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]).
- Conditions
- Complicated urinary tract infectionMedDRA version: 20.0Level: LLTClassification code 10021872Term: Infection urinary tractSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2017-003772-31-SK
- Lead Sponsor
- Iterum Therapeutics International Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1381
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 <15) due to intrinsic renal disease
vi. Urinary retention in men possibly due to benign prostatic hypertrophy
vii. Surgically modified or abnormal urinary tract anatomy
4. At least two of the following signs or symptoms:
a) Rigors, chills or fever/hypothermia with temperature (oral, rectal, tympanic, temporal) >100.4ºF or 38ºC, or <95ºF or 35ºC
b) Flank pain or pelvic pain
c) Nausea or vomiting
d) Dysuria, urinary frequency or urinary urgency
e) Costovertebral angle tenderness on physical examination
5. A mid-stream urine specimen with:
a) a machine-read dipstick positive for nitrite AND
b) evidence of pyuria as defined by either:
i. a machine-read dipstick positive for leukocyte esterase AND/OR
ii. at least 10 white blood cells per cubic millimeter on microscopic analysis of unspun urine AND/OR
iii. White blood cell count =10 cells/HPF in urine sediment
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 921
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 460
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 < 90 mm Hg
7. Complicated UTI associated with complete obstruction, emphysematous pyelonephritis, known or suspected renal or perinephric abscess or expected to require surgical intervention (not placement of catheters, stents or nephrostomy tubes) to achieve cure
8. Patients with a known history of myasthenia gravis
9. Patients who require concomitant administration of tizanidine or valproic acid
10. Patients with a history of allergy to carbapenems or quinolones or amoxicillin-clavulanate or other beta-lactams, or hypersensitivity to probenecid
11. Renal transplantation
12. Patients requiring hemodialysis, hemofiltration or peritoneal dialysis
13. Acute or chronic prostatitis
14. High risk for cUTI caused by Pseudomonas spp. (eg,. history of prior UTI due to Pseudomonas spp, recent steroid use (>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 known to have a history of liver disease or neutropenia as defined by the following laboratory criteria:
a. Alanine aminotransferase (ALT)or aspartate aminotransferase (AST) >3 X Upper Limit of Normal (ULN)
b. Total bilirubin >2 X ULN
c. Neutropenia (absolute neutrophil count <1000 cells/mm3)
26. Patients participating in any other clinical study that involved the administration of an investigational medication at the time of presentation, during the course of the study, or who had received treatment with an investigational medication in the 30 days prior to study enrollment, or had previously been randomized to this study or had been treated with sulopenem.
27. Patients immunocompromised as evidenced by any of the following:
a. Human immunode
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