Last updated on August 2019

A prospective, Phase 3, randomized, multi-center, double-blind, double dummy study of the efficacy, tolerability and safety of intravenous sulopenem followed by oral sulopenem-etzadroxil with probenecid versus intravenous ertapenem followed by oral ciprofloxacin or amoxicillin-clavulanate for treatment of complicated urinary tract infections in adults.

Are you eligible to participate in this study?

You may be eligible for this study if you meet the following criteria:

  • Conditions: Urinary tract infection
  • Age: Between 18 - 100 Years
  • Gender: Male or Female

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 <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

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 < 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 amoxicillinclavulanate 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. Patients known to have a history of liver disease or neutropenia as defined by the following baseline 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 immunodeficiency virus (HIV) infection, with either a recent (in the past 6 months) acquired immune deficiency syndrome-defining condition or a CD4 + T lymphocyte count <200/mm3

b. Systemic or hematological malignancy requiring chemotherapeutic or radiation/immunologic interventions within 6 weeks prior to randomization or anticipated to begin prior to completion of study

c. Immunosuppressive therapy, including maintenance corticosteroid therapy (>40 mg/day equivalent prednisolone for 5 days or more in the 30 days prior to randomization).

28. Patient unlikely to comply with protocol e.g., uncooperative attitude, inability to return for follow-up visits, and unlikely to complete the study.

29. Patient considered unlikely to survive the 4-week study period or has a rapidly progressive or terminal illness, including septic shock that was associated with a high risk of mortality.

Recruitment Status: Closed

Brief Description Eligibility Contact Research Team

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