Cystitis, Urinary Tract Infections
Conditions
Keywords
nitrofurantoin, fosfomycin, urinary tract infection, clinical efficacy, bacteriologic response
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.
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.
Interventions
DRUGnitrofurantoin
nitrofurantoin 100 mg po tid for 5 days
DRUGfosfomycin
fosfomycin 3g po single dose
Sponsors
European Commission
University Hospital, Geneva
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with clinical cure, clinical failure, or indeterminate clinical response (see description below) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with bacteriologic cure and with bacteriologic recurrence | 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. |
Other
| Measure | Time frame |
|---|---|
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | within 28 days post therapy completion |
Countries
Israel, Poland, Switzerland
Outcome results
None listed