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

NCT02959957 | Completed Phase 4

• 2 other identifiers: FoHM/UVI 20152015-003898-15
• Study Type: interventional
• Target: 157
• Locations: 1 country
• Sites: 12

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.

Conditions

Urinary Tract Infections

Outcome Measures

Primary Outcomes (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.

  Superiority analysis.

  Within 12 hours after the last dose of study drug.

Secondary Outcomes (5)

• Number of patients with clinical cure in each treatment group.

  7-10 days after discontinuation of antibiotic treatment (parenteral and oral).

• Number of patients with early clinical response.

  Within 12 hours after the 9th dose of study drug.

• Bacteriological cure per patient and per pathogen measured as negative urine Culture <1000 CFU/ml.

  7-10 days after discontinuation of antibiotic treatment (parenteral and oral).

• Early bacteriological response measured as negative urine Culture <1000 CFU/ml.

  Within 12 hours after the 9th dose of study drug.

• Rate of patients with diarrhea (≥ 3 loose stools per day)

  From the first dose of study drug until 7-10 days after discontinuation of antibiotic treatment (parenteral and oral).

Other Outcomes (1)

• Frequency of adverse events

  From the first dose of study drug until 4-6 weeks after discontinuation of antibiotic treatment (parenteral and per oral).

Study Arms (2)

Temocillin

EXPERIMENTAL

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

Cefotaxime

ACTIVE COMPARATOR

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

Interventions

Temocillin DRUG

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.

Also known as: Negaban

Temocillin

Cefotaxime DRUG

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.

Also known as: Claforan

Cefotaxime

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Håkan Hanberger: lead

Study Sites (12)

Karolinska University Hospital

Solna, Stockholm County, 171 76, Sweden

Location

Helsingborg Hospital

Helsingborg, 251 87, Sweden

Location

Centralsjukhuset Kristianstad

Kristianstad, 291 85, Sweden

Location

Linköping University Hospital

Linköping, 581 85, Sweden

Location

Skåne University Hospital

Lund, 221 85, Sweden

Location

Vrinnevisjukhuset i Norrköping

Norrköping, 601 82, Sweden

Location

Örebro University Hospital

Örebro, 701 85, Sweden

Location

Östersund Hospital

Östersund, 83131, Sweden

Location

Capio S:t Görans hospital

Stockholm, 112 81, Sweden

Location

Sundsvall Hospital

Sundsvall, 856 43, Sweden

Location

University Hospital of Umeå

Umeå, 901 85, Sweden

Location

Västmanlands sjukhus i Västerås

Västerås, 721 89, Sweden

Location

MeSH Terms

Conditions

Urinary Tract Infections

Interventions

temocillin; Cefotaxime

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Håkan Hanberger, Professor

  University Hospital, Linkoeping

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 13, 2016
• First Posted: November 9, 2016
• Study Start: May 20, 2016
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: September 16, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (12)