Clinical Studies

Clinical Studies

We take a UNIQUE approach to UTI prevention.

URIEXO®…SHIELDS your patients from recurring UTIs.

New non-prescription URIEXO® is a clinically proven non-antibiotic option to UTI prevention.  Only URIEXO® has two clinically proven active ingredients against E. Coli that act as a competitive inhibitor by binding the bacteria at two separate sites of the bacterial surface.  This means that URIEXO® attracts and binds with E. Coli so that the bacteria can be occupied and safely rinsed, preventing it from binding with your urinary tract instead.

D-MANNOSE: First Shield against Recurrent UTIs

  • D-Mannose is a naturally occurring sugar similar in structure to but metabolized differently from glucose so that it does not negatively impact glycemic (blood sugar) control.
  • Binds to Type I Fimbriae (Short Pili) bacteria anchoring sites.
    • Type I fimbriae are proteins on the surface of bacteria that play a pivotal role in bacterial adhesion and the most common virulence factor of UroPathogenic Escherichia coli (UPEC) Infections. 1
    • Type I fimbriae are major facilitators of UPEC entry into Host cells, and prevalent adhesins expressed by most of the pathogenic strains.2
    • Bacteria expressing Type I pili are most frequently associated with infections in the lower urinary tract and bladder causing cystitis. 2,3
  • Clinically proven effective dose for prevention of UTIs (24 hour protection) : 2000 mg/day.

Sources:
1: Rosana Ribic, Acta Pharma. 68 (2018) 1-18 https://dpo.org/10.2478/acph-2018-004
2: Joaquim Ruiz, Difference in Virulence Factors among Clinical Isolates of Excherichia coli Causing Cystitis and Pyelonephritis in Women and Prostatitis in Men, Journal Of Clincial Microbiology, Dec. 2002, p. 4445-4449
3: Magnus Anderson et al, The Biomechanical Properties of E. coli Pili for Urinary Tract Attachment Reflect the Host Environment, Biophysical Journal Volume 93, November 2007, 3008-3014

D-MANNOSE AND UTIs: Human Trial #1

D-Mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial

Bojana Kranjceec, Dino Papes, Silvio Altarac

World J. Urol. (2014) 32:79–84, DOI 10.1007/s00345-013-1091-6

Objective: To test whether D-Mannose powder is effective for recurrent urinary tract infection (UTI) prevention.

Materials and methods: After initial antibiotic treatment of acute cystitis, 308 women with history of recurrent UTIs and no other significant co-morbidity were randomly allocated to three groups. The first group (n = 103) received prophylaxis with 2 g of D-Mannose powder in 200 ml of water daily for 6 months, the second (n = 103) received 50 mg Nitrofurantoin daily, and the third (n = 102) did not receive prophylaxis.

Summary: In short, 2-grams of D-Mannose powder significantly reduced the risk of contracting a recurrent UTI. In addition, D-Mannose performed as well as antibiotics, but without the long-term risks of antibiotic resistance, and with a significantly lower risk of short-term side effects (RR 0.276, P < 0.0001).

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D-Mannose performed as well as antibiotics in reducing recurrent urinary tract infections (15% incidence vs. 20% incidence), but with significantly lower risk of side effects.

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Patient compliance (assessed by recording the intake of prophylaxis on a self-report sheet) was very high and there was no difference between patients taking nitrofurantoin or D-Mannose.

D-MANNOSE AND UTIs: Human Trial #2

Oral D-Mannose in recurrent urinary tract infections in women: a pilot study

D. Porru, A. Parmigiani, C. Tinelli, D. Barletta, D. Choussos, C. Di Franco, V. Bobbi, S. Bassi, O. Miller, B. Gardella, R.E. Nappi, A. Spinillo and B. Rovereto

Journal of Clinical Urology, 2014, Vol. 7(3) 208–213

Objective: Evaluate the efficacy of D-Mannose in the treatment and prophylaxis of recurrent UTIs.

