Efficacy of CLR Compared to Fosfomycin Trometamol in Acute Lower uUTIs

A Double-blind, Controlled, Parallel-group, Randomized, Multicenter Clinical Trial to Assess the Efficacy and Safety of a Herbal Drug Containing Centaury, Lovage Root and Rosemary Leaf (CLR) in Comparison to Fosfomycin Trometamol for the Treatment of Acute Lower Uncomplicated Urinary Tract Infections (uUTIs) in Women

To demonstrate non-inferiority of a non-antibiotic therapy with CLR versus an antibiotic treatment with fosfomycin trometamol in women suffering from acute lower uUTIs as measured by the proportion of patients who received an additional antibiotic treatment for acute lower uUTIs during the trial.

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infection
• Intervention / Treatment: Drug: Canephron® N; Drug: Fosfomycin trometamol-placebo; Drug: Fosfomycin trometamol; Drug: Canephron® N-placebo

Detailed Description

The trial is designed as a comparison of two different modes of action in order to look for alternatives to antibiotic treatment of uncomplicated UTIs. Treatment with CLR is a nonantibiotic therapy and is compared to an antibiotic treatment. Thus, the trial aim is to reduce antibiotics use and moreover to reduce the pressure of developing bacterial resistance against antibiotics due to widespread use, which is an additional advantage of the CLR therapy.

The trial results are expected to demonstrate that antibiotic prescriptions in women for treatment of lower uUTIs can be reduced by an alternative and safe non-antibiotic treatment.

• Study Type: Interventional
• Enrollment (Actual): 659
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Hessen
    • Giessen, Hessen, Germany, 35392
      • Justus-Liebig-Universität

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Signed informed consent (IC) and data protection declaration
2. Female outpatients aged 18 to 70 years
3. Sum-score of the main uUTI symptoms (dysuria, pollakisuria, and urgency) reported on the Acute Cystitis Symptom Score (ACSS)-"Typical" domain at Visit 1 is ≥6
4. Symptoms of the acute episode of lower uUTI are developed within not more than 6 days prior to Visit 1
5. Leukocyturia at Visit 1, confirmed by positive dipstick
6. Patients willing to refrain from consuming prohibited concomitant medications and products
7. Non-lactating female patients who are surgically sterile (have had a documented sterilization, bilateral oophorectomy at least 3 months before the start of the trial and/or hysterectomy), or postmenopausal (cessation of menses for at least 12 months), or women of childbearing potential with a negative pregnancy test at Visit 1 willing to use highly effective (failure rate less than 1% per year, i.e., Pearl Index <1) contraception methods, e.g., contraceptive patch, oral, injected or implanted hormonal methods of contraception, during the trial including the follow-up period.

Exclusion Criteria:

1. Any signs of complicated urinary tract infections (UTIs), pyelonephritis (i.e., fever T ≥38.0°C [grade 2], flank and/or back pain, chills and shivers), and/or vulvo-vaginitis with vaginal and/or with urethral discharge (without urination) at Visit 1.
2. Any conditions that may lead to complicated infections (i.e., renal diseases, urinary tract abnormalities or past urinary surgery, urine catheterization, uncontrolled diabetes mellitus, spinal cord injury, etc.).
3. Chronic infection of the urinary tract known from medical history.
4. Persisting signs or symptoms of severe, progressive, or uncontrolled systemic disease (i.e., renal, hepatic, biliary, hematological, gastro-intestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease).
5. Uncontrolled hypertension (a diastolic blood pressure >95 mmHg at Visit 1).
6. Known severe cardiac insufficiency, coronary heart disease, valvular heart disease, cardiac arrhythmia, QT interval prolongation or other severe cardiac disease at Visit 1.
7. Any antibiotic therapy within 30 days prior to Visit 1.
8. Other acute infections (except uUTIs) requiring antibiotic treatment at Visit 1.
9. Patients receiving treatment for suspected or confirmed UTI (antibiotic or phytopharmaceutical) within 30 days prior to Visit 1.
10. Patients who took anti-inflammatory drugs (e.g., ibuprofen) or spasmolytics for any reason within 24 hours prior to Visit 1, and/or are not willing to stop the intake of any of the medication not permitted for use during the trial.
11. Known severe impaired renal function (creatinine clearance <20 mL/min).
12. Active peptic ulcers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group Canephron® N; Canephron® N & fosfomycin trometamol-placebo	Drug: Canephron® N; 2 tablets 3 times a day for 7 days; Drug: Fosfomycin trometamol-placebo; 1 sachet of 8 g of granules; one single dose on Day 1
Active Comparator: Group Fosfomycin Trometamol; Canephron® N-placebo & fosfomycin trometamol	Drug: Fosfomycin trometamol; 1 sachet of 8 g of granules; one single dose on Day 1; Drug: Canephron® N-placebo; 2 tablets 3 times a day for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intake of any additional antibiotic medication for acute lower uUTIs between Visit 1 and Visit 4	For patients with consistent or worsening of acute lower uUTI symptoms during the trial the investigator may offer an additional antibiotic therapy at any post-baseline visit. In this case, the patient will be considered a "treatment failure" due to lack of efficacy of the IMP. The alternative antibiotic therapy offered to the patient and the reason for the alternative therapy (i.e., persisting or recurrent symptoms) is to be documented. The primary variable for the assessment of efficacy is the proportion of patients who received additional antibiotic treatment for acute lower uUTI between Visit 1 and Visit 4 (defined as AB-rate).	within 38 days after Visit 1 (=day 1)

Collaborators and Investigators

• Sponsor: Bionorica SE
• Investigators: Principal Investigator: Florian Wagenlehner, Prof., Universitatsklinikum Gießen und Marburg GmbH

Publications and helpful links

General Publications

• Wagenlehner FM, Abramov-Sommariva D, Holler M, Steindl H, Naber KG. Non-Antibiotic Herbal Therapy (BNO 1045) versus Antibiotic Therapy (Fosfomycin Trometamol) for the Treatment of Acute Lower Uncomplicated Urinary Tract Infections in Women: A Double-Blind, Parallel-Group, Randomized, Multicentre, Non-Inferiority Phase III Trial. Urol Int. 2018;101(3):327-336. doi: 10.1159/000493368. Epub 2018 Sep 19.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 29, 2017

Study Registration Dates

• First Submitted: December 11, 2015
• First Submitted That Met QC Criteria: December 21, 2015
• First Posted (Estimate): December 24, 2015

Study Record Updates

• Last Update Posted (Actual): July 28, 2017
• Last Update Submitted That Met QC Criteria: July 26, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Uncomplicated urinary tract infection
• Additional Relevant MeSH Terms: Urologic Diseases; Infections; Urinary Tract Infections; Anti-Infective Agents; Anti-Bacterial Agents; Fosfomycin
• Other Study ID Numbers: CanUTI-7

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