Back to resultsAn Efficacy and Safety of Flomoxef Versus Cefepime in the Treatment of Participants With Urinary Tract Infections (FLORUS)
Primary Purpose
Urinary Tract Infection
Status
Terminated
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
Flomoxef
Cefepime
Sponsored by
About this trial
This is an interventional treatment trial for Urinary Tract Infection focused on measuring Drug Therapy
Eligibility Criteria
Inclusion Criteria:
- Is a man or woman aged 18 to 70 years, inclusive.
- Has pyuria (a white blood cell [WBC] count greater than 10/μL in unspun urine or greater than or equal to 10 per high power field in spun urine).
- Has clinical signs and/or symptoms of a complicated lower urinary tract infection (UTI) and/or acute pyelonephritis that include one or more of the following: fever (i.e, axillary temperature greater than 37.7°C), chills, malaise, flank pain, back pain, and/or costo-vertebral angle pain or tenderness and/or any symptoms of dysuria (dysuria, urinary urgency, urinary frequency, suprapubic discomfort, new urinary incontinence or worsening of pre-existing incontinence) that occur in the presence of a functional or anatomical abnormality of the urinary tract or in the presence of catheterization.
- Has a pretreatment baseline urine culture specimen obtained within 24 hours before the administration of the first dose of study drug (NOTE: Participants may be enrolled in this study and start intravenous (IV) study drug therapy before the Investigator knows the results of the baseline urine culture).
- Requires IV antibacterial therapy for the treatment of the presumed complicated UTI (cUTI).
- In the opinion of the investigator, is capable of understanding and complying with protocol requirements.
- Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures, or has a legally acceptable representative sign the forms.
- Meets protocol-specified criteria regarding the use of contraception; and 9-Is willing and able to comply with study procedures.
Exclusion Criteria:
- Has received any investigational compound within 30 days of screening.
- Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, or sibling) or may consent under duress.
- Is a female participant who is pregnant or lactating or intending to become pregnant before, during, or within one month after participating in this study, or intends to donate ova during such time period.
- Is a male participant who intends to donate sperm during the course of this study or for 12 weeks thereafter.
- Has participated in another clinical study within the past 30 days.
- Has a history of allergy to or intolerance of beta-lactams (penicillins, cephalosporins or carbopenems).
- Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise: 1) the safety or well-being of the participant or study staff, 2) the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding), or 3) the analysis of results.
- Has received any amount of potentially therapeutic antibacterial therapy after collection of the pretreatment baseline urine culture and before administration of the first dose of study drug.
- Has received any dose of a potentially therapeutic antibacterial agent for the treatment of the current UTI within 48 hours before providing the pretreatment baseline urine culture specimen.
- Has a current urinary catheter that is not scheduled to be removed before the End-of-Therapy (EOT) visit (intermittent straight catheterization during the IV study drug administration period is acceptable).
- Has any history of trauma to the pelvis or urinary tract within one year before the screening visit.
- Has any other contraindications to the medicines that are to be used in the study (according to the manufacturer's instructions).
- Is considered unlikely to survive the four-week study period or has any rapidly progressing disease or immediately life-threatening illness (including acute hepatic failure, respiratory failure or septic shock).
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Flomoxef
Cefepime
Arm Description
Flomoxef, 2g, injection, intravenously, twice daily (every 12 hours), for up to 12 days.
Cefepime, 1g, injection, intravenously, twice daily (every 12 hours) for up to 14 days.
Outcomes
Primary Outcome Measures
Percentage of Participants Who Achieved Resolution of All Clinical Symptoms of a Complicated Urinary Tract Infection (cUTI) at the End of Treatment (EOT) Visit
At the EOT visit (Days 7 to 14), the Investigator collected information about each symptom and performed a judgement about the participant's status. Clinical symptoms present at trial entry were considered to be resolved if the participant has no pyuria; no fever; no malaise, flank pain, back pain, and/or costo-vertebral angle pain or tenderness; and no symptoms of dysuria, urinary urgency, urinary frequency, suprapubic discomfort, new urinary incontinence, or worsening of pre-existing incontinence. Resolution of all clinical symptoms of cUTI were assessed relative to baseline.
