Study Comparing Nitrofurantoin to Fosfomycin for Acute Urinary Tract Infection in Women

NCT01966653 | Unknown Phase 4 DMC

• 1 other identifier: 13-014
• Study Type: interventional
• Target: 600
• Locations: 3 countries
• Sites: 3

Brief Summary

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.

Conditions

Urinary Tract Infections; Cystitis

Keywords

nitrofurantoin; fosfomycin; urinary tract infection; clinical efficacy; bacteriologic response

Outcome Measures

Primary Outcomes (1)

• Number of participants with clinical cure, clinical failure, or indeterminate clinical response (see description below)

  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 Outcomes (1)

• Number of participants with bacteriologic cure and with bacteriologic recurrence

  at 28 days post therapy completion

Other Outcomes (1)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  within 28 days post therapy completion

Study Arms (2)

nitrofurantoin

ACTIVE COMPARATOR

Nitrofurantoin will be given orally at a dose of 100 mg three times daily for 5 days.

Drug: nitrofurantoin

fosfomycin

ACTIVE COMPARATOR

A single 3g dose of oral fosfomycin will be given.

Drug: fosfomycin

Interventions

nitrofurantoin DRUG

nitrofurantoin 100 mg po tid for 5 days

Also known as: Macrodantin, Furadantine

nitrofurantoin

fosfomycin DRUG

fosfomycin 3g po single dose

Also known as: Monuril

fosfomycin

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• University Hospital, Geneva: lead
• European Commission: collaborator

Study Sites (3)

Tel Aviv University

Tel Aviv, Israel

Location

Lodz University Hospital

Lodz, Poland

Location

University Hospitals of Geneva

Geneva, 1201, Switzerland

Location

Related Publications (1)

• Huttner A, Kowalczyk A, Turjeman A, Babich T, Brossier C, Eliakim-Raz N, Kosiek K, Martinez de Tejada B, Roux X, Shiber S, Theuretzbacher U, von Dach E, Yahav D, Leibovici L, Godycki-Cwirko M, Mouton JW, Harbarth S. Effect of 5-Day Nitrofurantoin vs Single-Dose Fosfomycin on Clinical Resolution of Uncomplicated Lower Urinary Tract Infection in Women: A Randomized Clinical Trial. JAMA. 2018 May 1;319(17):1781-1789. doi: 10.1001/jama.2018.3627.

  PMID: 29710295 DERIVED

Related Links

• Related info.

MeSH Terms

Conditions

Urinary Tract Infections; Cystitis

Interventions

Nitrofurantoin; Fosfomycin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitrofurans; Nitro Compounds; Organic Chemicals; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Organophosphonates; Organophosphorus Compounds

Study Officials

• Stephan Harbarth, MD, MS

  University of Geneva

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 10, 2013
• First Posted: October 21, 2013
• Study Start: October 1, 2013
• Primary Completion: May 1, 2017
• Study Completion: August 1, 2017
• Last Updated: May 2, 2017

Record last verified: 2017-05

Locations

IL (1); PL (1); CH (1)