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Disturbance of the Intestinal Microbiota by Temocillin vs Cefotaxime in Treatment of Febrile Urinary Tract Infections

Primary Purpose

Urinary Tract Infections

Status
Completed
Phase
Phase 4
Locations
Sweden
Study Type
Interventional
Intervention
Temocillin
Cefotaxime
Sponsored by
Håkan Hanberger
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urinary Tract Infections

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Males and females ≥ 18 years of age with suspected or confirmed febrile UTI, fulfilling at least one of the following signs and symptoms:

    • Flank pain or suprapubic pain, Tenderness over the kidney on physical examination, Urinary symptoms such as dysuria, urinary frequency or urinary urgency
  • Fever ≥ 38.0°C (highest temperature recorded at home or at the hospital)
  • Positive urinalysis tests (U-Nitrit and/or U-LPK)
  • Have a pre-treatment baseline urinary culture obtained
  • Require iv antibacterial treatment of the presumed infection
  • Fertile women: Agree to practice highly effective anti-contraceptive methods from study-start to TOC
  • Signed informed consent

Exclusion Criteria:

  • Have a documented history of hypersensitivity or allergic reaction to any beta-lactam
  • Pregnant or nursing women
  • Receipt of any prior potentially therapeutic antibacterial agent within 1 month before randomisation and sampling for urine and faecal cultures. Exceptions will prior treatment with pivmecillinam or nitrofurantoin.
  • Known chronic renal insufficiency (creatinine clearance < 10 mL/min at screening as estimated by Cockcroft-Gault), or receiving intermittent haemodialysis or peritoneal dialysis
  • Known colonization with ESBL
  • Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the subject or the quality of study data.

Sites / Locations

  • Karolinska University Hospital
  • Helsingborg Hospital
  • Centralsjukhuset Kristianstad
  • Linköping University Hospital
  • Skåne University Hospital
  • Vrinnevisjukhuset i Norrköping
  • Capio S:t Görans hospital
  • Sundsvall Hospital
  • University Hospital of Umeå
  • Västmanlands sjukhus i Västerås
  • Örebro University Hospital
  • Östersund Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Temocillin

Cefotaxime

Arm Description

Temocillin powder for solution för injection/infusion, per day 6 g (2 g three times per day). Treatment length 7-10 days of which at least 3 days administration with the study drug.

Cefotaxime powder for solution för injection/infusion, per day 3-6 g (1-2 g three times per day). Treatment length 7-10 days of which at least 3 days administration with the study drug.

Outcomes

Primary Outcome Measures

Number of patients with emergence of any of the two following events: Colonisation or infection with C. difficile and/or with Enterobacteriaceae resistant to 3rd generation cephalosporins. Measured in cultures from faecal samples.
Superiority analysis.

Secondary Outcome Measures

Number of patients with clinical cure in each treatment group.
Clinical cure defined as patient totally recovered with no remaining symptoms of UTI or no recurrence with symptoms or no need of further treatment against the current infection. Non-inferiority analysis.
Number of patients with early clinical response.
Non-inferiority analysis.
Bacteriological cure per patient and per pathogen measured as negative urine Culture <1000 CFU/ml.
Non-inferiority analysis.
Early bacteriological response measured as negative urine Culture <1000 CFU/ml.
Non-inferiority analysis.
Rate of patients with diarrhea (≥ 3 loose stools per day)

Full Information

First Posted
October 13, 2016
Last Updated
September 12, 2019
Sponsor
Håkan Hanberger
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1. Study Identification

Unique Protocol Identification Number
NCT02959957
Brief Title
Disturbance of the Intestinal Microbiota by Temocillin vs Cefotaxime in Treatment of Febrile Urinary Tract Infections
Official Title
A Randomized, Controlled, Multicentre Trial of Collateral Damage on the Intestinal Microbiota Inferred by Temocillin Versus Cefotaxime in Patients Receiving Empirical Treatment for Febrile Urinary Tract Infections
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
May 20, 2016 (Actual)
Primary Completion Date
August 2019 (Actual)
Study Completion Date
August 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Håkan Hanberger

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will evaluate the ecological impact on the intestinal microbiota and compare the safety and efficacy of temocillin compared to cefotaxime, in empiric treatment of febrile UTI. Half of participants will receive temocillin and the other half will receive cefotaxime.
Detailed Description
Temocillin is a narrow spectrum antibiotic with activity against gram negative bacteria inclusive many ESBL producing bacteria. Temocillin is approved and marketed in a few European countries since the 1980´s but not in Sweden. The aim of the study is to find an ecological favorable alternative to cephalosporins in the treatment of this common indication. The hypothesis is that treatment with temocillin causes less disturbances on the intestinal microbiota while at least comparable efficacy. The study will be performed as an open prospective multicentre study with two parallel groups comparing 2 g temocillin three times daily with 1-2 g cefotaxim three times daily for 7-10 days in male and female adult patients with febrile urinary tract infection.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urinary Tract Infections

