Urinary Tract InfectionsPhase 2APEKS-cUTINCT02321800
A Study of Efficacy and Safety of Intravenous Cefiderocol (S-649266) Versus Imipenem/Cilastatin in Complicated Urinary Tract Infections
A Phase 2 study testing Cefiderocol and Imipenem/cilastatin in people with Urinary Tract Infections, run by Shionogi.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urinary Tract Infections
- What is being tested?
- Cefiderocol and Imipenem/cilastatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 452 participants
- Where
- No sites listed yet
- Study dates
- 5 Feb 2015to 16 Aug 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 20Show fewer
- 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
Who cannot join
- 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
About this study
Official 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
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.
- Conditions
- Urinary Tract Infections
- Being tested
- Cefiderocol, Imipenem/cilastatin
- Keywords
- S-649266, complicated urinary tract infection, cefiderocol, acute uncomplicated pyelonephritis, Gram-negative pathogens, imipenem/cilastatin
- Medical subject headings
- Urinary Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CefiderocolDrug
Also called FETROJA®, S-649266
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/cilastatinDrug
Also called PRIMAXIN®
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.
| Study group | Role | What they receive |
|---|---|---|
| Cefiderocol | Experimental | Participants received 2 g cefiderocol by intravenous injection once every 8 hours for 7 to 14 days. Receives: Drug: Cefiderocol |
| Imipenem/cilastatin | Active comparator | Participants received 1 g each of imipenem/cilastatin by intravenous injection once every 8 hours for 7 to 14 days. Receives: Drug: Imipenem/cilastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Test of Cure
The primary efficacy endpoint was the composite outcome of clinical response and microbiological response at the test of cure assessment, defined as 7 days (±2 days) after the end of antibiotic treatment.
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms.
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at > 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Measured: Test of cure (TOC; 7 days after end of treatment [EOT], equivalent to Study Day 14 to 21)
Secondary outcomes (22)
Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Early Assessment
A composite outcome of clinical response and microbiological response at the early assessment, defined as Day 4 of antibiotic treatment.
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms.
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at > 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Measured: Early assessment (EA; Day 4)
Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at End of Treatment
A composite outcome of clinical response and microbiological response at the end of treatment, defined as the end of the last infusion of antibiotic treatment.
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms.
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at > 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Measured: End of treatment (EOT; Day 7 to 14)
Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Follow-up
A composite response of clinical response and microbiological response at the follow-up assessment, defined as 14 days after the end of treatment.
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with sustained response defined as all pre-therapy signs and symptoms of cUTI show no evidence of recurrence after administration of the last dose of study drug.
Microbiological outcome was based on quantitative microbiological urine cultures, with sustained eradication defined as a urine culture obtained after documented eradication at the TOC, up to and including the FUP, showed that the bacterial uropathogen(s) identified at baseline at ≥ 10⁵ CFU/mL remained < 10⁴ CFU/mL.
Measured: Follow-up (FUP; 14 days after end of treatment, Day 21 to 28)
Percentage of Participants With Microbiological Eradication at Test of Cure
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as all bacterial uropathogens found at study entry at > 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Measured: Test of cure (7 days after end of treatment, Day 14 to 21)
Percentage of Participants With Microbiological Eradication at Early Assessment
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as all bacterial uropathogens found at study entry at > 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Measured: Early assessment, Day 4
Percentage of Participants With Microbiological Eradication at End of Treatment
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as all bacterial uropathogens found at study entry at > 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Measured: End of treatment, Day 7 to 14
Percentage of Participants With Microbiological Eradication at Follow-up
Microbiological outcome was based on quantitative microbiological urine cultures, with sustained eradication defined as a urine culture obtained after documented eradication at the TOC, up to and including the FUP, where the bacterial uropathogen(s) identified at baseline at ≥ 10⁵ CFU/mL remained < 10⁴ CFU/mL.
Measured: Follow-up, 14 days after end of treatment, Day 21 to 28
Percentage of Participants With Microbiological Eradication at Test of Cure Per Uropathogen
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at > 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Measured: Test of cure; 7 days after end of treatment, Day 14 to 21
Percentage of Participants With Microbiological Eradication at Early Assessment Per Uropathogen
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at > 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Measured: Early assessment, Day 4
Percentage of Participants With Microbiological Eradication at End of Treatment Per Uropathogen
Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at > 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Measured: End of treatment, Day 7 to 14
Percentage of Participants With Microbiological Eradication at Follow-up Per Uropathogen
Microbiological outcome was based on quantitative microbiological urine cultures, with sustained eradication defined as a urine culture obtained after documented eradication at the TOC, up to and including the FUP, where the bacterial uropathogen identified at baseline at ≥ 10⁵ CFU/mL remained < 10⁴ CFU/mL.
Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Measured: Follow-up, 14 days after the end of treatment, Day 21 to 28
Percentage of Participants With Clinical Response at Test of Cure
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms.
Measured: Test of cure, 7 days after end of treatment, Day 14 to 21
Percentage of Participants With Clinical Response at Early Assessment
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms.
Measured: Early assessment, Day 4
Percentage of Participants With Clinical Response at End of Treatment
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms.
Measured: End of treatment, Day 7 to 14
Percentage of Participants With Clinical Response at Follow-up
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with sustained response defined as all pre-therapy signs and symptoms of cUTI showing no evidence of recurrence after administration of the last dose of study drug.