Secondary Outcome Measures
Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits
A urine sample was collected at EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine level of uropathogen. Cultures of urine sample were processed by calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10^4 colony forming units per milliliter (CFU/mL). Microbiological success was defined as bacterial uropathogen level of <10^4 CFU/mL. Microbiological response was categorized as:microbiological eradication/persistence/new infection/superinfection. An infection was eradicated if all uropathogens isolated at study entry at a level ≥10^4 CFU/mL have decreased to <10^4 CFU/mL, persistent if level of uropathogen has increased by ≥10^4 CFU/Ml. A new infection, if there is isolation and growth of a uropathogen other than original pathogen and superinfection if there is growth of a uropathogen other than original pathogen at a level ≥10^4 CFU/mL. Microbiological success was assessed relative to baseline.
Percentage of Participants Who Achieved Clinical Resolution of Symptoms of a cUTI at Visit 3, TOC and Late Follow-up (LFU) Visits
At Visit 3 (Day 3) and at the TOC (Days 14 to 21) and LFU visits (Day 30), the Investigator collected information about each symptom and performed a judgement about the participant's status. Clinical symptoms present at trial entry were considered to be resolved if the participant has no pyuria; no fever; no malaise, flank pain, back pain, and/or costo-vertebral angle pain or tenderness; and no symptoms of dysuria, urinary urgency, urinary frequency, suprapubic discomfort, new urinary incontinence, or worsening of pre-existing incontinence. Resolution of all clinical symptoms of cUTI were assessed relative to baseline.
Percentage of Participants With Microbiologic Eradication of the Unique Pathogen at the EOT and TOC Visits
A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Day 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample were processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10^4 CFU/mL. Microbiological response at the TOC visit was based on the same grades as for the EOT visit. The infection was considered to be eradicated if all uropathogens isolated at study entry at a level equal to or greater than 10^4 CFU/mL have decreased to less than 10^4 CFU/mL.
Percentage of Participants With Microbiologic Persistence of the Unique Pathogen at the EOT and TOC Visits
A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample was processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10^4 CFU/mL. Microbiological response at the TOC visit was be based on the same grades as for the EOT visit. The infection was considered to be persistent if the level of the uropathogen has increased by greater than or equal to 10^4 CFU/mL from the time of study entry to that of the EOT and TOC visits.
Percentage of Participants With a New Infection at the EOT and TOC Visits
A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample were processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10^4 CFU/mL. A new infection was defined as the isolation and growth of a uropathogen other than the original pathogen.
Percentage of Participants With a Superinfection at the EOT and TOC Visits
A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample were processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10^4 CFU/mL. A superinfection was defined as growth of a uropathogen other than the original pathogen at a level greater than or equal to 10^4 CFU/mL at any time during the course of active therapy.
Number of Participants With Serious Adverse Events (SAEs) and Treatment-Emergent-Adverse Events (TEAEs)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Number of Participants With Clinically Significant Abnormal Laboratory Values
The number of participants with any markedly abnormal (above or below normal ranges) standard safety laboratory values was collected throughout study.
Number of Participants With Clinically Significant Change in Vital Signs
Vital signs included body temperature (axillary measurement), diastolic and systolic blood pressure (5 minutes), respiratory rate, and pulse (bpm).
Number of Participants With Clinically Significant Change in Physical Examination Findings
Physical examination consists of examinations of the following body systems: (1) cardiovascular system; (2) dermatologic system (3) ears, nose, throat; (4) extremities; (5) eyes; (6) gastrointestinal system; (7) genitourinary system; (8) lymph nodes; (9) musculoskeletal system; (10) nervous system; (11) respiratory system.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02302092
Brief Title
An Efficacy and Safety of Flomoxef Versus Cefepime in the Treatment of Participants With Urinary Tract Infections
Acronym
FLORUS
Official Title
A Phase 3, Randomized, Double-blind, Multicenter Study Comparing the Efficacy and Safety of Intravenous Infusions of Flomoxef Versus Intravenous Infusions of Cefepime in the Treatment of Subjects With Complicated Urinary Tract Infections Including Pyelonephritis
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Terminated
Why Stopped
Study was prematurely terminated due to administrative and strategic reasons
Study Start Date
December 1, 2015 (Actual)
Primary Completion Date
February 2, 2016 (Actual)
Study Completion Date
December 15, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to compare the effectiveness of antibiotic flomoxef with cefepime for the treatment of complicated urinary tract infections (cUTIs) in Russian adults.
Detailed Description
The drug being tested in this study is called Flomoxef. Flomoxef is being tested in people with a complicated urinary tract infection (cUTI) including a kidney infection. This study compares Flomoxef to Cefepime, another antibiotic.
The study enrolled 13 patients.
Participants are randomly assigned by a computer generated number to one of two treatment groups:
Flomoxef - intravenous infusion 2g twice daily (every 12 hours); or
Cefepime - intravenous infusion 1g twice daily (every 12 hours).
