception. (a) Male patients and their partners of childbearing potential or partners sterilized by tubal ligation, female patients receiving HRT, female patients who have been sterilized by tubal ligation, and female patients of childbearing potential are required to use a condom (male or female) in conjunction with spermicidal gel, foam, cream, film, or suppository from the time of dosing until 90 days after the last dose; and (b) Male patients and their partners of childbearing potential and female patients of childbearing potential are required to use an additional highly effective form of contraception from the time of first dose until 90 days after the last dose. Additional highly effective methods of contraception include the following: Diaphragm or cervical vault cap in conjunction with spermicidal gel, foam, cream, film, or suppository;/ Male sterilization (for female patients, the vasectomized male partner should be the sole partner for that patient);/ Intrauterine device; or/ Established use of oral, injected, or implanted hormonal methods of contraception;
6. 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;
7. Clinical signs and/or symptoms of cUTI (Complicated Urinary Tract Infection) or AP (Acute Pyelonephritis), as defined in Protocol, Table 1;
NOTE: If the criteria for both cUTI and AP are met, the infection type will be considered cUTI for randomization and analysis purposes.
8. Have a baseline urine culture specimen obtained within 48 hours p
1. Known urine culture with Gram positive primary pathogen at > or = 10[5] colony-forming units (CFU)/mL (not contaminant) or suspected Gram-positive pathogen by Gram staining (Note: Gram staining is optional)
2. 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 BLIs (e.g., tazobactam, sulbactam, or clavulanic acid);
3. In the opinion of the Investigator, the patient is considered unlikely to survive the approximately 6-week study period;
4. Weight >180 kg;
5. Concurrent infection that would interfere with evaluation of response to the study antibiotics;
6. 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;
7. 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 (Exception defined in Protocol, Exc. Criteria 7)
8. Complicated urinary tract infection (UTI) known at study entry to be caused by pathogens resistant to the study antibiotics;
9. Likely to require the use of an antibiotic for cUTI or AP prophylaxis during the patient’s participation in the study;
10. Intractable UTI at baseline that the Investigator anticipates would require >14 days of study drug therapy;
11. Complete, permanent obstruction of the urinary tract that is not anticipated to be medically or surgically relieved during i.v. study therapy and before EOT;
12. Gross hematuria requiring intervention other than administration of study drug or removal or exchange of a urinary catheter;
13. Presence of any known or suspected disease or condition that, in the opinion of the Investigator, may confound the assessment of efficacy. (Explained in Protocol, Exc. Criteria 13)
14. Suspected or confirmed acute bacterial prostatitis, orchitis, epididymitis, or chronic bacterial prostatitis as determined by history and/or physical examination;
15. 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 (MDRD) study equation (see Appendix D);
16. Urinary tract surgery within 7 days prior to randomization 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);
17. Any condition or circumstance that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of study data;
18. Any rapidly progressing disease or immediately life-threatening illness, including acute hepatic failure and respiratory failure;
19. Presence of sepsis, producing life-threatening organ dysfunction, defined as =2 of the following criteria: a. Systolic blood pressure =100 mmHg that is not responsive to fluid challenge; b. Respiratory rate =22 brea
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method