Clinical Effectiveness and Bacteriological Eradication of 4 Short-course Antibiotics for Uncomplicated UTIs in Women.
- Conditions
- Urinary Tract Infections
- Interventions
- Registration Number
- NCT04959331
- Lead Sponsor
- Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina
- Brief Summary
Randomized clinical trial in which women aged 18 or older and with symptoms of uncomplicated lower urinary tract infection and a positive urine dipstick analysis will be randomized to one of the following four groups: 2-day 3 g fosfomycin o.d., 3-day pivmecillinam 400 mg. t.i.d, 5-day nitrofurantoin 100 mg t.i.d. or a single dose of 3 g of fosfomycin. Sample: 1,000 patients. Two co-primary endpoints are considered: clinical effectiveness at day 7 and bacteriological eradication at day 14. Follow-up visits are scheduled at days 7 (phone call), 14 and 28 for assessing evolution. Urine samples will be collected in the three on-site visits and urine cultures performed.
- Detailed Description
Uncomplicated lower urinary tract infections (LUTI) represent a common problem in primary care. Resistance of uropathogens to common antibiotics has significantly increased in the last years. Current local guidelines recommend the use of a single 3 g dose of fosfomycin for these infections, but most general practitioners prefer short-course therapies to single-dose therapy. No study has compared head-to-head short course antimicrobial agents for uncomplicated LUTIs. Therefore, the aim of this randomized clinical trial is to compare three different short-course antibiotic therapies with single-dose fosfomycin for uncomplicated LUTIs in adult women. This will be a pragmatic, multicenter, parallel group, open randomized trial. Women aged 18 or older and with symptoms of uncomplicated LUTI and a positive urine dipstick analysis will be randomized to one of the following four groups: 2-day 3 g fosfomycin o.d., 3-day pivmecillinam 400 mg. t.i.d, 5-day nitrofurantoin 100 mg t.i.d. or a single dose of 3 g of fosfomycin. Sample: 1,000 patients. Two co-primary endpoints are considered: clinical effectiveness, defined as resolution of symptoms, answered by the patients at day 7, and bacteriological eradication (proportion of patients bacteriologically cured) at day 14. Patients will be given a symptom diary for seven days. Follow-up visits are scheduled at days 7 (phone call), 14 and 28 for assessing evolution. Urine samples will be collected in the three on-site visits and urine cultures performed. If positive, antibiograms for the 3 antibiotics studied will be performed.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 1000
Women of 18 years of age or older, with clinical features of uncomplicated community-acquired lower urinary tract infection including:
- At least one of four key symptoms of lower urinary tract infection: dysuria, urgency including nycturia, frequency, and suprapubic tenderness that could be attributed to an uncomplicated lower urinary tract infection, and no alternative explanation (i.e. symptoms suggestive of sexually-transmitted infection or vulvovaginitis), and
- A urine dipstick analysis positive for either nitrites or leukocyte esterase.
- Male sex
- High suspicion of pyelonephritis (i.e. fever ≥ 37.5°C or flank pain/tenderness)
- Any condition that may lead or predispose to complicated urinary infection (i.e. indwelling urinary catheter, pregnancy, immunosuppressive therapy, abnormal urinary tracts, recurrent urinary tract infection, severe neurological disease affecting the bladder)
- Pregnancy or planned pregnancy
- Symptoms consistent with urinary tract infection in the preceding 4 weeks
- Patients taking long-term antibiotic prophylaxis
- Ongoing antibiotic therapy or use of any systemic antibiotic in the previous 7 days
- Symptoms correlating with differential diagnosis (i.e. vaginal discharge or pain)
- Hypersensitivity or allergy to β lactams, nitrofurantoin and/or fosfomycin
- Moderate to severe chronic renal insufficiency
- Pre-existing polyneuropathy
- History of lung or liver reaction or peripheral neuropathy after previous use of nitrofurantoin
- Glucose-6-phosphate dehydrogenase deficiency
- Porphyria or systemic primary carnitine deficiency or of the type organic aciduria (i.e. methylmalonic aciduria and propionicacidaemia)
- Esophageal stricture
- Current intake of allopurinol or probenecid or valproate
- Currently part of another randomized clinical trial
- Previous enrolment in the proposed study
- Patients living in long-term institutions; and/or
- Difficulty in conducting scheduled follow-up visits
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Short-course fosfomycin Fosfomycin Trometamol Salt 3 g of fosfomycin once daily for two days (sachets) Single-dose fosfomycin Fosfomycin Trometamol Salt Single 3 g dose of fosfomycin (sachet) Short-course nitrofurantoin Nitrofurantoin Five-day nitrofurantoin 100 mg t.i.d. (pills) Short-course pivmecillinam Pivmecillinam Three-day pivmecillinam 400 mg. t.i.d. (pills)
- Primary Outcome Measures
Name Time Method Clinical effectiveness. Day 7. Proportion of patients who report being cured, defined as the resolution of the four symptoms, scoring 0 in the symptom diary.