Materials and Methods: In this randomized cross-over trial, female patients were eligible for the study if they had an acute symptomatic UTI and three or more recurrent UTIs during the preceding 12 months. Suitable patients were randomly assigned to antibiotic treatment with trimethoprim/sulfamethoxazole (2 times a day for 5 days, followed by a single dose at bedtime for 1 week each month for 23 weeks) or to a regimen of oral 3g D-Mannose/day (1 g 3 times a day, every 8 hours for 2 weeks), and subsequently 2g D-Mannose/day (1 g twice a day for 22 weeks). Each participant switched groups 24 weeks into the study, so they experienced both types of treatment. The primary endpoint was evaluation of the elapsed time to recurrence; secondary endpoints were evaluation of bladder pain (VASp) and urinary urgency (VASu).

Summary: Mean VAS pain, VAS urgency score, and average numbers of 24-hour voidings decreased significantly. D-Mannose appeared to be a safe and effective treatment for recurrent UTIs in adult women. A significant difference was observed in the proportion of women remaining infection free versus antibiotic treatment. The average results were 52.7 days with the antibiotic treatment, and 200 days with the D-Mannose treatment (p < 0.0001).

A significant difference was observed in the proportion of women remaining infection free versus antibiotic treatment… average results were 52.7 days with the antibiotic treatment, and 200 days with the D-Mmannose treatment (p < 0.0001).

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Mean VAS pain, VAS urgency score, and average numbers of 24-hour voidings decreased significantly. D-Mannose appeared to be a safe and effective treatment for recurrent UTIs in adult women (p < 0.001).

D-MANNOSE AND UTIs: Human Trial #3

D-Mannose: a promising support for acute urinary tract infections in women. A pilot study

L. DOMENICI, M. MONTI, C. BRACCHI, M. GIORGINI, V. COLAGIOVANNI, L. MUZII, P. BENEDETTI PANICI

European Review for Medical and Pharmacological Sciences, 2016; 20: 2920-2925

Objective: Determine whether D-Mannose alone is effective in treating acute urinary tract infections in women and its possible utility in the management of recurrences.

Materials and Methods:  Patients were administered 3 grams of D-Mannose/day (1.5-grams of D-Mannose along with sodium bicarbonate, sorbitol and silicon dioxide 2 times a day for 3 days) and then 1.5 grams of D-Mannose/day (1 time a day for 10 days) , and then randomized into two groups.  After the treatment, one group received D-Mannose treatments (1.5 grams of D-Mannose/day) 1 week per month, every other month. The other group remained untreated. Changes in patients’ symptoms, therapeutic effects, and changes in quality of life (QoL) were evaluated clinically with a validated questionnaire (UTISA).

Summary: Mean UTISA scores recorded after completing the treatment demonstrated a significant improvement for the majority of symptoms when compared to baseline (p <0.05).  D-Mannose had a significant positive effect on UTIs’ resolution and QoL improvement.  As a prophylactic agent administered for 6 months, overall rate of UTI recurrence was 4.5% in the group treated with D-Mannose and 33.3% in the other group.  The median time to recurrent cystitis symptom onset was 43 days and 28 days for D-Mannose vs. control, respectively.

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As a prophylactic agent administered for 6 months, overall rate of UTI recurrence was 4.5% in the group treated with D-mannose and 33.3% in the other group.

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As a prophylactic agent administered for 6 months median time to recurrent cystitis symptom onset was 43 days and 28 days for D-mannose vs. control, respectively.

Proanthocyanidins (PAC) 36mg: Second Shield against Recurrent UTIs

  •  PACs bind to receptors on the bacteria to reduce possibility of adhering to the bladder or urinary tract, allowing for natural flushing of the bacteria during urination
  • Binds to P Pili (Long Pili) bacteria anchoring sites.
    • P Pili (long Pili) are also proteins on the surface of bacteria and are the second common virulence factor of UroPathogenic Escherichia coli (UPEC)1
    • Bacteria expressing P pili are most frequently associated with infections in the upper urinary tract and kidney region causing pyelonephritis (infection of the kidneys) 3
  • Clinically proven effective dose for prevention of UTIs (24 hour protection) : 36mg PACs

