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

Shionogi

Status and phase: Completed; Phase 2

Conditions: Urinary Tract Infections

Treatments: Drug: Imipenem/cilastatin; Drug: Cefiderocol

Study type: Interventional

Funder types: Industry

Identifiers

NCT02321800

1409R2121

Details and patient eligibility

About

The purpose of this study was to determine the efficacy and safety of intravenous cefiderocol (S-649266) in hospitalized adults with complicated urinary tract infections caused by Gram-negative pathogens.

Enrollment: 452 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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452 participants in 2 patient groups

Cefiderocol

Experimental group

Description:

Participants received 2 g cefiderocol by intravenous injection once every 8 hours for 7 to 14 days.

Treatment:

Drug: Cefiderocol

Imipenem/cilastatin

Active Comparator group

Description:

Participants received 1 g each of imipenem/cilastatin by intravenous injection once every 8 hours for 7 to 14 days.

Treatment:

Drug: Imipenem/cilastatin