Sulopenem Followed by Sulopenem-etzadroxil/Probenecid vs Ertapenem Followed by Cipro for Complicated UTI in Adults
Condition: Complicated Urinary Tract Infections
MeSH terms: Urinary Tract Infections
Intervention: Sulopenem; Sulopenem-Etzadroxil/Probenecid; Ertapenem; Ciprofloxacin; Amoxicillin-clavulanate
Intervention description: Antibiotic therapy for complicated UTI; Antibiotic therapy for complicated UTI; Antibiotic therapy for complicated UTI; Antibiotic therapy for complicated UTI; Antibiotic therapy for complicated UTI
Intervention MeSH terms: Amoxicillin; Ciprofloxacin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination; Ertapenem; Lactams; Probenecid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1395.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a prospective, phase 3, randomized, multicenter, double-blind, double-dummy study to
      compare the efficacy and safety of sulopenem followed by sulopenem-etzadroxil/probenecid
      versus ertapenem followed by ciprofloxacin for the treatment of complicated urinary tract
      infections (cUTI) in adults.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adults ≥18 years of age with more than 24 hours of urinary symptoms attributable to a
             UTI

          2. Able to provide informed consent

          3. Clinically documented pyelonephritis or complicated urinary tract infection:

               1. Pyelonephritis with normal anatomy

               2. Complicated UTI as defined by one or more of the following factors:

             i. The presence of an indwelling catheter ii. >100 mL of residual urine after voiding
             iii. Neurogenic bladder iv. Obstructive uropathy due to nephrolithiasis, tumor or
             fibrosis v. Azotemia 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:

               1. Rigors, chills or fever/hypothermia

               2. Flank pain or pelvic pain

               3. Nausea or vomiting

               4. Dysuria, urinary frequency or urinary urgency

               5. Costovertebral angle tenderness on physical examination

          5. A mid-stream urine specimen with:

               1. a dipstick analysis positive for nitrite AND

               2. evidence of pyuria as defined by either: i. a dipstick analysis 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/high-powered field in urine sediment

        Exclusion Criteria

          1. Receipt of effective antibacterial drug therapy for complicated urinary tract
             infection (cUTI) for a continuous duration of more than 24 hours during the previous
             72 hours. 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) 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 dialysis

         13. Acute or chronic prostatitis

         14. High risk for cUTI caused by Pseudomonas sp. (eg,. history of prior UTI due to
             Pseudomonas species, recent steroid use, others)

         15. Chronic indwelling catheters or stents

         16. Ileal loops or vesico-urethral 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, 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 must agree to use of an effective barrier method of contraception during
             the study and for 14 days post treatment

         25. Patients known to have a history of liver or kidney disease or neutropenia as defined
             by the following baseline laboratory criteria:

               -  Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) > 3 X Upper
                  Limit of Normal

               -  Total bilirubin > 2 X Upper Limit of Normal

               -  Neutropenia (<1000 cells/mm3)

         26. Patients participating in any other clinical study that involved the administration of
             an investigational medication

         27. Patient immunocompromised

         28. Patients unlikely to comply with the protocol

         29. Patients considered unlikely to survive the 4-week study period or has a rapidly
             progressive or terminal illness