Sources:
1: Rosana Ribic, Acta Pharma. 68 (2018) 1-18 https://dpo.org/10.2478/acph-2018-004
2: Joaquim Ruiz, Difference in Virulence Factors among Clinical Isolates of Excherichia coli Causing Cystitis and Pyelonephritis in Women and Prostatitis in Men, Journal Of Clincial Microbiology, Dec. 2002, p. 4445-4449.
3: Magnus Anderson et al, The Biomechanical Properties of E. coli Pili for Urinary Tract Attachment Reflect the Host Environment, Biophysical Journal Volume 93, November 2007, 3008-3014.

PACs and UTIs: Human Trial #1

Cranberry juice capsules and urinary tract infection post-surgery: Results of a randomized trial

Betsy Foxman, Ph.D., Ms. Anna E.W. Cronenwett, B.A., Cathie Spino, ScD, Mitchell B. Berger, M.D., Ph.D, and Daniel M. Morgan, M.D

Am J Obstet Gynecol. 2015 August; 213(2): 194.e1–194.e8. doi:10.1016/j.ajog.2015.04.003.

Objective: The study is the first randomized, double-blind, placebo-controlled trial of the therapeutic efficacy of cranberry juice capsules in preventing UTIs post-surgery among women undergoing elective gynecological surgery where a catheter is placed.

Materials and Methods:  Eligible participants were undergoing elective gynecologic surgery that did not involve a fistula repair or vaginal mesh removal.  160 patients were randomized and received two capsules containing 36 mg Proanthocyanidins (PACs) twice a day, for 6 weeks after surgery, or matching placebo. The primary endpoint was the proportion of participants who experienced clinically-diagnosed and treated UTIs with or without positive urine culture.

Summary: The occurrence of UTIs was significantly lower in the 36 mg Proanthocyanidins (PACs)  treatment group compared to the placebo group (15/80 (19%) versus 30/80 (38%); OR=0.38; 95% CI: 0.19, 0.79; p=0.008). There were no treatment differences in the incidence of adverse events; including gastrointestinal upset (56% vs. 61% for cranberry vs. placebo).

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Among women undergoing elective benign gynecological surgery involving urinary catheterization, use of 36 mg Proanthocyanidins (PACs) tablets during the postoperative period reduced the rate of UTIs by half.

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The median time to UTIs was significantly longer among those in the 36 mg Proanthocyanidins (PACs) group than the placebo group (18 days versus 8.5 days, Figure 2, log rank test p=0.0005).

Time to urinary tract infection by treatment group Kaplan-Meier estimates and 95% Hall-Wellner confidence bands are provided by treatment group. The number at risk for UTIs is shown on the horizontal axis.

PACs and UTIs: Human Trial #2

Dosage effect on uropathogenic Escherichia coli anti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double blind study

Amy B Howell, Henry Botto, Christophe Combescure, Anne-Béatrice Blanc-Potard, Lluis Gausa, Tetsuro Matsumoto, Peter Tenke, Albert Sotto and Jean-Philippe Lavigne

BMC Infectious Diseases 2010, 10:94

Objective:  Investigate the persistence in urine samples over a broader time period, to determine the most effective dose per day of Proanthocyanidins (PAC) to inhibit P-fimbriated E. coli adhesion to uroepithelial cells.

Materials and Methods:  Two separate bioassays (a mannose-resistant hemagglutination assay and an original new human T24 epithelial cell-line assay) have assessed the ex-vivo urinary bacterial anti-adhesion activity on urine samples collected from 32 volunteers in a randomized, double-blind versus placebo study. An in vivo Caenorhabditis elegans model was used to evaluate the influence of cranberry regimen on the virulence of E. coli strain.

Summary:  It was found that 36 mg of PACs (proanthocyanidins Type A) a day is necessary to inhibit bacterial adhesion to the epithelial cell lining of the urinary tract and is efficacious for UTI prevention. Likewise, 36 mg of PACs demonstrated anti-adhesion activity between hours 1 to 6, with peak onset at 6 hours (evident by low anti-adhesion scores following urine sample analysis of both doses).  It was found that 72 mg of PACs (double-dose) may be taken for 2 days for maximum efficacy in protection against bacterial adhesion. This effect may offer nyctohemeral protection (AM/PM). Anti-adhesion benefits remained significant at 24 hours.

