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

University Hospitals (UH)

Status and phase

Unknown

Phase 4

Conditions

Urinary Tract Infections

Cystitis

Treatments

Drug: nitrofurantoin

Drug: fosfomycin

Study type

Interventional

Funder types

Other

Identifiers

NCT01966653

13-014

Details and patient eligibility

About

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.

Full 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.

Enrollment

600 estimated patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

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