This multi-center trial is conducted at 4 sites in the Russian Federation. The overall time to participate in this study is 30+/-3 days. Participants make six visits to the clinic.
Study was prematurely terminated due to administrative and strategic reasons.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urinary Tract Infection
Keywords
Drug Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Flomoxef
Arm Type
Experimental
Arm Description
Flomoxef, 2g, injection, intravenously, twice daily (every 12 hours), for up to 12 days.
Arm Title
Cefepime
Arm Type
Active Comparator
Arm Description
Cefepime, 1g, injection, intravenously, twice daily (every 12 hours) for up to 14 days.
Intervention Type
Drug
Intervention Name(s)
Flomoxef
Intervention Description
Flomoxef intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Cefepime
Other Intervention Name(s)
Maxipime
Intervention Description
Cefepime intravenous infusion
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieved Resolution of All Clinical Symptoms of a Complicated Urinary Tract Infection (cUTI) at the End of Treatment (EOT) Visit
Description
At the EOT visit (Days 7 to 14), the Investigator collected information about each symptom and performed a judgement about the participant's status. Clinical symptoms present at trial entry were considered to be resolved if the participant has no pyuria; no fever; no malaise, flank pain, back pain, and/or costo-vertebral angle pain or tenderness; and no symptoms of dysuria, urinary urgency, urinary frequency, suprapubic discomfort, new urinary incontinence, or worsening of pre-existing incontinence. Resolution of all clinical symptoms of cUTI were assessed relative to baseline.
Time Frame
Baseline and Days 7 to 14
Secondary Outcome Measure Information:
Title
Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits
Description
A urine sample was collected at EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine level of uropathogen. Cultures of urine sample were processed by calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10^4 colony forming units per milliliter (CFU/mL). Microbiological success was defined as bacterial uropathogen level of <10^4 CFU/mL. Microbiological response was categorized as:microbiological eradication/persistence/new infection/superinfection. An infection was eradicated if all uropathogens isolated at study entry at a level ≥10^4 CFU/mL have decreased to <10^4 CFU/mL, persistent if level of uropathogen has increased by ≥10^4 CFU/Ml. A new infection, if there is isolation and growth of a uropathogen other than original pathogen and superinfection if there is growth of a uropathogen other than original pathogen at a level ≥10^4 CFU/mL. Microbiological success was assessed relative to baseline.
Time Frame
Baseline, Days 7 to 14 and 14 to 21
Title
Percentage of Participants Who Achieved Clinical Resolution of Symptoms of a cUTI at Visit 3, TOC and Late Follow-up (LFU) Visits
Description
At Visit 3 (Day 3) and at the TOC (Days 14 to 21) and LFU visits (Day 30), the Investigator collected information about each symptom and performed a judgement about the participant's status. Clinical symptoms present at trial entry were considered to be resolved if the participant has no pyuria; no fever; no malaise, flank pain, back pain, and/or costo-vertebral angle pain or tenderness; and no symptoms of dysuria, urinary urgency, urinary frequency, suprapubic discomfort, new urinary incontinence, or worsening of pre-existing incontinence. Resolution of all clinical symptoms of cUTI were assessed relative to baseline.
Time Frame
Baseline, Days 3, 14 to 21 and 30
Title
Percentage of Participants With Microbiologic Eradication of the Unique Pathogen at the EOT and TOC Visits
Description
A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Day 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample were processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10^4 CFU/mL. Microbiological response at the TOC visit was based on the same grades as for the EOT visit. The infection was considered to be eradicated if all uropathogens isolated at study entry at a level equal to or greater than 10^4 CFU/mL have decreased to less than 10^4 CFU/mL.
Time Frame
Baseline, Days 7 to 14 and 14 to 21
Title
Percentage of Participants With Microbiologic Persistence of the Unique Pathogen at the EOT and TOC Visits
Description
A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample was processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10^4 CFU/mL. Microbiological response at the TOC visit was be based on the same grades as for the EOT visit. The infection was considered to be persistent if the level of the uropathogen has increased by greater than or equal to 10^4 CFU/mL from the time of study entry to that of the EOT and TOC visits.
Time Frame
Baseline, Days 7 to 14 and 14 to 21
Title
Percentage of Participants With a New Infection at the EOT and TOC Visits
Description
A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample were processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10^4 CFU/mL. A new infection was defined as the isolation and growth of a uropathogen other than the original pathogen.
