Reducing Antibiotic Use for Uncomplicated Urinary Tract Infection in General Practice by Treatment With Uva Ursi (UU)- a Comparative Effectiveness Trial (REGATTA)

It is well known that "over-treatment" of straightforward infections should be avoided as far as possible. Evidence-based data on non antibiotic treatment options for common conditions are therefore needed urgently. This randomised-controlled double blind trial examines whether initial herbal treatment with Uva Ursi, and antibiotic treatment only if symptoms persist, reduces antibiotic consumption in uncomplicated urinary tract infections (UTI) without a negative effect on symptom course and rate of recurrent UTIs. In total, 430 patients presenting with typical UTI symptoms will be included by their GPs and receive randomised either herbal treatment with uva ursi (antibiotics only if symptoms persist), or initial antibiotic treatment. Patients record symptom severity and drug intake in a diary and complete a final questionnaire after 28 days.

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infections
• Intervention / Treatment: Drug: Arctuvan; Drug: Placebo to Fosfomycin; Drug: Fosfomycin; Drug: Placebo to Arctuvan

• Study Type: Interventional
• Enrollment (Actual): 398
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Achim, Germany, 28832
    • Hausarztpraxis Dr. Raby
  • Braunschweig, Germany
    • General Practice Aden
  • Braunschweig, Germany
    • General Practice Scheffer
  • Bremen, Germany
    • General Practice Coutelle
  • Bremen, Germany
    • General Practice Schelp
  • Burgwedel, Germany
    • General Practice Dickow
  • Burgwedel, Germany
    • General Practice Kiwit-Putzer
  • Celle, Germany, 29221
    • Praxis Zietz
  • Emmerthal, Germany
    • General Practice Kutzsche
  • Gieboldehausen, Germany, 37434
    • Praxis Dr. Bahr
  • Gillersheim, Germany
    • General Practice Müller
  • Göttingen, Germany
    • General Practice Keske
  • Göttingen, Germany
    • General Practice Koch
  • Göttingen, Germany
    • General Practice Kolb
  • Göttingen, Germany
    • General Practice Lang
  • Göttingen, Germany
    • General Practice Lückerath
  • Göttingen, Germany, 37073
    • Institute of General Medicine, University Medical Center Goettingen
  • Göttingen, Germany, 37083
    • Praxisgemeinschaft Jacob / Kling
  • Hannover, Germany, 30625
    • Institute of General Medicine, MHH Hannover
  • Hannover, Germany
    • General Practice Barth
  • Hannover, Germany, 30161
    • Praxis Dr. Egner
  • Hardegsen, Germany
    • General Practice Löber
  • Heilbad Heiligenstadt, Germany, 37308
    • Gemeinschaftspraxis Dres Schlesier / Eckhardt
  • Heilbad Heiligenstadt, Germany, 37308
    • Gemeinschaftspraxis Hartleb / Stöcking
  • Heilbad Heiligenstadt, Germany, 37308
    • Praxis Dr. Koch
  • Herzberg, Germany, 37412
    • Praxisgemeinschaft Seitz / Eckert
  • Hildesheim, Germany
    • General Practice Wilde
  • Höxter, Germany
    • General Practice Beverungen
  • Höxter, Germany, 37671
    • Praxisgemeinschaft Stoltz / Raddatz
  • Isernhagen, Germany, 30916
    • Gemeinschaftspraxis Kasperczyk / Schindewolf-Lensch
  • Katlenburg-Lindau, Germany
    • General Practice Franz
  • Langenhagen, Germany, 30851
    • Praxis Dr. Ohlendorf
  • Langwedel, Germany
    • General Practice Ertel
  • Lemforde, Germany
    • General Practice Wehrbein
  • Neustadt, Germany
    • General Practice Lindenblatt
  • Nörten-Hardenberg, Germany, 37176
    • Hausarztzentrum Nörten
  • Rehburg-Loccum, Germany
    • General Practice Preiskorn
  • Rosdorf, Germany
    • General Practice Meier-Ahrens
  • Salzgitter, Germany
    • General Practice Woitschek
  • Sattenhausen, Germany
    • General Practice Beulshausen
  • Scheeßel, Germany
    • General Practice Schulte
  • Schwanewede, Germany
    • General Practice Böttcher
  • Springe, Germany
    • General Practice Albrecht
  • Uslar, Germany, 37170
    • General Practice Wolf
  • Verden, Germany
    • General Practice Schmiemann
  • Waake, Germany
    • General Practice Annweiler
  • Wunstorf, Germany
    • General Practice Stegemann

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women (18-75 years) with suspected UTI
• at least two symptoms of UTI (dysuria, urgency of micturition, frequency, lower abdominal pain)
• Written informed consent

Exclusion Criteria:

• signs of complicated UTI (e. g. temperature > 38°C, loin tenderness)
• conditions that may lead to complicated infections (i.e. renal diseases, patients with urinary catheter)
• pregnancy/ breastfeeding
• current self-medication with UU preparations e.g. z.B. Cystinol®, Uvalysat®, Arctuvan®
• antibiotic use in the last 7 days
• previous UTI in the past 2 weeks
• history of pyelonephritis
• contraindications for trial drugs
• serious diseases
• inability to understand trial Information
• current participation in another clinical trial or participation in another clinical trial within the last 4 weeks

