Study Comparing Nitrofurantoin to Fosfomycin for Acute Urinary Tract Infection in Women (AIDA-WP2)

May 1, 2017 updated by: Stephen Harbarth, University Hospital, Geneva

Randomised Clinical Trial Comparing Fosfomycin vs. Nitrofurantoin for Treatment of Uncomplicated Lower Urinary Tract Infection in Female Adults at Increased Risk of Antibiotic-resistant Bacterial Infection

Developed before the establishment of a structured process for drug assessment, nitrofurantoin is now being prescribed frequently given the rise in multi-resistant gram-negative pathogens. Doubts remain regarding fosfomycin's long-term clinical effectiveness. A randomized, controlled trial is needed to explore the clinical effectiveness and better define the side effect profiles of both nitrofurantoin and fosfomycin. This multi-center open trial will randomize 600 non-pregnant women at three international sites (200 each in Poland, Switzerland, and Israel) at increased risk for carriage of resistant uropathogens and with suspicion of uncomplicated lower urinary tract infection to receive either oral nitrofurantoin 100 mg three times daily for 5 days or a single 3g dose of oral fosfomycin. Patients will be followed for clinical and bacteriologic response at days 14 and 28 post therapy completion. The study hypothesis holds that nitrofurantoin will be superior to fosfomycin in clinical efficacy at final follow-up.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Developed before the establishment of a structured process for drug assessment, nitrofurantoin is now being prescribed frequently given the rise in multi-resistant gram-negative pathogens. Doubts remain regarding fosfomycin's long-term clinical effectiveness. A randomized, controlled trial is needed to explore the clinical effectiveness and better define the side effect profiles of both nitrofurantoin and fosfomycin. From autumn 2013 through summer 2016, this multi-center open trial will randomize 600 non-pregnant women at three international sites (200 each in Poland, Switzerland, and Israel) at increased risk for carriage of resistant uropathogens and with suspicion of uncomplicated lower urinary tract infection to receive either oral nitrofurantoin 100 mg three times daily for 5 days or a single 3g dose of oral fosfomycin. Patients will be followed for clinical and bacteriologic response at days 14 and 28 post therapy completion. The study hypothesis holds that nitrofurantoin will be superior to fosfomycin in clinical efficacy at final follow-up.

Study Type

Interventional

Enrollment (Anticipated)

600

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Tel Aviv, Israel
        • Tel Aviv University
  • Poland
      • Lodz, Poland
        • Lodz University Hospital
  • Switzerland
      • Geneva, Switzerland, 1201
        • University Hospitals of Geneva

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Female gender
  • Age ≥ 18 years
  • Written informed consent
  • At least one of four key UTI symptoms that could be attributed to an uncomplicated UTI, and no alternative explanation (i.e. symptoms suggestive of STI or vulvo-vaginitis):
  • Dysuria
  • Urgency (including nocturia)
  • Frequency
  • Suprapubic tenderness
  • Urine dipstick test positive for either nitrites or leukocyte esterase
  • Patient is at increased risk for resistant pathogens, e.g., FQ-resistant or ESBL-producing Enterobacteriacae

Exclusion Criteria:

  • Male sex
  • Pregnancy or planned pregnancy
  • Known carriage of nitrofurantoin- or fosfomycin-resistant uropathogens(s)
  • Concomitant antimicrobial therapy
  • Use of any antibiotics in the past 7 days
  • Known or suspected hypersensitivity or allergy to fosfomycin or nitrofurantoin
  • History of lung or liver reaction or peripheral neuropathy after use of nitrofurantoin or other nitrofurans in the past
  • Pre-existing polyneuropathy
  • G6PD deficiency
  • Symptoms consistent with UTI in the preceding 4 weeks
  • Active upper UTI (e.g. pyelonephritis, urosepsis: fever > 38.0, flank pain, chills)
  • Symptoms/signs suggestive of vaginitis or sexually transmitted infection
  • Indwelling catheter, nephrostomy, ureter stent or other foreign material
  • Otherwise complicated UTI:
  • A history of anatomical or functional abnormalities of the urogenital tract:
  • Congenital abnormalities
  • Polycystic kidney disease
  • Obstruction or stricture of renal pelvis, ureter or urethra
  • Kidney stones
  • Cystocele
  • Cystic diverticulae
  • Change of anatomical proportions (e.g. after ureter implantation)
  • Chronic vesico-urethral reflux
  • Neurogenic bladder
  • Severe chronic renal (creatinine clearance < 30 ml/min) or hepatic dysfunction
  • Porphyria
  • Immunosuppression:
  • Untreated infection with the human immunodeficiency virus (HIV)
  • Use of high-dose systemic corticosteroids or other immunosuppressive medication
  • Chemotherapy
  • Treatment with radiation
  • Critical illness requiring intensive care
  • Planned surgery within the next 6 weeks
  • Inability to take oral drugs
  • Participation in another prospective clinical trial
  • Previous enrolment in the proposed study
  • Inability to understand or to follow the study protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: nitrofurantoin
Nitrofurantoin will be given orally at a dose of 100 mg three times daily for 5 days.
Drug: nitrofurantoin
nitrofurantoin 100 mg po tid for 5 days
Other Names:
  • Macrodantin
  • Furadantine
Active Comparator: fosfomycin
A single 3g dose of oral fosfomycin will be given.
Drug: fosfomycin
fosfomycin 3g po single dose
Other Names:
  • Monuril

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with clinical cure, clinical failure, or indeterminate clinical response (see description below)
Time Frame: at 28 days post therapy completion
Clinical response is defined as either (1) clinical cure, which in turn is defined as complete resolution of symptoms with no recurrence of symptoms or signs of urinary tract infection; (2) clinical failure, defined as the need for additional, or change in, antibiotic treatment due to a urinary tract infection, OR discontinuation due to lack of efficacy; or (3) indeterminate response, defined as either persistence of symptoms without objective evidence of infection (absence of bacteriuria or pyuria) OR any extenuating circumstances precluding a classification or clinical cure/failure.
at 28 days post therapy completion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with bacteriologic cure and with bacteriologic recurrence
Time Frame: at 28 days post therapy completion
Bacteriologic response is defined as either (1) bacteriologic cure, that is, eradication of the infecting strain with no recurrence of bacteriuria (<10x3 cfu/mL) during follow-up; or (2) bacteriologic recurrence, defined as bacteriuria >10x3 cfu/mL. However, bacteriologic recurrence without urinary tract symptoms will be designated asymptomatic bacteriuria and left untreated.
at 28 days post therapy completion

Other Outcome Measures

Outcome Measure
Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: within 28 days post therapy completion
within 28 days post therapy completion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Geneva

Collaborators

European Commission

Investigators

  • Principal Investigator: Stephan Harbarth, MD, MS, University of Genova

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2013

Primary Completion (Anticipated)

May 1, 2017

Study Completion (Anticipated)

August 1, 2017

Study Registration Dates

First Submitted

October 10, 2013

First Submitted That Met QC Criteria

October 16, 2013

First Posted (Estimate)

October 21, 2013

Study Record Updates

Last Update Posted (Actual)

May 2, 2017

Last Update Submitted That Met QC Criteria

May 1, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13-014

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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