Complicated urinary tract infection
Conditions
Sponsors
Iterum Therapeutics International Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adults =18 years of age with more than 24 hours of urinary symptoms attributable to a UTI 2. Patient or the patient’s legally acceptable representative able to provide a signed written informed consent prior to any study-specific procedures. 3. Clinically documented pyelonephritis or complicated urinary tract infection: a) Pyelonephritis with normal anatomy, OR b) Complicated UTI as defined by one or more of the following factors: i. The presence of an indwelling urethral catheter ii. >100 mL of residual urine after voiding iii. Neurogenic bladder iv. Obstructive uropathy due to nephrolithiasis, tumor or fibrosis v. Azotemia (blood urea nitrogen [BUN] > 20 mg/dL and BUN/creatinine ratio 100.4ºF or 38ºC, or =65 years) yes F.1.3.1 Number of subjects for this age range 460
Exclusion criteria
Exclusion criteria: 1. Receipt of effective antibacterial drug therapy for cUTI for a continuous duration of more than 24 hours in the 72 hours prior to randomization. Patients who have objective documentation of clinical progression of cUTI while on antibacterial drug therapy, or patients who received antibacterial drugs for surgical prophylaxis and then develop cUTI, may be appropriate for enrollment. 2. Subjects with an organism isolated from the urine within the last year known to be resistant to ertapenem. 3. Severe structural or functional urinary tract abnormality responsible for an intractable infection which in the opinion of the investigator would require > 10 days of therapy or post-treatment prophylaxis (eg. patients with chronic vesiculo-ureteral reflux). 4. Uncomplicated UTI 5. Patients with paraplegia/quadriplegia 6. Hypotension with systolic blood pressure 40 mg/day equivalent prednisolone for 5 days or more in the 30 days prior to randomization), multiple sclerosis, chronic supra-pubic catheter) 15. Chronic indwelling catheters or stents (>2 weeks) 16. Ileal loops or vesico-ureteral reflux 17. Recent trauma to the pelvis or urinary tract within the prior 30 days 18. History of seizures 19. Patients with a history of blood dyscrasias 20. Patients with a history of uric acid kidney stones 21. Patients with acute gouty attack 22. Patients on chronic methotrexate therapy 23. Females of child-bearing potential who are unable to take adequate contraceptive precautions (refer to Section 4.4.1), have a positive pregnancy test result within 24 hours of study entry, are otherwise known to be pregnant, or are currently breastfeeding an infant. 24. Male subjects who do not agree to use an effective barrier method of contraception (refer to Section 4.4.2) during the study and for 28 days after dosing 25. Patient is kno
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of sulopenem IV followed by oral sulopenem-etzadroxil plus probenecid with ertapenem IV followed by oral ciprofloxacin or amoxicillin-clavulanate for the treatment of complicated urinary tract infection at Day 21 (± 1 day; test of cure [TOC visit]).; Secondary Objective: • To compare the per-patient microbiologic response across treatment groups. • To compare the efficacy outcomes at relevant time points. • To assess the safety profile of treatment with each regimen. • To assess the population PK profile of sulopenem and/or sulopenem-etzadroxil co-administered with probenecid. ; Primary end point(s): A patient will be defined as a responder at Day 21 (± 1day; TOC) if the following criteria are met: • The patient is alive • Resolution of dysuria, urinary frequency, urinary urgency, suprapubic pain, and flank pain or pelvic pain if present at trial entry and no new symptoms per the patient’s questionnaire - Baseline symptoms associated with anatomic abnormalities that predispose to cUTI (e.g., symptoms associated with the presence of an indwelling urinary catheter) do not need to be resolved. • The patient has received no rescue therapy for cUTI - If an antibiotic is given for other reasons then the patient will not be considered a non-responder for cUTI • The bacterial pathogen found at >= 10^5 CFU/mL in the trial entry urine culture is reduced to <10^3 CFU/mL in the urine culture taken at the specified study visit and the blood culture is eradicated if one was present at baseline. All other patients will be considered non-responders unless data are unavailable to determine if the patient is a responder or non-responder. In this case, the patient will be considered as having an indeterminate response. Deaths not due to cUTI wi | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: At Day 21 (± 1day; TOC); Secondary end point(s): Microbiologic Response is assessed at Day 21 (± 1day; TOC) using the definitions listed below: Eradication: A urine culture taken within 48 hours prior to randomization (baseline) and compared with the culture from the Day 5 visit, Day 10 (± 1 day; or Day 11-14 (± 1 day) for patients with bacteremia at Baseline) visit, or Day 21 (± 1day; TOC) visit showed that the urine culture obtained at the relevant visit demonstrated <103 CFU/mL of the original uropathogen. For patients with bacteremia at Baseline, the follow-up repeat blood cultures are sterile. Persistence: A uropathogen present at baseline grew at =103 CFU/mL at the time-point of analysis, i.e. Day 5, Day 10 (± 1 day; or Day 11-14 (± 1 day) for patients with bacteremia at Baseline), or Day 21 (± 1day; TOC). For patients with bacteremia at Baseline, follow-up blood cultures after 72 hours of treatment show growth of baseline pathogen. Persistence with increasing MIC: A urine culture taken after at least 2 full days of treatment grew =103 CFU/mL of the original uropathogen species and displayed =4-fold higher MIC to study drug therapy after treatment with study therapy at Day 5, Day 10 (± 1 day; or Day 11-14 (± 1 day) for patients with bacteremia at Baseline), or Day 21 (± 1day; TOC) respectively. For patients with bacteremia at Baseline, follow-up blood cultures after 72 hours of treatment show growth of baseline pathogen and displayed =4-fold higher MIC to study drug therapy. Indeterminate: Patient was lost to follow-up or an assessment was not undertaken such that no urine culture was obtained; culture is contaminated or culture results could not be interpreted for any reason, at either the Day 5, Day 10 (± 1 day; or Day 11-14 (± 1 day) for patients with bactere | — |
Countries
Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Hungary, Latvia, Poland, Russian Federation, Serbia, Slovakia, Ukraine, United States
Contacts
Public ContactFerenc Szucs, project manager
PSI CRO AG
Outcome results
None listed