Time Frame
Baseline, Days 7 to 14 and 14 to 21
Title
Percentage of Participants With a Superinfection at the EOT and TOC Visits
Description
A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample were processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10^4 CFU/mL. A superinfection was defined as growth of a uropathogen other than the original pathogen at a level greater than or equal to 10^4 CFU/mL at any time during the course of active therapy.
Time Frame
Baseline, Day 7 to 14 and 14 to 21
Title
Number of Participants With Serious Adverse Events (SAEs) and Treatment-Emergent-Adverse Events (TEAEs)
Description
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Time Frame
Baseline up to Day 30
Title
Number of Participants With Clinically Significant Abnormal Laboratory Values
Description
The number of participants with any markedly abnormal (above or below normal ranges) standard safety laboratory values was collected throughout study.
Time Frame
Day 21
Title
Number of Participants With Clinically Significant Change in Vital Signs
Description
Vital signs included body temperature (axillary measurement), diastolic and systolic blood pressure (5 minutes), respiratory rate, and pulse (bpm).
Time Frame
Day 1 up to Day 21
Title
Number of Participants With Clinically Significant Change in Physical Examination Findings
Description
Physical examination consists of examinations of the following body systems: (1) cardiovascular system; (2) dermatologic system (3) ears, nose, throat; (4) extremities; (5) eyes; (6) gastrointestinal system; (7) genitourinary system; (8) lymph nodes; (9) musculoskeletal system; (10) nervous system; (11) respiratory system.
Time Frame
Day 1 up to Day 21
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Is a man or woman aged 18 to 70 years, inclusive.
Has pyuria (a white blood cell [WBC] count greater than 10/μL in unspun urine or greater than or equal to 10 per high power field in spun urine).
Has clinical signs and/or symptoms of a complicated lower urinary tract infection (UTI) and/or acute pyelonephritis that include one or more of the following: fever (i.e, axillary temperature greater than 37.7°C), chills, malaise, flank pain, back pain, and/or costo-vertebral angle pain or tenderness and/or any symptoms of dysuria (dysuria, urinary urgency, urinary frequency, suprapubic discomfort, new urinary incontinence or worsening of pre-existing incontinence) that occur in the presence of a functional or anatomical abnormality of the urinary tract or in the presence of catheterization.
Has a pretreatment baseline urine culture specimen obtained within 24 hours before the administration of the first dose of study drug (NOTE: Participants may be enrolled in this study and start intravenous (IV) study drug therapy before the Investigator knows the results of the baseline urine culture).
Requires IV antibacterial therapy for the treatment of the presumed complicated UTI (cUTI).
In the opinion of the investigator, is capable of understanding and complying with protocol requirements.
Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures, or has a legally acceptable representative sign the forms.
Meets protocol-specified criteria regarding the use of contraception; and 9-Is willing and able to comply with study procedures.
Exclusion Criteria:
Has received any investigational compound within 30 days of screening.
Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, or sibling) or may consent under duress.
Is a female participant who is pregnant or lactating or intending to become pregnant before, during, or within one month after participating in this study, or intends to donate ova during such time period.
Is a male participant who intends to donate sperm during the course of this study or for 12 weeks thereafter.
Has participated in another clinical study within the past 30 days.
Has a history of allergy to or intolerance of beta-lactams (penicillins, cephalosporins or carbopenems).
Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise: 1) the safety or well-being of the participant or study staff, 2) the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding), or 3) the analysis of results.
Has received any amount of potentially therapeutic antibacterial therapy after collection of the pretreatment baseline urine culture and before administration of the first dose of study drug.
Has received any dose of a potentially therapeutic antibacterial agent for the treatment of the current UTI within 48 hours before providing the pretreatment baseline urine culture specimen.
Has a current urinary catheter that is not scheduled to be removed before the End-of-Therapy (EOT) visit (intermittent straight catheterization during the IV study drug administration period is acceptable).
Has any history of trauma to the pelvis or urinary tract within one year before the screening visit.
Has any other contraindications to the medicines that are to be used in the study (according to the manufacturer's instructions).
Is considered unlikely to survive the four-week study period or has any rapidly progressing disease or immediately life-threatening illness (including acute hepatic failure, respiratory failure or septic shock).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director Clinical Science
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
City
Moscow
Country
Russian Federation
City
Rostov-on-Don
Country
Russian Federation
City
Saint Petersburg
Country
Russian Federation
City
Volgograd
Country
Russian Federation
City
Yaroslavl
Country
Russian Federation
12. IPD Sharing Statement
Learn more about this trial
An Efficacy and Safety of Flomoxef Versus Cefepime in the Treatment of Participants With Urinary Tract Infections
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