Bacteriological eradication. Day 14. Proportion of patients bacteriologically cured, defined as less than 1,000 colony forming units (cfu)/ml.
- Secondary Outcome Measures
Name Time Method Duration of symptoms. From baseline visit to day 7. Number of days until the last day the patient scores 0 in any of the four symptoms.
Reattendance and complication rate. Days 7, 14 and 28. Proportion of patients re-attending healthcare services and development of complications within the first 4 weeks (i.e. pyelonephritis, urosepsis).
Bacteriological eradication. Day 28. Proportion of patients bacteriologically cured, defined as less than 1,000 cfu/ml.
Adverse event rate. Days 7, 14 and 28. Proportion of patients presenting adverse and serious adverse events.
Relapse rate. Days 7, 14 and 28. Proportion of patients presenting a relapse of symptoms within the first four weeks after inclusion in the study and timing of relapse of symptoms and/or bacteriuria.
Change in quality of life. Days 0 and 7. Change in the quality of life by means of the 5-level EQ-5D version (EQ-5D-5L) validated questionnaire (Spanish version).
Trial Locations
- Locations (33)
Calatayud Center
🇪🇸Calatayud, Aragón, Spain
Parque Goya Health Center
🇪🇸Zaragoza, Aragón, Spain
Montblanc Center
🇪🇸Montblanc, Catalonia, Spain
Pere Garau Center
🇪🇸Palma De Mallorca, Catalonia, Spain
Molí Nou Center
🇪🇸Sant Boi De Llobregat, Catalonia, Spain
Arrabal Health Center
🇪🇸Zaragoza, Aragón, Spain
Santa Ponça Health Center
🇪🇸Calvià, Balearic Islands, Spain
Son Pisà Center
🇪🇸Palma De Mallorca, Balearic Islands, Spain
Son Serra-La Vileta Health Center
🇪🇸Palma De Mallorca, Balearic Islands, Spain
Banyoles Center
🇪🇸Banyoles, Catalonia, Spain
Camp Redó Health Center
🇪🇸Palma De Mallorca, Balearic Islands, Spain
Corbera Center
🇪🇸Corbera De Llobregat, Catalonia, Spain
Can Vidalet Center
🇪🇸Esplugues De Llobregat, Catalonia, Spain
Santa Clara Center
🇪🇸Girona, Catalonia, Spain
Florida Center
🇪🇸Hospitalet de Llobregat, Catalonia, Spain
Can Serra Center
🇪🇸Hospitalet de Llobregat, Catalonia, Spain
Sant Feliu de Guíxols Center
🇪🇸Sant Feliu De Guíxols, Catalonia, Spain
El Puerto Center
🇪🇸Coslada, Madrid, Spain
Valleaguado Health Center
🇪🇸Coslada, Madrid, Spain
San Fernando Health Center
🇪🇸San Fernando De Henares, Madrid, Spain
Los Alpes Health Center
🇪🇸Madrid, Spain
Villarejo de Salvanés Health Center
🇪🇸Villarejo de Salvanés, Madrid, Spain
Aquitania Health Center
🇪🇸Madrid, Spain
Buenos Aires Center
🇪🇸Madrid, Spain
Mar Báltico Center
🇪🇸Madrid, Spain
Las Fuentes Center
🇪🇸Zaragoza, Aragón, Spain
Emili Darder Center
🇪🇸Palma De Mallorca, Balearic Islands, Spain
Santa Maria del Camí Center
🇪🇸Santa Maria del Camí, Balearic Islands, Spain
La Gavarra Health Center
🇪🇸Cornellà De Llobregat, Catalonia, Spain
17 de Setembre Center
🇪🇸El Prat De Llobregat, Catalonia, Spain
Vila Vella Center
🇪🇸Sant Vicenç Dels Horts, Catalonia, Spain
Sant Just Desvern Center
🇪🇸Sant Just Desvern, Catalonia, Spain
Jaume I Health Center
🇪🇸Tarragona, Catalonia, Spain