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

Sponsor

Jordi Gol i Gurina Foundation (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04959331

Collaborator

Balearic Islands Health Service (Ibsalut) (Other), Instituto de Investigación Sanitaria Aragón (Other), Gerencia de Atención Primaria, Madrid (Other)

1,000

Enrollment

Locations

Arms

18.9

Anticipated Duration (Months)

76.9

Patients Per Site

4.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Urinary Tract Infections	Drug: Fosfomycin Trometamol Salt Drug: Nitrofurantoin Drug: Pivmecillinam Drug: Fosfomycin Trometamol Salt	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

1000 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

3 short-course antibiotic regimens and one-dose of fosfomycin3 short-course antibiotic regimens and one-dose of fosfomycin

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Anticipated Study Start Date :

Nov 2, 2021

Anticipated Primary Completion Date :

May 15, 2023

Anticipated Study Completion Date :

May 30, 2023

Arms and Interventions

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
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 one sachet, taken orally, for one day Other Names: Monurol

Outcome Measures

Primary Outcome Measures

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 cfu/ml.

Secondary Outcome Measures

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.
Bacteriological eradication. [Day 28.]
Proportion of patients bacteriologically cured, defined as less than 1,000 cfu/ml.
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.
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).
Adverse event rate. [Days 7, 14 and 28.]
Proportion of patients presenting adverse and serious adverse events.
Change in quality of life. [Days 0 and 7.]
Change in the quality of life by means of the EQ-5D-5L validated questionnaire (Spanish version).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arrabal Health Center	Zaragoza	Aragón	Spain	50015
2	Parque Goya Health Center	Zaragoza	Aragón	Spain	50018
3	Santa Ponça Health Center	Calvià	Balearic Islands	Spain	07180
4	Escola Graduada Health Center	Palma De Mallorca	Balearic Islands	Spain	07002
5	Camp Redó Health Center	Palma De Mallorca	Balearic Islands	Spain	07010
6	Son Serra-La Vileta Health Center	Palma De Mallorca	Balearic Islands	Spain	07013
7	La Gavarra Health Center	Cornellà De Llobregat	Catalonia	Spain
8	Jaume I Health Center	Tarragona	Catalonia	Spain	43005
9	Valleaguado Health Center	Coslada	Madrid	Spain	28823
10	San Fernando Health Center	San Fernando De Henares	Madrid	Spain	28830
11	Villarejo de Salvanés Health Center	Villarejo de Salvanés	Madrid	Spain	28590
12	Los Alpes Health Center	Madrid		Spain	28022
13	Aquitania Health Center	Madrid		Spain	28032