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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University Hospital, Geneva
Sponsor:
Collaborator:
European Commission
Information provided by (Responsible Party):
Stephen Harbarth, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01966653
First received: October 10, 2013
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Urinary Tract Infections
Cystitis
Drug: nitrofurantoin
Drug: fosfomycin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Number of participants with clinical cure, clinical failure, or indeterminate clinical response (see description below) [ Time Frame: at 28 days post therapy completion ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of participants with bacteriologic cure and with bacteriologic recurrence [ Time Frame: at 28 days post therapy completion ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: within 28 days post therapy completion ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 600
Study Start Date: October 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Monuril

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01966653

Contacts
Contact: Stephan Harbarth, MD, MS 41-22-372-3357 stephan.harbarth@hcuge.ch
Contact: Angela Huttner, MD 41-22-557-3396 angela.huttner@hcuge.ch

Locations
Israel
Tel Aviv University Recruiting
Tel Aviv, Israel
Contact: Leonard Leibovici, MD       leibovic@post.tau.ac.il   
Principal Investigator: Leonard Leibovici, MD         
Poland
Lodz University Hospital Recruiting
Lodz, Poland
Contact: Maciek Godycki-Cwirko       maciekgc@uni.lodz.pl   
Principal Investigator: Maciek Godycki-Cwirko, MD         
Switzerland
University Hospitals of Geneva Recruiting
Geneva, Switzerland, 1201
Contact: Stephan Harbarth, MD, MS       stephan.harbarth@hcuge.ch   
Contact: Angela Huttner, MD       angela.huttner@hcuge.ch   
Principal Investigator: Stephan Harbarth, MD, MS         
Sub-Investigator: Angela Huttner, MD         
Sponsors and Collaborators
University Hospital, Geneva
European Commission
Investigators
Principal Investigator: Stephan Harbarth, MD, MS University of Geneva
  More Information

Additional Information:
No publications provided

Responsible Party: Stephen Harbarth, Professor Stephan Harbarth, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT01966653     History of Changes
Other Study ID Numbers: 13-014
Study First Received: October 10, 2013
Last Updated: August 4, 2014
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Geneva:
nitrofurantoin
fosfomycin
urinary tract infection
clinical efficacy
bacteriologic response

Additional relevant MeSH terms:
Urinary Tract Infections
Infection
Communicable Diseases
Urologic Diseases
Fosfomycin
Nitrofurantoin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents, Urinary
Renal Agents

ClinicalTrials.gov processed this record on October 19, 2014