A Study of Efficacy and Safety of Intravenous Cefiderocol (S-649266) Versus Imipenem/Cilastatin in Complicated Urinary Tract Infections

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02321800
• Date of registration: 11/11/2014
• Prospective Registration: Yes
• Primary sponsor: Shionogi
• Public title: A Study of Efficacy and Safety of Intravenous Cefiderocol (S-649266) Versus Imipenem/Cilastatin in Complicated Urinary Tract Infections APEKS-cUTI
• Scientific title: A Multicenter, Double-blind, Randomized, Clinical Study to Assess the Efficacy and Safety of Intravenous S-649266 in Complicated Urinary Tract Infections With or Without Pyelonephritis or Acute Uncomplicated Pyelonephritis Caused by Gram-Negative Pathogens in Hospitalized Adults in Comparison With Intravenous Imipenem/Cilastatin
• Date of first enrolment: February 5, 2015
• Target sample size: 452
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02321800
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Bulgaria, Croatia, Czech Republic, Czechia, Georgia, Germany, Hungary, Italy, Japan, Latvia, Poland, Romania, Russian Federation, Spain, United States

Contacts

• Name: Shionogi Clinical Trials Administrator Clinical Support Help Line
• Affiliation: Shionogi

Key inclusion & exclusion criteria

Inclusion Criteria:

- Hospitalized male and female patients = 18 years

- Clinical diagnosis of either complicated urinary tract infections (cUTI) with or
without pyelonephritis or acute uncomplicated pyelonephritis

- cUTI diagnosed with a history of = 1 of the following:

- Indwelling urinary catheter or recent instrumentation of the urinary tract

- Urinary retention (caused by benign prostatic hypertrophy)

- Urinary retention of at least 100 mL or more of residual urine after voiding
(neurogenic bladder)

- Obstructive uropathy

- Azotemia caused by intrinsic renal disease (blood urea nitrogen and creatinine
values greater than normal laboratory values) OR Pyelonephritis and normal
urinary tract anatomy, ie, acute uncomplicated pyelonephritis AND

At least 2 of the following signs or symptoms:

- Chills or rigors or warmth associated with fever (temperature greater than or equal to
38 degrees Celsius)

- Flank pain (pyelonephritis) or suprapubic/pelvic pain (cUTI)

- Nausea or vomiting

- Dysuria, urinary frequency, or urinary urgency

- Costo-vertebral angle tenderness on physical examination AND

All subjects had to have urinalysis evidence of pyuria demonstrated by 1 of the following:

- Dipstick analysis positive for leukocyte esterase

- = 10 white blood cells (WBCs) per µL in unspun urine, or = 10 WBCs per high power
field in spun urine

- Positive urine culture within 48 hours prior to randomization containing =10^5
colony forming unit (CFU)/mL of a Gram-negative uropathogen likely to be
susceptible to imipenem (IPM)

- Patients who were treated previously with an empiric antibiotic other than the
study drugs but failed treatment, both clinically and microbiologically, were
eligible for the study if they had an identified Gram-negative uropathogen that
was not susceptible to the previously used empiric treatment and likely to be
susceptible to IPM

- Subjects receiving antibiotic prophylaxis for UTI who present with signs and
symptoms consistent with an active new UTI

Exclusion Criteria:

- Urine culture identifies only a Gram-positive pathogen and/or a Gram-negative
uropathogen resistant to IPM

- Urine culture at study entry isolates more than 2 uropathogens or patient has a
confirmed fungal UTI

- Asymptomatic bacteriuria, the presence of >10^5 CFU/mL of a uropathogen and pyuria but
without local or systemic symptoms

- Patient is receiving hemodialysis or peritoneal dialysis



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Urinary Tract Infections

Intervention(s)

Drug: Cefiderocol

Drug: Imipenem/cilastatin

Primary Outcome(s)

Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Test of Cure [Time Frame: Test of cure (TOC; 7 days after end of treatment [EOT], equivalent to Study Day 14 to 21)]

Secondary Outcome(s)

Number of Participants With Adverse Events [Time Frame: From first dose of study drug until 28 days after end of treatment; Day 35 to 42]

Percentage of Participants With Microbiological Eradication at Follow-up Per Uropathogen [Time Frame: Follow-up, 14 days after the end of treatment, Day 21 to 28]

Percentage of Participants With Clinical Response at Test of Cure [Time Frame: Test of cure, 7 days after end of treatment, Day 14 to 21]

Percentage of Participants With Clinical Response at End of Treatment Per Uropathogen [Time Frame: End of treatment, Day 7 to 14]

Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Follow-up [Time Frame: Follow-up (FUP; 14 days after end of treatment, Day 21 to 28)]

Percentage of Participants With Microbiological Eradication at Early Assessment Per Uropathogen [Time Frame: Early assessment, Day 4]

Percentage of Participants With Microbiological Eradication at End of Treatment Per Uropathogen [Time Frame: End of treatment, Day 7 to 14]

Percentage of Participants With Microbiological Eradication at Test of Cure Per Uropathogen [Time Frame: Test of cure; 7 days after end of treatment, Day 14 to 21]

Urine Concentration of Cefiderocol [Time Frame: Day 3, 2 hours and 6 hours after end of infusion]

Percentage of Participants With Clinical Response at End of Treatment [Time Frame: End of treatment, Day 7 to 14]

Percentage of Participants With Clinical Response at Follow-up [Time Frame: Follow-up, 14 days after end of treatment, Day 21 to 28]

Percentage of Participants With Clinical Response at Test of Cure Per Uropathogen [Time Frame: Test of cure, 7 days after end of treatment, Day 14 to 21]

Percentage of Participants With Clinical Response at Early Assessment Per Uropathogen [Time Frame: Early assessment, Day 4]

Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at End of Treatment [Time Frame: End of treatment (EOT; Day 7 to 14)]

Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Early Assessment [Time Frame: Early assessment (EA; Day 4)]

Percentage of Participants With Microbiological Eradication at End of Treatment [Time Frame: End of treatment, Day 7 to 14]

Plasma Concentration of Cefiderocol [Time Frame: On Day 3 of dosing prior to infusion, end of infusion, and at 1 hour post infusion]

Percentage of Participants With Clinical Response at Early Assessment [Time Frame: Early assessment, Day 4]

Percentage of Participants With Clinical Response at Follow-up Per Uropathogen [Time Frame: Follow-up, 14 days after the end of treatment, Day 21 to 28]

Percentage of Participants With Microbiological Eradication at Follow-up [Time Frame: Follow-up, 14 days after end of treatment, Day 21 to 28]

Percentage of Participants With Microbiological Eradication at Test of Cure [Time Frame: Test of cure (7 days after end of treatment, Day 14 to 21)]

Percentage of Participants With Microbiological Eradication at Early Assessment [Time Frame: Early assessment, Day 4]

Secondary ID(s)

1409R2121

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 12/12/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02321800