Efficacy and Safety Study of Eravacycline Compared With Ertapenem in Participants With Complicated Urinary Tract Infections
Condition: Complicated Urinary Tract Infections
MeSH terms: Infections; Communicable Diseases; Urinary Tract Infections
Intervention: Eravacycline; Ertapenem; Placebo; Levofloxacin
Intervention MeSH terms: Levofloxacin; Ertapenem
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1205.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of
      eravacycline compared to ertapenem in treating participants with complicated urinary tract
      infections (cUTI).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female participant with either:

               1. Pyelonephritis and normal urinary tract anatomy (approximately 50% of the total
                  population), or

               2. cUTI with at least one of the following conditions associated with a risk for
                  developing cUTI:

                    -  Indwelling urinary catheter

                    -  Urinary retention (at least approximately 100 milliliters (mL) of residual
                       urine after voiding)

                    -  History of neurogenic bladder

                    -  Partial obstructive uropathy (for example, nephrolithiasis, bladder stones,
                       and ureteral strictures)

                    -  Azotemia of renal origin (not congestive heart failure [CHF] or volume
                       related) such that the serum blood urea nitrogen [BUN] is elevated (>20
                       milligrams [mg]/deciliters [dL]) and the serum BUN:creatinine ratio is <15

                    -  Surgically modified or abnormal urinary tract anatomy (for example, bladder
                       diverticula, redundant urine collection system) except urinary tract surgery
                       within the last 30 days (placing of stents or catheters is not considered to
                       be surgical modification)

          2. At least 18 years of age at time of consent

          3. Able to provide informed consent

          4. At least two of the following signs or symptoms:

               1. Chills, rigors, or warmth associated with fever or hypothermia

               2. Flank pain (pyelonephritis) or pelvic pain (cUTI)

               3. Nausea or vomiting

               4. Dysuria, urinary frequency, or urinary urgency

               5. Costo-vertebral angle tenderness on physical examination

          5. Urine specimen with evidence of pyuria

               1. Dipstick analysis positive for leukocyte esterase (where positive result is at
                  least "++" as indicated on the urine dipstick provided in the laboratory kit), or

               2. ≥10 white blood cells (WBCs) per cubic millimeter, or

               3. ≥10 WBCs per high power field

          6. If male: must agree to use an effective barrier method of contraception (for example,
             condom) during the study and for 14 days following the last dose if sexually active
             with a female of childbearing potential

          7. If female, not pregnant or nursing or, if of childbearing potential: must commit to
             either use at least two medically accepted, effective methods of birth control (for
             example, condom, spermicidal gel, oral contraceptive, indwelling intrauterine device,
             hormonal implant /patch, injections, approved cervical ring) during study drug dosing
             and for 14 days following last study drug dose or practicing sexual abstinence

        Exclusion Criteria:

          1. Use of systemic antibiotics effective in cUTI within 72 hours prior to enrollment
             except under the following circumstances:

               1. Participants with suspected acute cUTI who have received a single dose of
                  effective non-study antibiotics for the acute cUTI

               2. Signs and symptoms of cUTI developed while on the antibiotic for another
                  indication

          2. History of an ertapenem-resistant urinary tract infection within 1 year of enrollment

          3. Likely to require >10 days of antibiotic treatment to cure the acute cUTI or likely to
             receive ongoing antibacterial drug prophylaxis prior to the Follow Up visit (21-28
             days after randomization) [for example, participants with chronic vesiculo-ureteral
             reflux]

          4. Unlikely to survive at least through the duration of the study

          5. Hypotension, systolic blood pressure ≤90 millimeters of mercury [mmHg]

          6. Complicated pyelonephritis with complete obstruction or known or suspected renal or
             perinephric abscess, emphysematous pyelonephritis, or Any condition likely to require
             surgery to achieve cure (this does not include procedure to place catheters or obtain
             diagnosis)

          7. Known or suspected urinary fungal infection

          8. Uncomplicated lower urinary tract infections

          9. Suspected or confirmed active prostatitis, or currently under treatment for
             prostatitis

         10. High risk for cUTI due to Pseudomonas (for example, history of prior cUTIs due to
             Pseudomonas, ≥20 mg once a day prednisone or equivalent steroid, and other risk
             factors as perceived by the Investigator)

         11. History of renal transplantation

         12. Presence of an ileal loop

         13. Any history of trauma to the pelvis or urinary tract occurring within 30 days of
             screening

         14. Indwelling urinary catheters present at screening which are not expected to be removed
             or replaced within 72 hours of enrollment (for example, nephrostomy tubes, stents,
             urethral and suprapubic catheters).

         15. Known concomitant human immunodeficiency virus (HIV) infection with CD4 counts below
             200 within the last six months, or an acquired immune deficiency syndrome (AIDS)
             defining diagnosis within the last six months

         16. Neutropenia (Absolute neutrophil count <1,000 polymorphonuclear leukocytes
             [PMNs]/microliters [µL])

         17. Participation in a study with an experimental drug or device within 30 days prior to
             enrollment

         18. Known or suspected hypersensitivity to tetracyclines, carbapenems, or β-lactams

         19. History of seizures

         20. Any other unstable or clinically significant concurrent medical condition (for
             example, immunosuppressive therapy, chemotherapy, class IV heart or lung disease, end
             stage renal disease, or requiring hemodialysis) that would, in the opinion of the
             Investigator, jeopardize the safety of a participant and/or their compliance with the
             protocol