Health Condition 1: N390- Urinary tract infection, site notspecified
Conditions
Interventions
Intervention1: Cefepime-tazobactam (FEP-TAZ): Dose - Cefepime-tazobactam 4 g (2 g cefepime + 2 g tazobactam)
Route of administration - Intravenous Frequency - Every eight hours Total duration - 7 to
Sponsors
Ms Wockhardt Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male or female = 18 years old 2. Provide a signed written informed consent prior to any study-specific procedures 3. Meet the following clinical criteria for either cUTI or AP: A. cUTI: a. Have at least TWO of the following new-onset or worsening symptoms or signs: Fever (oral, tympanic, or rectal temperature more than 38?C [more than 100.4?F]), which must be observed and documented by a health care provider Nausea or vomiting Dysuria, increased urinary frequency, or urinary urgency Lower abdominal, suprapubic, or pelvic pain b. Have at least ONE of the following complicating factors: -Use of intermittent urethral catheterization or presence of an indwelling urethral catheter (Note: indwelling urethral catheters that have been in place for more than 24 hours prior to Screening must be removed or replaced prior to collection of the screening urine for urinalysis and culture, unless removal or replacement is considered unsafe or contraindicated) -Current known functional or anatomical abnormality of the urogenital tract, including anatomic malformations or neurogenic bladder, or with a post-void residual urine volume of more than and equal to 100 mL -Complete or partial obstructive uropathy (e.g., nephrolithiasis, tumor, fibrosis, urethral stricture) that is expected to be medically or surgically treated during study drug therapy (prior to EOT) -Azotemia, defined as BUN more than 20 mg/dL (or blood urea more than 42.8 mg/dL) or serum creatinine more than 1.4 mg/dL, due to known prior intrinsic renal disease -Documented history of urinary retention in men (e.g., previously diagnosed benign prostatic hypertrophy) B. AP, defined as acute flank pain (onset within 7 days prior to randomization) or costovertebral angle (CVA) tenderness on physical examination, plus at least ONE of the following new-onset or worsening symptoms or signs: -Fever (oral, tympanic, or rectal temperature more than 38?C [more than 100.4?F]), which must be observed and documented by a health care provider -Nausea or vomiting -Dysuria, increased urinary frequency, or urinary urgency Note: If criteria for both cUTI and AP are met, cUTI will be considered the study entry diagnosis for randomization and analysis purposes. 4. Evidence of pyuria within 48 hours prior to randomization, as determined by an adequate clean catch urine specimen for culture or other appropriate method to collect a urine culture that minimizes risk of bacterial contamination with ONE of the following findings: -Positive leukocyte esterase on urinalysis, (where positive result is at least or moderate as indicated on a urine dipstick) -WBC count more than and equal to 10 cells/mm3 in unspun urine -WBC count more than and equal to 10 cells/ HPF in urine sediment (spun urine) Note: The screening/baseline urine sample (within 48 hours prior to randomization) will be submitted for culture; however, subjects may be randomized and administered study drug therapy prior to knowledge of screening/baseline urine culture results. 5. If known, the screening/baseline urine culture taken within 48 hours prior to randomization contains more than and equal to 105 CFU/mL of a Gram-negative uropathogen likely to be susceptible to meropenem 6. Expectation, in the judgment of the Investigator, that any implanted urinary
Exclusion criteria
Exclusion criteria: 1.Known or suspected disease or condition that, in the opinion of the Investigator, may confound the assessment of efficacy, including but not limited to the following: -Perinephric or renal abscess -Uncomplicated lower UTI -Recent trauma to the pelvis or urinary tract -Polycystic kidney disease -Chronic vesicoureteral reflux -Previous or planned cystectomy or permanent urinary diversion (e.g., ileal loop, cutaneous ureterostomy) -Acute or chronic bacterial prostatitis, orchitis, or epididymitis -Concurrent non-renal source of infection (e.g., endocarditis, osteomyelitis, abscess, meningitis, pneumonia) -Previous or planned renal transplant or subject requiring hemodialysis -cUTI or AP that is known at Screening to be caused by a pathogen that is resistant to meropenem, including infection caused by fungi (e.g., candiduria) or mycobacteria (e.g., urogenital tuberculosis) 2.Receipt of potentially effective systemic antibacterial therapy within 72 hours prior to randomization, with the exception of any of the following: -Receipt of a single dose of an allowed short acting antibacterial agent within 72 hours prior to randomization. For subjects without documentation of failure on this prior therapy and/or documented uropathogen resistant to this prior therapy, this exception will be capped at a maximum of 25 percent of enrollment. -Receipt of more than 48 hours of prior antibiotic therapy and in the Investigators opinion, failed that prior antibiotic therapy -Documented to have cUTI or AP caused by a pathogen that is not susceptible to the prior antibiotic therapy 3. Rapidly progressive or terminal illness with a high risk of mortality due to any cause, including but not limited to acute hepatic failure, respiratory failure, or septic shock, such that the subject is unlikely to survive the study period 4. Pregnant or breastfeeding women 5. Likely to require more than 10 days of antibiotic treatment to cure the current acute cUTI, or likely to receive any additional systemic antimicrobial therapy during the study period (including antibacterial, antimycobacterial, or antifungal therapy or prophylaxis) other than study drug, with the exception of (1) a single oral dose of any antifungal treatment for vaginal candidiasis, or (2) a glycopeptide (e.g., vancomycin), oxazolidinone (e.g., linezolid), or daptomycin given for a Gram-positive infection 6. 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) 7. History of epilepsy or known seizure disorder requiring current treatment with anti-seizure medication 8. Creatinine clearance less than 30 mL/min or requirement for hemodialysis or CVVH 9. Current or anticipated neutropenia defined as less than 500 neutrophils/mm3 , or platelet count less than 50,000 per microliter 10. Screening serum total bilirubin more than and equal to 2 times the ULN (unless elevated indirect bilirubin due to known Gilberts syndrome), or AST or ALT more than and equal to 5 times ULN, or alkaline phosphatase more than and equal to 2 times ULN 11. History of Clostridioides difficile associated disease within 6 months prior to enrolment 12. History of serious or significant hypersensitivity or allergic reaction
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the overall safety and tolerability of FEP-TAZ in the Safety populationTimepoint: Test of Cure visit - Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| ? To assess the clinical outcome at EOT (MITT and mMITT populations) and at TOC (mMITT and CE populations) ? To assess the microbiological outcome at EOT (mMITT population) and at TOC (mMITT and ME populations) ? To assess the by-pathogen clinical (mMITT and CE populations) and microbiological outcomes (mMITT and ME populations) at TOCTimepoint: Randomization/Day 1: Day 1 is calendar day of first dose of study drug ? Day 1 through Day 10: Treatment period. All subjects will receive 7 to 10 days of study drug ? EOT: Last day of study drug administration (FEP-TAZ or meropenem), or within 24 hours after completion of the last infusion of study drug ? TOC: Day 17 ? 2 days, inclusive ? LFU: Day 26 ? 4 days. The LFU assessments may be conducted via telephone contact or by another interactive technology | — |
Countries
India
Contacts
Public ContactDr Sachin Bhagwat
Wockhardt
Outcome results
None listed