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
157 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Temocillin
Arm Type
Experimental
Arm Description
Temocillin powder for solution för injection/infusion, per day 6 g (2 g three times per day). Treatment length 7-10 days of which at least 3 days administration with the study drug.
Arm Title
Cefotaxime
Arm Type
Active Comparator
Arm Description
Cefotaxime powder for solution för injection/infusion, per day 3-6 g (1-2 g three times per day). Treatment length 7-10 days of which at least 3 days administration with the study drug.
Intervention Type
Drug
Intervention Name(s)
Temocillin
Other Intervention Name(s)
Negaban
Intervention Description
Total antibiotic treatment 7-10 days, of which at least 72 hours (9 doses) initial temocillin administration. In case of bacteraemia at baseline the total antibiotic treatment can be extended up to 14 days.
Intervention Type
Drug
Intervention Name(s)
Cefotaxime
Other Intervention Name(s)
Claforan
Intervention Description
Total antibiotic treatment 7-10 days, of which at least 72 hours (9 doses) initial cefotaxime administration. In case of bacteraemia at baseline the total antibiotic treatment can be extended up to 14 days.
Primary Outcome Measure Information:
Title
Number of patients with emergence of any of the two following events: Colonisation or infection with C. difficile and/or with Enterobacteriaceae resistant to 3rd generation cephalosporins. Measured in cultures from faecal samples.
Description
Superiority analysis.
Time Frame
Within 12 hours after the last dose of study drug.
Secondary Outcome Measure Information:
Title
Number of patients with clinical cure in each treatment group.
Description
Clinical cure defined as patient totally recovered with no remaining symptoms of UTI or no recurrence with symptoms or no need of further treatment against the current infection. Non-inferiority analysis.
Time Frame
7-10 days after discontinuation of antibiotic treatment (parenteral and oral).
Title
Number of patients with early clinical response.
Description
Non-inferiority analysis.
Time Frame
Within 12 hours after the 9th dose of study drug.
Title
Bacteriological cure per patient and per pathogen measured as negative urine Culture <1000 CFU/ml.
Description
Non-inferiority analysis.
Time Frame
7-10 days after discontinuation of antibiotic treatment (parenteral and oral).
Title
Early bacteriological response measured as negative urine Culture <1000 CFU/ml.
Description
Non-inferiority analysis.
Time Frame
Within 12 hours after the 9th dose of study drug.
Title
Rate of patients with diarrhea (≥ 3 loose stools per day)
Time Frame
From the first dose of study drug until 7-10 days after discontinuation of antibiotic treatment (parenteral and oral).
Other Pre-specified Outcome Measures:
Title
Frequency of adverse events
Time Frame
From the first dose of study drug until 4-6 weeks after discontinuation of antibiotic treatment (parenteral and per oral).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males and females ≥ 18 years of age with suspected or confirmed febrile UTI, fulfilling at least one of the following signs and symptoms: Flank pain or suprapubic pain, Tenderness over the kidney on physical examination, Urinary symptoms such as dysuria, urinary frequency or urinary urgency Fever ≥ 38.0°C (highest temperature recorded at home or at the hospital) Positive urinalysis tests (U-Nitrit and/or U-LPK) Have a pre-treatment baseline urinary culture obtained Require iv antibacterial treatment of the presumed infection Fertile women: Agree to practice highly effective anti-contraceptive methods from study-start to TOC Signed informed consent Exclusion Criteria: Have a documented history of hypersensitivity or allergic reaction to any beta-lactam Pregnant or nursing women Receipt of any prior potentially therapeutic antibacterial agent within 1 month before randomisation and sampling for urine and faecal cultures. Exceptions will prior treatment with pivmecillinam or nitrofurantoin. Known chronic renal insufficiency (creatinine clearance < 10 mL/min at screening as estimated by Cockcroft-Gault), or receiving intermittent haemodialysis or peritoneal dialysis Known colonization with ESBL Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the subject or the quality of study data.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Håkan Hanberger, Professor
Organizational Affiliation
University Hospital, Linkoeping
Official's Role
Principal Investigator
Facility Information:
Facility Name
Karolinska University Hospital
City
Solna
State/Province
Stockholm
ZIP/Postal Code
171 76
Country
Sweden
Facility Name
Helsingborg Hospital
City
Helsingborg
ZIP/Postal Code
251 87
Country
Sweden
Facility Name
Centralsjukhuset Kristianstad
City
Kristianstad
ZIP/Postal Code
291 85
Country
Sweden
Facility Name
Linköping University Hospital
City
Linköping
ZIP/Postal Code
581 85
Country
Sweden
Facility Name
Skåne University Hospital
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Facility Name
Vrinnevisjukhuset i Norrköping
City
Norrköping
ZIP/Postal Code
601 82
Country
Sweden
Facility Name
Capio S:t Görans hospital
City
Stockholm
ZIP/Postal Code
112 81
Country
Sweden
Facility Name
Sundsvall Hospital
City
Sundsvall
ZIP/Postal Code
856 43
Country
Sweden
Facility Name
University Hospital of Umeå
City
Umeå
ZIP/Postal Code
901 85
Country
Sweden
Facility Name
Västmanlands sjukhus i Västerås
City
Västerås
ZIP/Postal Code
721 89
Country
Sweden
Facility Name
Örebro University Hospital
City
Örebro
ZIP/Postal Code
701 85
Country
Sweden
Facility Name
Östersund Hospital
City
Östersund
ZIP/Postal Code
83131
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
No

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Disturbance of the Intestinal Microbiota by Temocillin vs Cefotaxime in Treatment of Febrile Urinary Tract Infections

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