Clinical Effectiveness and Bacteriological Eradication of 4 Short-course Antibiotics for Uncomplicated UTIs in Women. (SCOUT)

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.

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.

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infections
• Intervention / Treatment: Drug: Fosfomycin Trometamol Salt; Drug: Fosfomycin Trometamol Salt; Drug: Nitrofurantoin; Drug: Pivmecillinam

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.

• Study Type: Interventional
• Enrollment (Actual): 1000
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Aragon
    • Calatayud, Aragon, Spain, 50300
      • Calatayud Center
    • Zaragoza, Aragon, Spain, 50002
      • Las Fuentes Center
    • Zaragoza, Aragon, Spain, 50015
      • Arrabal Health Center
    • Zaragoza, Aragon, Spain, 50018
      • Parque Goya Health Center
  • Balearic Islands
    • Calvià, Balearic Islands, Spain, 07180
      • Santa Ponça Health Center
    • Palma de Mallorca, Balearic Islands, Spain, 07007
      • Emili Darder Center
    • Palma de Mallorca, Balearic Islands, Spain, 07010
      • Camp Redó Health Center
    • Palma de Mallorca, Balearic Islands, Spain, 07011
      • Son Pisà Center
    • Palma de Mallorca, Balearic Islands, Spain, 07013
      • Son Serra-La Vileta Health Center
    • Santa Maria del Camí, Balearic Islands, Spain, 07320
      • Santa Maria del Camí Center
  • Catalonia
    • Banyoles, Catalonia, Spain, 17820
      • Banyoles Center
    • Corbera de Llobregat, Catalonia, Spain, 08757
      • Corbera Center
    • Cornellà de Llobregat, Catalonia, Spain, 08940
      • La Gavarra Health Center
    • Esplugues de Llobregat, Catalonia, Spain, 08950
      • Can Vidalet Center
    • Girona, Catalonia, Spain, 17001
      • Santa Clara Center
    • L'Hospitalet de Llobregat, Catalonia, Spain, 08905
      • Florida Center
    • L'Hospitalet de Llobregat, Catalonia, Spain, 08906
      • Can Serra Center
    • Montblanc, Catalonia, Spain, 43400
      • Montblanc Center
    • Palma de Mallorca, Catalonia, Spain, 07007
      • Pere Garau Center
    • Sant Boi de Llobregat, Catalonia, Spain, 08830
      • Molí Nou Center
    • Sant Feliu de Guíxols, Catalonia, Spain, 17220
      • Sant Feliu de Guíxols Center
    • Sant Just Desvern, Catalonia, Spain, 08960
      • Sant Just Desvern Center
    • Sant Vicenç dels Horts, Catalonia, Spain, 08620
      • Vila Vella Center
    • Tarragona, Catalonia, Spain, 43005
      • Jaume I Health Center
    • el Prat de Llobregat, Catalonia, Spain, 08820
      • 17 de Setembre Center
  • Madrid
    • Coslada, Madrid, Spain, 28821
      • El Puerto Center
    • Coslada, Madrid, Spain, 28823
      • Valleaguado Health Center
    • Madrid, Madrid, Spain, 28022
      • Los Alpes Health Center
    • Madrid, Madrid, Spain, 28032
      • Aquitania Health Center
    • Madrid, Madrid, Spain, 28033
      • Mar Báltico Center
    • Madrid, Madrid, Spain, 28038
      • Buenos Aires Center
    • San Fernando de Henares, Madrid, Spain, 28830
      • San Fernando Health Center
    • Villarejo de Salvanés, Madrid, Spain, 28590
      • Villarejo de Salvanés Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Short-course fosfomycin; 3 g of fosfomycin once daily for two days (sachets)	Drug: Fosfomycin Trometamol Salt; Fosfomycin 3 g 2 sachets, taken orally, once daily for two days; Other Names: Monurol; Drug: Fosfomycin Trometamol Salt; Fosfomycin 3 g one sachet, taken orally, for one day; Other Names: Monurol
Active Comparator: Short-course nitrofurantoin; Five-day nitrofurantoin 100 mg t.i.d. (pills)	Drug: Nitrofurantoin; Nitrofurantoin 50 mg pills, taken orally, two pills/8 hours, for five days; Other Names: Furantoin
Active Comparator: Short-course pivmecillinam; Three-day pivmecillinam 400 mg. t.i.d. (pills)	Drug: Pivmecillinam; Pivmecillinam 400 mg pills. taken orally, one pill/8 hours, for three days; Other Names: Selexid
Active Comparator: Single-dose fosfomycin; Single 3 g dose of fosfomycin (sachet)	Drug: Fosfomycin Trometamol Salt; Fosfomycin 3 g 2 sachets, taken orally, once daily for two days; Other Names: Monurol; Drug: Fosfomycin Trometamol Salt; Fosfomycin 3 g one sachet, taken orally, for one day; Other Names: Monurol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical effectiveness.	Proportion of patients who report being cured, defined as the resolution of the four symptoms, scoring 0 in the symptom diary.	Day 7.
Bacteriological eradication.	Proportion of patients bacteriologically cured, defined as less than 1,000 colony forming units (cfu)/ml.	Day 14.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of symptoms.	Number of days until the last day the patient scores 0 in any of the four symptoms.	From baseline visit to day 7.
Bacteriological eradication.	Proportion of patients bacteriologically cured, defined as less than 1,000 cfu/ml.	Day 28.
Relapse rate.	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.	Days 7, 14 and 28.
Reattendance and complication rate.	Proportion of patients re-attending healthcare services and development of complications within the first 4 weeks (i.e. pyelonephritis, urosepsis).	Days 7, 14 and 28.
Adverse event rate.	Proportion of patients presenting adverse and serious adverse events.	Days 7, 14 and 28.
Change in quality of life.	Change in the quality of life by means of the 5-level EQ-5D version (EQ-5D-5L) validated questionnaire (Spanish version).	Days 0 and 7.

Collaborators and Investigators

• Sponsor: Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina
• Collaborators: Instituto de Investigación Sanitaria Aragón; Gerencia de Atención Primaria, Madrid; Balearic Islands Health Service (Ibsalut)
• Investigators: Study Chair: Rosa Morros, MD PhD, Pharmacist

Publications and helpful links

General Publications

• 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.

Helpful Links

• The protocol of the study will be available on this webpage

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2021
• Primary Completion (Actual): December 14, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: July 5, 2021
• First Submitted That Met QC Criteria: July 12, 2021
• First Posted (Actual): July 13, 2021

Study Record Updates

• Last Update Posted (Estimated): September 8, 2025
• Last Update Submitted That Met QC Criteria: September 1, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Women; Primary Health Care; Patient Outcome Assessment; Urinary Tract Infections; Anti-Bacterial Agents; Short Course; Antimicrobial Resistance; Urinalysis; Bacteriological Eradication
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Infections; Urinary Tract Infections; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amides; Organophosphorus Compounds; Organophosphonates; beta-Lactams; Lactams; Nitro Compounds; Penicillins; Furans; Nitrofurans; Amdinocillin; Fosfomycin; Nitrofurantoin; Amdinocillin Pivoxil
• Other Study ID Numbers: IJG-SCOUT-2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: On request
• IPD Sharing Time Frame: On request after publication.
• IPD Sharing Access Criteria: Principal investigator's email (carles.llor@gmail.com)
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No