Measured: Follow-up, 14 days after end of treatment, Day 21 to 28
Percentage of Participants With Clinical Response at Test of Cure Per Uropathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Measured: Test of cure, 7 days after end of treatment, Day 14 to 21
Percentage of Participants With Clinical Response at Early Assessment Per Uropathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Measured: Early assessment, Day 4
Percentage of Participants With Clinical Response at End of Treatment Per Uropathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Measured: End of treatment, Day 7 to 14
Percentage of Participants With Clinical Response at Follow-up Per Uropathogen
Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with sustained response defined as all pre-therapy signs and symptoms of cUTI show no evidence of recurrence after administration of the last dose of study drug. Results are reported for the 4 most frequent uropathogens, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis.
Measured: Follow-up, 14 days after the end of treatment, Day 21 to 28
Plasma Concentration of Cefiderocol
Measured: On Day 3 of dosing prior to infusion, end of infusion, and at 1 hour post infusion
Urine Concentration of Cefiderocol
Measured: Day 3, 2 hours and 6 hours after end of infusion
Number of Participants With Adverse Events
A serious adverse event was defined by regulation as any adverse event (AE) occurring at any dose that resulted in any of the following outcomes:
- Death
- Life-threatening condition
- Hospitalization or prolongation of existing hospitalization
- Persistent or significant disability/incapacity
- Congenital anomaly/birth defect
- Other medically important condition.
The relationship of an event to the study drug was determined by the investigator based on whether the AE could be reasonably explained as being caused by the study drug.
Measured: From first dose of study drug until 28 days after end of treatment; Day 35 to 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2014 (estimated)
- Study start5 Feb 2015
- Primary completion26 Jul 2016
- Study completion16 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Urinary Tract InfectionsStudies of the same condition, open and under way.
- More trials run by ShionogiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 452 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shionogi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shionogi Clinical Trials Administrator Clinical Support Help Line, Study director, Shionogi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02321800
- Sponsor's protocol ID
- 1409R2121
- Acronym
- APEKS-cUTI
- Status last verified
- Nov 2019
- First submitted
- 11 Nov 2014
- Last updated
- 12 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Expanded access
- Available
Publications
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.
PubMed 30509675Portsmouth 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.
PubMed 34868583Wenzler 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.
PubMed 34792787Naseer 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.
PubMed 33393598
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02321800
- Acronym / sponsor ID
- APEKS-cUTI / 1409R2121
- Conditions
- Urinary Tract Infections
- Keywords
- S-649266, complicated urinary tract infection, cefiderocol, acute uncomplicated pyelonephritis, Gram-negative pathogens, imipenem/cilastatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 452 participants (actual)
- Lead sponsor
- ShionogiIndustry (pharma, biotech, devices)
- Study start
- 5 Feb 2015 (actual)
- Primary completion
- 26 Jul 2016 (actual)
- Study completion
- 16 Aug 2016 (actual)
- First posted
- 22 Dec 2014 (estimated)
- Results
- Posted 12 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cefiderocol | Experimental | Drug: CefiderocolParticipants received 2 g cefiderocol by intravenous injection once every 8 hours for 7 to 14 days. |
| Imipenem/cilastatin | Active comparator | Drug: Imipenem/cilastatinParticipants received 1 g each of imipenem/cilastatin by intravenous injection once every 8 hours for 7 to 14 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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:
- 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)
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CefiderocolAlso: FETROJA®, S-6492662000 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. | Drug | Cefiderocol |
| Imipenem/cilastatinAlso: PRIMAXIN®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. | Drug | Imipenem/cilastatin |
Primary outcome
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)
The primary efficacy endpoint was the composite outcome of clinical response and microbiological response at the test of cure assessment, defined as 7 days (±2 days) after the end of antibiotic treatment. Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms, with response defined as resolution or improvement of complicated urinary tract infection symptoms present at study entry and the absence of new symptoms. Microbiological outcome was based on quantitative microbiological urine cultures, with eradication defined as the bacterial pathogen found at study entry at > 1 × 10⁵ CFU/mL reduced to 1 × 10⁴ CFU/mL or less.
22 secondary outcomes
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 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 Follow-up
Time frame: Follow-up (FUP; 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
Percentage of Participants With Microbiological Eradication at End of Treatment
Time frame: End of treatment, Day 7 to 14
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 Per Uropathogen
Time frame: Test of cure; 7 days after end of treatment, Day 14 to 21
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 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 Early Assessment
Time frame: Early assessment, Day 4
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 Clinical Response at End of Treatment Per Uropathogen
Time frame: End of treatment, Day 7 to 14
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
Plasma Concentration of Cefiderocol
Time frame: On Day 3 of dosing prior to infusion, end of infusion, and at 1 hour post infusion
Urine Concentration of Cefiderocol
Time frame: Day 3, 2 hours and 6 hours after end of infusion
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30509675Portsmouth 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.
- Derived from this study: PubMed 34868583Portsmouth 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.
- Derived from this study: PubMed 34792787Wenzler 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.
- Derived from this study: PubMed 33393598Naseer 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shionogi Clinical Trials Administrator Clinical Support Help Line study director
Shionogi
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cefiderocol and Imipenem/cilastatin in people with Urinary Tract Infections, run by Shionogi.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02321800, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2019.