Lessons learned during recruitment of a randomized controlled trial for recurrent urinary tract infection prevention in postmenopausal women

Lenger S1, Chu C1, Ghetti C1, Meister M1, Sutcliffe S1, Lowder J1

Research Type


Abstract Category

Research Methods / Techniques

Abstract 738
Non Discussion Abstract
Scientific Non Discussion Abstract Session 37
Infection, Urinary Tract Clinical Trial Female
1.Washington University in St. Louis School of Medicine


Hypothesis / aims of study
Although more research is needed to identify effective prevention strategies for recurrent urinary tract infections (rUTIs) in postmenopausal women, rUTI study recruitment can be challenging because of the need to confirm the diagnosis of rUTI (2 culture-proven urinary tract infections in 6 months or 3 in 12 months) before enrollment and excluding the presence of complicated urinary tract infections (UTIs). In our experience, patients are often referred for clinical evaluation based on self-report of frequent UTI symptoms, physician diagnosis and treatment based on patient symptoms or office urinalysis only, inconsistent culture testing, or a combination of these scenarios. To better understand these challenges and to plan for future large-scale randomized controlled trials (RCTs), we conducted a pilot trial of rUTI prevention by randomizing participants on vaginal estrogen therapy to a nutraceutical to determine the rate of and barriers to recruitment of patients referred to a tertiary academic urogynecology practice for evaluation and treatment of rUTIs.
Study design, materials and methods
Inclusion criteria for our pilot RCT were: (a) postmenopausal women with rUTI (at least 2 culture-proven, symptomatic UTIs in 6 months or at least 3 in 12 months), (b) one or more uropathogens with type 1 pili (the target of the nutraceutical), and (c) current use of vaginal estrogen therapy (VET) for at least 4 weeks. Exclusion criteria were: (a) not postmenopausal, (b) daily antibiotic UTI prophylaxis, (c) complicated UTIs (renal tract anomaly, inability to empty bladder due to neurologic causes, or current self or indwelling catheterization), (d) post void residual of 150 mL or greater with void of 150 mL or more, (e) VET contraindication unless approved by the patient’s oncology-care provider, (f) interstitial cystitis/painful bladder syndrome, (g) urothelial cancer, (h) non-English speaking, (i) enrolled in other UTI clinical trial, or (j) current use of the study nutraceutical or Methenamine. Pre-study anticipated RCT recruitment was 10 patients per month. Data from the first 11 months of this ongoing RCT are reported.
281 patients were seen for frequent or recurrent UTIs during the first 11 months of the study (Figures 1 and 2). Monthly totals for new rUTI patients ranged from 14 to 35. Only 40.6% (n=114) of patients referred for rUTI had culture-proven UTI allowing for further screening. Of these women, 78 were not eligible for the RCT because they met one or more exclusion criteria, most commonly incomplete bladder emptying, current self-catheterization, or already using the study nutraceutical or methenamine. Five patients did not meet RCT inclusion criterion (either lacking at least one uropathogen with type 1 pili or absence of VET use). Two patients were unable to consent due to dementia. Out of the remaining 29 RCT eligible patients, 25 (86.2%) enrolled.
Interpretation of results
Most patients that met RCT eligibility criteria enrolled in the study. However, enrollment was low for several reasons. First, over half of women referred to our tertiary care urogynecology practice for rUTIs did not have documentation of rUTIs at their initial visit, precluding their immediate enrollment into the study. This large percentage was unexpected and may reflect either the presence of UTI-like symptoms without infection or incompletely evaluated/documented rUTIs. Although additional research will be necessary to distinguish these two possibilities, both are troubling as they create unnecessary delays in research and patient care. Women with UTI-like symptoms who do not have rUTIs are likely to have been misdiagnosed in the past and/or received inappropriate care, such as antibiotics, for their symptoms. The exact etiology of their symptoms should be determined to better direct their care; education about current diagnosis recommendations and criteria at the referring provider level may be necessary. For instance, women without actual UTIs may benefit from VET for vaginal atrophy, pelvic floor physical therapy for myofascial causes of symptoms, or interstitial cystitis/bladder pain syndrome therapies. Women with UTI-like symptoms who do in fact have rUTIs should receive prompt bacterial cultures to confirm their UTIs and prompt their rUTI care.

A second reason for our low enrollment was the presence of exclusionary diagnoses and characteristics. Although the number of screened patients with culture-proven rUTIs (n=114) was similar to our anticipated number (n=110 or 10 patients/month for 11 months) in the first 11 months of this ongoing RCT, many of the screened patients had one of more exclusionary diagnoses or characteristics, the most common of which were incomplete bladder emptying, current self-catheterization, and use of rUTI preventive agents. Overall, only 8.9% of all referrals were eligible and enrolled.
Concluding message
Although our findings indicate a strong willingness of rUTI patients to participate in prevention research (86% of eligible patients enrolled), they also highlight the large number of women (over half) referred to a tertiary care urogynecology practice for frequent or recurrent UTI symptoms either without supporting evidence of culture-proven UTI or confirmed not to have UTIs. Two important conclusions can be made. First, future research needs to address the patients referred for UTI-like symptoms that do not have UTIs as the cause of their symptoms. Second, patients referred to urogynecology for recurrent UTI without appropriate documentation can create a delay in patient treatment. There is a need for educating referring providers on the importance of urine cultures in patients experiencing frequent UTI symptoms so that the proper evaluation can be performed, the correct diagnosis made, and individualized prevention strategies can be initiated.
Figure 1 Figure 1: RCT recruitment from urogynecology patients referred to a tertiary practice for frequent or recurrent urinary tract infections (UTIs)
Figure 2 Figure 2: Cumulative patients referred for recurrent urinary tract infection (rUTI)
Funding Division funding Clinical Trial Yes Registration Number ClinicalTrials.gov Identifier: NCT03395288 RCT Yes Subjects Human Ethics Committee Institutional Review Board Helsinki Yes Informed Consent Yes