A Study of Efficacy and Safety of Intravenous Cefiderocol (S-649266) Versus Imipenem/Cilastatin in Complicated Urinary Tract Infections
NCT ID: NCT02321800
Last Updated: 2019-12-12
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
452 participants
INTERVENTIONAL
2015-02-05
2016-08-16
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Cefiderocol
Participants received 2 g cefiderocol by intravenous injection once every 8 hours for 7 to 14 days.
Cefiderocol
2000 mg intravenously every 8 hours for 7 to 14 days; dose adjustments for participants with reduced renal function (estimated CrCl ≤ 70 mL/minute) and/or body weight (\< 70 kg) included every 6-hour dosing intervals and/or reduced doses.
Imipenem/cilastatin
Participants received 1 g each of imipenem/cilastatin by intravenous injection once every 8 hours for 7 to 14 days.
Imipenem/cilastatin
1000 mg of each intravenously every 8 hours for 7 to 14 days; dose adjustments for participants with reduced renal function (estimated CrCl ≤ 70 mL/minute) and/or body weight (\< 70 kg) included every 6-hour dosing intervals and/or reduced doses.
Interventions
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Cefiderocol
2000 mg intravenously every 8 hours for 7 to 14 days; dose adjustments for participants with reduced renal function (estimated CrCl ≤ 70 mL/minute) and/or body weight (\< 70 kg) included every 6-hour dosing intervals and/or reduced doses.
Imipenem/cilastatin
1000 mg of each intravenously every 8 hours for 7 to 14 days; dose adjustments for participants with reduced renal function (estimated CrCl ≤ 70 mL/minute) and/or body weight (\< 70 kg) included every 6-hour dosing intervals and/or reduced doses.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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 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
18 Years
ALL
No
Sponsors
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Shionogi
INDUSTRY
Responsible Party
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Principal Investigators
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Shionogi Clinical Trials Administrator Clinical Support Help Line
Role: STUDY_DIRECTOR
Shionogi
Countries
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References
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Portsmouth S, van Veenhuyzen D, Echols R, Machida M, Ferreira JCA, Ariyasu M, Tenke P, Nagata TD. Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2018 Dec;18(12):1319-1328. doi: 10.1016/S1473-3099(18)30554-1. Epub 2018 Oct 25.
Portsmouth S, Echols R, Toyoizumi K, Tillotson G, Nagata TD. Structured patient interview to assess clinical outcomes in complicated urinary tract infections in the APEKS-cUTI study: pilot investigation. Ther Adv Infect Dis. 2021 Nov 24;8:20499361211058257. doi: 10.1177/20499361211058257. eCollection 2021 Jan-Dec.
Wenzler E, Butler D, Tan X, Katsube T, Wajima T. Pharmacokinetics, Pharmacodynamics, and Dose Optimization of Cefiderocol during Continuous Renal Replacement Therapy. Clin Pharmacokinet. 2022 Apr;61(4):539-552. doi: 10.1007/s40262-021-01086-y. Epub 2021 Nov 18.
Naseer S, Weinstein EA, Rubin DB, Suvarna K, Wei X, Higgins K, Goodwin A, Jang SH, Iarikov D, Farley J, Nambiar S. US Food and Drug Administration (FDA): Benefit-Risk Considerations for Cefiderocol (Fetroja(R)). Clin Infect Dis. 2021 Jun 15;72(12):e1103-e1111. doi: 10.1093/cid/ciaa1799.
Other Identifiers
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1409R2121
Identifier Type: -
Identifier Source: org_study_id