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Uva Ursi; placebo to fosfomycin: 3 g granules orally 1x1 (day 0) and Uva Ursi: 105 mg (Arctuvan®) 3x2 tablets orally from day 0 for 5 days	Drug: Arctuvan; application of a herbal drug; Drug: Placebo to Fosfomycin; application of Placebo to Fosfomycin
Active Comparator: fosfomycin; fosfomycin (Monuril®): 3 g granules orally 1x1 (day 0), and placebo to Uva Ursi: 3x2 tablets orally from day 0 for 5 days If the patient returns with persistent/recurrent symptoms, antibiotic therapy according to the sensitivity test.	Drug: Fosfomycin; application of an antibiotic drug; Drug: Placebo to Arctuvan; application of Placebo to Arctuvan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
antibiotic courses	number of antibiotic courses from day 0 to day 28	day 0-28
symptom burden	symptom burden (AUC) from day 0 to day 7	day 0-7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
early relapses	number of early relapses until day 14	day 0-14
recurrent UTI	number of recurrent UTI day 15-28	day 15-28
symptom resolution	number of patients with symptom resolution on day 4/7	day 4 and 7
symptom sum score by patients' questionnaire	mean daily symptom sum scores from day 0 to day 7; Each of the symptoms dysuria, urgency, frequency and lower abdominal pain is scored daily on a five point scale from 0 "none" to 4 "very strong" in a patients' questionnaire.	day 0-7
symptom burden for dysuria	symptom burden (AUC) for dysuria scored daily on a five point scale from 0 "none" to 4 "very strong", from day 0 to day 7	day 0-7
symptom burden positive urine culture	symptom burden (AUC) day 0-7 of patients with positive urine culture	day 0-7
symptom burden negative urine culture	symptom burden (AUC) day 0-7 of patients with negative urine culture	day 0-7
activity impairment by UTI symptoms, measured as AUC	activity impairment by UTI symptoms (days 0-7), measured as AUC. Impairment by each UTI symptom is scored daily on a five point scale from 0 "none" to 4 "very strong".	day 0-7
painkillers	use of painkillers (Defined Daily Dose (DDD) day 0-7)	day 0-7
patients taking painkillers	number of patients taking painkillers	day 28
antibiotic use	antibiotic use (defined daily dose (DDD) day 0-28)	day 0-28
UTI related visits	number of UTI related visits day 0-28	day 0-28
UTI related sick leave	number of days of UTI related sick leave day 0-28	day 0-28
patients with poor outcome: temperature	number of patients with temperature >38°C, day 0-7, according to patients´ statement	day 0-7
patients with poor outcome: worsening symptoms	number of patients with worsening symptoms (impairment in symptom score)	day 28
patients with poor outcome: prolonged symptoms	number of patients with prolonged symptoms (> 7 days), day 0-28. Patients will be followed up until symptom resolution, defined as max. 1 score point on each symptom scale.	day 0-28
pyelonephritis	number of pyelonephritis day 0-28, according to GP´s diagnosis	day 0-28
AE and SAE	number of AE and SAE by system organ class day 0-28	day 0-28
patients with at least 1 AE/ 2 AE	proportion of patients with at least 1 AE/ 2 AE	day 28
symptom burden for urgency	symptom burden (AUC) for urgency scored daily on a five point scale from 0 "none" to 4 "very strong", from day 0 to day 7	day 0-7
symptom burden for frequency	symptom burden (AUC) for frequency scored daily on a five point scale from 0 "none" to 4 "very strong", from day 0 to day 7	day 0-7
symptom burden for lower abdominal pain	symptom burden (AUC) for lower abdominal pain scored daily on a five point scale from 0 "none" to 4 "very strong", from day 0 to day 7	day 0-7

Collaborators and Investigators

• Sponsor: University Medical Center Goettingen
• Investigators: Principal Investigator: Eva Hummers-Pradier, Prof. Dr., University Medical Center Göttingen

Publications and helpful links

General Publications

• Gágyor I, Hummers E, Schmiemann G, Friede T, Pfeiffer S, Afshar K, Bleidorn J. Herbal treatment with uva ursi extract versus fosfomycin in women with uncomplicated urinary tract infection in primary care: a randomized controlled trial. Clin Microbiol Infect. 2021 Oct;27(10):1441-1447. doi: 10.1016/j.cmi.2021.05.032. Epub 2021 Jun 7.
• Afshar K, Fleischmann N, Schmiemann G, Bleidorn J, Hummers-Pradier E, Friede T, Wegscheider K, Moore M, Gagyor I. Reducing antibiotic use for uncomplicated urinary tract infection in general practice by treatment with uva-ursi (REGATTA) - a double-blind, randomized, controlled comparative effectiveness trial. BMC Complement Altern Med. 2018 Jul 3;18(1):203. doi: 10.1186/s12906-018-2266-x.

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2017
• Primary Completion (Actual): May 19, 2019
• Study Completion (Actual): June 20, 2019

Study Registration Dates

• First Submitted: May 10, 2017
• First Submitted That Met QC Criteria: May 10, 2017
• First Posted (Actual): May 12, 2017

Study Record Updates

• Last Update Posted (Actual): November 27, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Uva Ursi; fosfomycin; uncomplicated urinary tract infection of women
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Infections; Communicable Diseases; Urinary Tract Infections; Anti-Infective Agents; Anti-Bacterial Agents; Fosfomycin
• Other Study ID Numbers: 01579

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No