Febrile Urinary Tract Infection Randomized Short Treatment Trial (FUTIRST)

Relevance of Biomarkers and Clinical Predictors of Outcome in Unselected Population With Febrile Urinary Tract Infection at Primary Care and Emergency Department in a Prospective, Randomized Cohort Trial Comparing Short (7 Days) Antibiotic Treatment With Conventional Treatment (14 Days)

The purpose of this study is to determine whether a 7-day duration of antibiotic treatment of febrile urinary tract infection (FUTI) is non inferior to 14-day standard duration of treatment in unselected population presenting at primary care or emergency department.

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infection
• Intervention / Treatment: Drug: short treatment (ciprofloxacin)

Detailed Description

In the last decades hospitalization rates of patients with acute pyelonephritis (AP) or FUTI has decreased from almost 100% to 10-30%. The outpatient management of patients with FUTI has become popular as well as oral antimicrobial treatment regiments and shortening of treatment duration. However, as such approaches are only discovered in otherwise young health non-pregnant women, the best management of FUTI in the elderly, men and patients with co-morbidity remains elusive. Bases on personal perception of the attending physician antibiotic treatment, duration varies approximately between 7-14 days. Facing the aging of the general population, it is urgent to better define the optimal treatment for AP or FUTI in an unselected population and to identify those at risk for treatment failure or poor outcome to guide and optimize individual patient management and to prevent on the one hand unnecessary long treatment duration and hospital admission and on the other hand unsafe short duration or unsafe outpatient management.

In this study the efficacy and safety of a 7-day antimicrobial regimen compared to a 14-day antimicrobial regimen will be evaluated in an unselected population presenting with FUTI at primary care or emergency department. In addition a clinical and/or biomarker based scoring system of disease severity will be derived to predict those at risk for treatment failure or poor outcome.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Den Haag, Netherlands, 2501 CK
    • Medical Center Haaglanden
  • Den Haag, Netherlands, 2509 JH
    • Bronovo Hospital
  • Gouda, Netherlands, 2800 BB
    • Groene Hart Hospital
  • Leiden, Netherlands, 2300 RC
    • Leiden University Medical Center
  • Leiden, Netherlands, 2334 CK
    • Alrijne Hospital
  • Leiderdorp, Netherlands, 2350 CC
    • Alrijne Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Competent patient aged 18 years or above
• One or more symptom(s) suggestive of urinary tract infection (dysuria, frequency or urgency*; perineal or suprapubic pain; costo-vertebral tenderness or flank pain)
• Fever (ear or rectal temp of 38.2 oC or higher, or axillary temp of 38 oC or higher), or history of feeling feverish with shivering or rigors in the past 24 hours
• Positive urine nitrate test and/or leucocyturia as depicted by positive leukocyte esterase test or microscopy

Exclusion Criteria:

• Known allergy to fluoroquinolones
• Female patients who are pregnant or lactating
• Patients with known polycystic kidney disease
• Patients on permanent renal replacement therapy (hemodialysis or peritoneal dialysis)
• Patients with history of kidney transplantation
• Residence outside country of enrolment
• Inability to speak or read Dutch
• Isolated causal uropathogen resistant to ciprofloxacin
• Renal abscess
• Chronic bacterial prostatitis
• Suspicion or evidence of any metastatic infectious foci

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Short treatment; 7 days of standard antibiotic treatment (preferably ciprofloxacin) followed by 7 days of placebo	Drug: short treatment (ciprofloxacin); 7 days of antibiotic treatment for febrile urinary tract infection / acute pyelonephritis compared to standard treatment of 14 days
Active Comparator: Standard treatment; 14 days of standard antibiotic treatment (initial b-lactam or fluoroquinolone followed by ciprofloxacin through the 8th till 14th day)	Drug: short treatment (ciprofloxacin); 7 days of antibiotic treatment for febrile urinary tract infection / acute pyelonephritis compared to standard treatment of 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinical cure rate through the 10- to 18-day posttherapy visit. Clinical cure is defined as the resolution of fever and signs and symptoms of UTI.	10-18 day posttherapy

Secondary Outcome Measures

Outcome Measure	Time Frame
Microbiological cure rate 10- to 18-day posttherapy	10-18 day posttherapy
All cause mortality	30 and 90 days
Clinical cure rate 70- to 84- day posttherapy	70-84 days posttherapy
Relapse rate of any urinary tract infection	90 days
Adverse events	90 days
Rate of pelvic floor dysfunction as assessed by standardized questionaire	10-18 days posttherapy
Occurence of Clostridium Difficile associated diarrhea	90 days

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Medical Center Haaglanden; Rijnland Hospital; Groene Hart Ziekenhuis; Spaarne Gasthuis; Bronovo Hospital; Diaconessenhuis Leiden
• Investigators: Study Chair: Jaap T. van Dissel, MD, PhD, Leiden University Medical Center; Principal Investigator: Cees van Nieuwkoop, MD, PhD, Leiden University Medical Center and Haga Hospital

Publications and helpful links

General Publications

• van Nieuwkoop C, van't Wout JW, Assendelft WJ, Elzevier HW, Leyten EM, Koster T, Wattel-Louis GH, Delfos NM, Ablij HC, Kuijper EJ, Pander J, Blom JW, Spelt IC, van Dissel JT. Treatment duration of febrile urinary tract infection (FUTIRST trial): a randomized placebo-controlled multicenter trial comparing short (7 days) antibiotic treatment with conventional treatment (14 days). BMC Infect Dis. 2009 Aug 19;9:131. doi: 10.1186/1471-2334-9-131.
• Stalenhoef JE, van Nieuwkoop C, Wilson DC, van der Starre WE, van der Reijden TJK, Delfos NM, Leyten EMS, Koster T, Ablij HC, van 't Wout JJW, van Dissel JT. Procalcitonin, mid-regional proadrenomedullin and C-reactive protein in predicting treatment outcome in community-acquired febrile urinary tract infection. BMC Infect Dis. 2019 Feb 14;19(1):161. doi: 10.1186/s12879-019-3789-6.
• van Nieuwkoop C, van der Starre WE, Stalenhoef JE, van Aartrijk AM, van der Reijden TJ, Vollaard AM, Delfos NM, van 't Wout JW, Blom JW, Spelt IC, Leyten EM, Koster T, Ablij HC, van der Beek MT, Knol MJ, van Dissel JT. Treatment duration of febrile urinary tract infection: a pragmatic randomized, double-blind, placebo-controlled non-inferiority trial in men and women. BMC Med. 2017 Apr 3;15(1):70. doi: 10.1186/s12916-017-0835-3.

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: December 16, 2008
• First Submitted That Met QC Criteria: December 16, 2008
• First Posted (Estimate): December 17, 2008

Study Record Updates

• Last Update Posted (Estimate): September 16, 2016
• Last Update Submitted That Met QC Criteria: September 15, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Fever; Urinary Tract Infection; Treatment duration; Acute Pyelonephritis; Febrile Urinary Tract Infection Treatment Duration
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Infections; Communicable Diseases; Urinary Tract Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Ciprofloxacin
• Other Study ID Numbers: NL22172.058.08