Clinical trial NCT04959331: Clinical Effectiveness and Bacteriological Eradication of 4 Short-course Antibiotics for Uncomplicated UTIs in Women.
Official title: Clinical Effectiveness and Bacteriological Eradication of Three Different Short-course Antibiotic Regimens and Single-dose Fosfomycin for Uncomplicated Lower Urinary Tract Infections in Adult Women.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Urinary Tract Infections
Keywords: Urinary Tract Infections
Women
Patient Outcome Assessment
Bacteriological Eradication
Urinalysis
Anti-Bacterial Agents
Antimicrobial Resistance
Short Course
Primary Health Care
Lead sponsor: Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina
Sponsor class: OTHER
Collaborators: name: Balearic Islands Health Service (Ibsalut)
name: Instituto de Investigación Sanitaria Aragón
name: Gerencia de Atención Primaria, Madrid
First posted: 2021-07-13
Enrollment: 1000
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 3 short-course antibiotic regimens and one-dose of fosfomycin
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Clinical effectiveness.
timeFrame: Day 7.
measure: Bacteriological eradication.
timeFrame: Day 14.
Secondary outcomes:
measure: Duration of symptoms.
timeFrame: From baseline visit to day 7.
measure: Bacteriological eradication.
timeFrame: Day 28.
measure: Relapse rate.
timeFrame: Days 7, 14 and 28.
measure: Reattendance and complication rate.
timeFrame: Days 7, 14 and 28.
measure: Adverse event rate.
timeFrame: Days 7, 14 and 28.
measure: Change in quality of life.
timeFrame: Days 0 and 7.
Other outcomes:
Locations:
city: Calatayud
country: Spain
facility: Calatayud Center
state: Aragón
city: Zaragoza
country: Spain
facility: Las Fuentes Center
state: Aragón
city: Zaragoza
country: Spain
facility: Arrabal Health Center
state: Aragón
city: Zaragoza
country: Spain
facility: Parque Goya Health Center
state: Aragón
city: Calvià
country: Spain
facility: Santa Ponça Health Center
state: Balearic Islands
city: Palma De Mallorca
country: Spain
facility: Emili Darder Center
state: Balearic Islands
city: Palma De Mallorca
country: Spain
facility: Camp Redó Health Center
state: Balearic Islands
city: Palma De Mallorca
country: Spain
facility: Son Pisà Center
state: Balearic Islands
city: Palma De Mallorca
country: Spain
facility: Son Serra-La Vileta Health Center
state: Balearic Islands
city: Santa Maria del Camí
country: Spain
facility: Santa Maria del Camí Center
state: Balearic Islands
city: Banyoles
country: Spain
facility: Banyoles Center
state: Catalonia
city: Corbera De Llobregat
country: Spain
facility: Corbera Center
state: Catalonia
city: Cornellà De Llobregat
country: Spain
facility: La Gavarra Health Center
state: Catalonia
city: El Prat De Llobregat
country: Spain
facility: 17 de Setembre Center
state: Catalonia
city: Esplugues De Llobregat
country: Spain
facility: Can Vidalet Center
state: Catalonia
city: Girona
country: Spain
facility: Santa Clara Center
state: Catalonia
city: Hospitalet de Llobregat
country: Spain
facility: Florida Center
state: Catalonia
city: Hospitalet de Llobregat
country: Spain
facility: Can Serra Center
state: Catalonia
city: Montblanc
country: Spain
facility: Montblanc Center
state: Catalonia
city: Palma De Mallorca
country: Spain
facility: Pere Garau Center
state: Catalonia
city: Sant Boi De Llobregat
country: Spain
facility: Molí Nou Center
state: Catalonia
city: Sant Feliu De Guíxols
country: Spain
facility: Sant Feliu de Guíxols Center
state: Catalonia
city: Sant Just Desvern
country: Spain
facility: Sant Just Desvern Center
state: Catalonia
city: Sant Vicenç Dels Horts
country: Spain
facility: Vila Vella Center
state: Catalonia
city: Tarragona
country: Spain
facility: Jaume I Health Center
state: Catalonia
city: Coslada
country: Spain
facility: El Puerto Center
state: Madrid
city: Coslada
country: Spain
facility: Valleaguado Health Center
state: Madrid
city: San Fernando De Henares
country: Spain
facility: San Fernando Health Center
state: Madrid
city: Villarejo de Salvanés
country: Spain
facility: Villarejo de Salvanés Health Center
state: Madrid
city: Madrid
country: Spain
facility: Los Alpes Health Center
city: Madrid
country: Spain
facility: Aquitania Health Center
city: Madrid
country: Spain
facility: Mar Báltico Center
city: Madrid
country: Spain
facility: Buenos Aires Center
Study officials:
affiliation: Pharmacist
name: Rosa Morros, MD PhD
role: STUDY_CHAIR
References:
citation: Garcia-Sangenis A, Morros R, Aguilar-Sanchez M, Medina-Perucha L, Leiva A, Ripoll J, Martinez-Pecharroman M, Bartolome-Moreno CB, Magallon Botaya R, Marin-Canada J, Molero JM, Moragas A, Troncoso A, Monfa R, Llor C; SCOUT Study Group. Clinical effectiveness and bacteriological eradication of three different Short-COurse antibiotic regimens and single-dose fosfomycin for uncomplicated lower Urinary Tract infections in adult women (SCOUT study): study protocol for a randomised clinical trial. BMJ Open. 2021 Nov 25;11(11):e055898. doi: 10.1136/bmjopen-2021-055898.