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

Urinary Tract Infections Clinical Trial

— SCOUT  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04959331
• Other study ID #: IJG-SCOUT-2021
• Status: Recruiting
• Phase: Phase 4
• Start date: November 2, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: December 2023
• Source: Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina
• Contact: Ana Garcia-Sangenís, MD
• Phone: 0034638687717
• Email: agarcia[@]idiapjgol.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 31, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 ß 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

Related Conditions & MeSH terms

• Infections
• Urinary Tract Infections

Intervention

Drug:
• Fosfomycin Trometamol Salt
Fosfomycin 3 g 2 sachets, taken orally, once daily for two days
• Nitrofurantoin
Nitrofurantoin 50 mg pills, taken orally, two pills/8 hours, for five days
• Pivmecillinam
Pivmecillinam 400 mg pills. taken orally, one pill/8 hours, for three days
• Fosfomycin Trometamol Salt
Fosfomycin 3 g one sachet, taken orally, for one day

Locations

Country	Name	City	State
Spain	Banyoles Center	Banyoles	Catalonia
Spain	Calatayud Center	Calatayud	Aragón
Spain	Santa Ponça Health Center	Calvià	Balearic Islands
Spain	Corbera Center	Corbera De Llobregat	Catalonia
Spain	La Gavarra Health Center	Cornellà De Llobregat	Catalonia
Spain	El Puerto Center	Coslada	Madrid
Spain	Valleaguado Health Center	Coslada	Madrid
Spain	17 de Setembre Center	El Prat De Llobregat	Catalonia
Spain	Can Vidalet Center	Esplugues De Llobregat	Catalonia
Spain	Santa Clara Center	Girona	Catalonia
Spain	Can Serra Center	Hospitalet de Llobregat	Catalonia
Spain	Florida Center	Hospitalet de Llobregat	Catalonia
Spain	Aquitania Health Center	Madrid
Spain	Buenos Aires Center	Madrid
Spain	Los Alpes Health Center	Madrid
Spain	Mar Báltico Center	Madrid
Spain	Montblanc Center	Montblanc	Catalonia
Spain	Camp Redó Health Center	Palma De Mallorca	Balearic Islands
Spain	Emili Darder Center	Palma De Mallorca	Balearic Islands
Spain	Pere Garau Center	Palma De Mallorca	Catalonia
Spain	Son Pisà Center	Palma De Mallorca	Balearic Islands
Spain	Son Serra-La Vileta Health Center	Palma De Mallorca	Balearic Islands
Spain	San Fernando Health Center	San Fernando De Henares	Madrid
Spain	Molí Nou Center	Sant Boi De Llobregat	Catalonia
Spain	Sant Feliu de Guíxols Center	Sant Feliu De Guíxols	Catalonia
Spain	Sant Just Desvern Center	Sant Just Desvern	Catalonia
Spain	Vila Vella Center	Sant Vicenç Dels Horts	Catalonia
Spain	Santa Maria del Camí Center	Santa Maria del Camí	Balearic Islands
Spain	Jaume I Health Center	Tarragona	Catalonia
Spain	Villarejo de Salvanés Health Center	Villarejo de Salvanés	Madrid
Spain	Arrabal Health Center	Zaragoza	Aragón
Spain	Las Fuentes Center	Zaragoza	Aragón
Spain	Parque Goya Health Center	Zaragoza	Aragón

Sponsors (4)

Lead Sponsor	Collaborator
Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina	Balearic Islands Health Service (Ibsalut), Gerencia de Atención Primaria, Madrid, Instituto de Investigación Sanitaria Aragón

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	Bacteriological eradication.	Proportion of patients bacteriologically cured, defined as less than 1,000 colony forming units (cfu)/ml.	Day 14.
Secondary	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.
Secondary	Bacteriological eradication.	Proportion of patients bacteriologically cured, defined as less than 1,000 cfu/ml.	Day 28.
Secondary	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.
Secondary	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.
Secondary	Adverse event rate.	Proportion of patients presenting adverse and serious adverse events.	Days 7, 14 and 28.
Secondary	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.

External Links

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