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

NCT ID: NCT02959957

Last Updated: 2019-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 157 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-20
• Study Completion Date: 2019-08-31

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.

Conditions

Urinary Tract Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Temocillin

Intervention Type: 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.

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.

Group Type: ACTIVE_COMPARATOR

Cefotaxime

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Negaban; Claforan

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Håkan Hanberger

OTHER_GOV

Sponsor Role: lead

Responsible Party

Håkan Hanberger

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Håkan Hanberger, Professor

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Linkoeping

Locations

Karolinska University Hospital

Solna, Stockholm County, Sweden

Helsingborg Hospital

Helsingborg, , Sweden

Centralsjukhuset Kristianstad

Kristianstad, , Sweden

Linköping University Hospital

Linköping, , Sweden

Skåne University Hospital

Lund, , Sweden

Vrinnevisjukhuset i Norrköping

Norrköping, , Sweden

Örebro University Hospital

Örebro, , Sweden

Östersund Hospital

Östersund, , Sweden

Capio S:t Görans hospital

Stockholm, , Sweden

Sundsvall Hospital

Sundsvall, , Sweden

University Hospital of Umeå

Umeå, , Sweden

Västmanlands sjukhus i Västerås

Västerås, , Sweden

Countries

Sweden

Other Identifiers

2015-003898-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FoHM/UVI 2015

Identifier Type: -

Identifier Source: org_study_id