PACs and UTIs: Human Trial #3

Does cranberry have a role in catheter-associated urinary tract infections?

Dominique Thomas, BS; Matthew Rutman, MD; Kimberly Cooper, MD; Andrew Abrams, MPH; Julia Finkelstein, MD; Bilal Chughtai, MD

Can Urol Assoc J 2017; 11(11):E421-4. http://dx.doi.org/10.5489/cuaj.4472

 Objective: Evaluate the efficacy of an oral cranberry supplement on CA-UTIs over a six-month period.

Materials and Methods:  Subjects with long-term indwelling catheters and recurrent symptomatic CA-UTIs were enrolled to take a once-daily oral cranberry supplement with 36 mg proanthocyanidin (PACs) for six months. Primary outcome was reducing the number of symptomatic CA-UTIs. This was defined by ≥103 (cfu)/mL of ≥1 bacterial species in a single catheter urine specimen and signs and symptoms compatible with CA-UTI. Secondary outcomes included bacterial counts and resistance patterns to antibiotics.

Summary: 22 patients with long-term indwelling catheters & recurrent symptomatic CA-UTIs were evaluated (defined by ≥ 103 (cfu)/mL of ≥ 1 bacterial species in a single catheter urine specimen and 2 UTIs in the previous 6 months).  In patients taking once daily consumption of 36 mg PACs for 6 months, no UTIs were reported over the 6 months and no adverse events reported.  A 28% reduction of antibiotic resistances was also noted, with the greatest resistance among tetracycline, levofloxacin and cefazolin.

PACs and UTIs: Human Trial #4

Cranberry syrup vs trimethoprim in the prophylaxis of recurrent urinary tract infections among children: a controlled trial

Jose Uberos, Mercedes Nogueras-Ocana, Verónica Fernandez-Puentes, Rocio Rodriguez-Belmonte, Eduardo Narbona-López, Antonio Molina-Carballo, Antonio Munoz-Hoyos

Journal of Clinical Trials 2012:4 31–38

 Objective: Determine the effectiveness of cranberry syrup in the prophylaxis of recurrent urinary tract infections (UTIs).

Materials and Methods:  A total of 192 patients were recruited. The subjects were aged between 1 month and 13 years. Criteria for inclusion were a background of recurrent UTIs (more than two episodes of infection in the last 6 months), associated or otherwise with vesicoureteral reflux of any degree, or renal pelvic dilatation associated with UTI.  Experimental group was given a nocturnal dose of 0.2 mL/kg of cranberry syrup, just before the evening meal. Control group was given a nocturnal dose of 0.2 mL/kg of a color-masked suspension of trimethoprim at a concentration of 8 mg/mL.

Summary:  Syrup derived from cranberry (with 36 mg PACs in every 5mL dose) was compared to trimethoprim.  Study confirms that proanthocyanidin syrup is safe for pediatrics and is equivalent to trimethoprim in respect to recurrent UTIs. Of the patients recruited with recurrent UTIs, the mean time to infection after taking trimethoprim was 271 days (95% CI: 233–309 days) and after taking cranberry it was 312 days (95% CI: 275–350 days). Logrank (Mantel–Cox) test: 2.14 (P = 0.14).

…36 mg PACs prophylaxis has non-inferiority with respect to trimethoprim in recurrent UTIs.

URIEXO®:

  • Helps prevent Urinary Tract Infections and its symptoms:
    • Painful or difficult urination
    • Frequent urination
    • Urgency to urinate
    • Suprapubic/pelvic pain
  • Two Medicinal Ingredients:
    • D-Mannose (2000 mg/day)
    • PACs, sourced from cranberry (36mg/day)
  • Antibiotic-Free
  • Easy to Swallow Capsules

 

 

 

 


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