Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02959957
Recruitment Status : Recruiting
First Posted : November 9, 2016
Last Update Posted : June 18, 2018
Sponsor:
Information provided by (Responsible Party):
Håkan Hanberger, Public Health Agency of Sweden

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.

Condition or disease Intervention/treatment Phase
Urinary Tract Infections Drug: Temocillin Drug: Cefotaxime Phase 4

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 332 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 2016
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Cefotaxime

Arm Intervention/treatment
Experimental: Temocillin
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.
Drug: Temocillin
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.
Other Name: Negaban

Active Comparator: Cefotaxime
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.
Drug: Cefotaxime
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.
Other Name: Claforan




Primary Outcome Measures :
  1. 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. [ Time Frame: Within 12 hours after the last dose of study drug. ]
    Superiority analysis.


Secondary Outcome Measures :
  1. Number of patients with clinical cure in each treatment group. [ Time Frame: 7-10 days after discontinuation of antibiotic treatment (parenteral and oral). ]
    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.

  2. Number of patients with early clinical response. [ Time Frame: Within 12 hours after the 9th dose of study drug. ]
    Non-inferiority analysis.

  3. Bacteriological cure per patient and per pathogen measured as negative urine Culture <1000 CFU/ml. [ Time Frame: 7-10 days after discontinuation of antibiotic treatment (parenteral and oral). ]
    Non-inferiority analysis.

  4. Early bacteriological response measured as negative urine Culture <1000 CFU/ml. [ Time Frame: Within 12 hours after the 9th dose of study drug. ]
    Non-inferiority analysis.

  5. 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 Outcome Measures:
  1. 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). ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02959957


Contacts
Layout table for location contacts
Contact: Charlotta Edlund, Professor +46102052011 charlotta.edlund@folkhalsomyndigheten.se
Contact: Gunilla Skoog, M. Sci. Ph. +46102052406 gunilla.skoog@folkhalsomyndigheten.se

Locations
Layout table for location information
Sweden
Danderyd University Hospital Recruiting
Danderyd, Stockholm, Sweden, 182 88
Contact: Jesper Ericsson       jesper.ericsson@ds.se   
Karolinska University Hospital Recruiting
Solna, Stockholm, Sweden, 171 76
Contact: Anders Ternhag       anders.ternhag@karolinska.se   
Sahlgrenska University Hospital Recruiting
Göteborg, Sweden, 416 50
Contact: Daniel Bremell       daniel.bremell@infect.gu.se   
Helsingborg Hospital Recruiting
Helsingborg, Sweden, 251 87
Contact: Anna-Karin Lindgren       Anna-Karin.A.Lindgren@skane.se   
Linköping University Hospital Recruiting
Linköping, Sweden, 581 85
Contact: Åse Östholm Balkhed       ase.ostholm.balkhed@lio.se   
Skåne University Hospital Recruiting
Lund, Sweden, 221 85
Contact: Gisela Otto       gisela.otto@skane.se   
Capio S:t Görans hospital Recruiting
Stockholm, Sweden, 112 81
Contact: Daniel Holmström       daniel.holmstrom@capiostgoran.se   
Sundsvall Hospital Recruiting
Sundsvall, Sweden, 856 43
Contact: Maria Tempé       maria.tempe@lvn.se   
University Hospital of Umeå Recruiting
Umeå, Sweden, 901 85
Contact: Maria Furberg       maria.furberg@umu.se   
Örebro University Hospital Recruiting
Örebro, Sweden, 701 85
Contact: Simon Athlin       simon.athlin@regionorebrolan.se   
Östersund Hospital Recruiting
Östersund, Sweden, 83131
Contact: Elin Hedman       elin.hedman@regionjh.se   
Sponsors and Collaborators
Håkan Hanberger
Investigators
Layout table for investigator information
Principal Investigator: Håkan Hanberger, Professor University Hospital, Linkoeping

Layout table for additonal information
Responsible Party: Håkan Hanberger, Professor, Public Health Agency of Sweden
ClinicalTrials.gov Identifier: NCT02959957     History of Changes
Other Study ID Numbers: FoHM/UVI 2015
2015-003898-15 ( EudraCT Number )
First Posted: November 9, 2016    Key Record Dates
Last Update Posted: June 18, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Communicable Diseases
Urinary Tract Infections
Urologic Diseases
Cefotaxime
Cefoxitin
Temocillin
Penicillins
Anti-Bacterial Agents
Anti-Infective Agents