Urinary Tract Infections, Recurrent
Conditions
Brief summary
Several methods are available for use in the prevention of recurrent urinary tract infections (UTIs) over the past few decades. These methods include suppressive antibiotics, estrogen cream, methenamine hippurate, d-mannose, cranberry, probiotics, and vitamin C. Of these, the majority of the literature is in favor of use of suppressive antibiotics for preventing UTIs. However, this data is now about 10 years old. Increasing use of antibiotics over the years has lead to increased resistance of bacteria. In addition, long-term antibiotic use has several adverse effects, some life-threatening. There is recent literature evaluating the use of several of the alternatives to suppressive antibiotics with mixed results. A comparative study of the efficacy of methenamine hippurate to suppressive antibiotics is lacking in the current literature. Several early partly-randomized trials done with methenamine hippurate have shown promising results, but are only as recent as 1987. The primary objective of this prospective, randomized study is to determine whether there is a significant difference in the prevention of recurrent UTIs when given either methenamine hippurate or daily suppressive antibiotics. The secondary objective of this study is to determine how well patients are able to tolerate each of these medications and what adverse effects are observed in a given 1 year time period. The long-term goals of this study are to find an alternative to using suppressive antibiotics, potentially with a lower adverse effect profile and less of the dangers of long term antibiotic use. Finding an alternative to suppressive antibiotics would also tackle the issue of antibiotic resistance.
Detailed description
Hypothesis: The hypothesis of this study is that the group taking trimethoprim will have a lower recurrence rate than those taking methenamine hippurate based on the literature. The investigators aim to identify to what degree that difference is and whether or not it is an acceptable difference given the greater degree of an antibiotic resistance. Objectives: The primary objective of this prospective, randomized study is to determine whether there is a significant difference in the prevention of recurrent UTIs when given either methenamine hippurate or daily suppressive antibiotics independent of vaginal estrogen use. The secondary objective of this study is to determine how well patients are able to tolerate each of these medications and what adverse effects are observed in a 1 year time period. Specific Aims: 1. Identify if there is a differential impact on prevention of recurrent UTIs when treated with either trimethoprim or methenamine hippurate in a 6 and 12 month period. 2. Identify adverse reactions in each group. 3. Determine whether or not estrogen has a more additive effect to trimethoprim or methenamine hippurate in post-menopausal women. 4. Identify how well tolerated the study medications are and whether or not the size of the pills or the frequency of taking them prevents patients from continuing therapy.
Interventions
DRUGTrimethoprim
suppressive antibiotic. Estrogen cream may be prescribed if the patient is post-menopausal (but not as a part of this study).
antiseptic used in the prevention of recurrent UTIs. Estrogen cream may be prescribed if the patient is post-menopausal (but not as a part of this study).
Sponsors
Endeavor Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Patients diagnosed with recurrent urinary tract infections are recruited into this study.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 99 Years
Healthy volunteers
Yes
Inclusion criteria
* recurrent UTI: at least 2 in the past 6 months or 3 in past year (culture positive) * must have been symptomatic with dysuria, urgency, frequency, suprapubic pain, hematuria, malodorous urine * treated for last UTI and negative urine culture on entry into study * English speaking
Exclusion criteria
* pregnancy * urinary tract abnormalities (eg kidney stones) * acute pyelonephritis * renal insufficiency or failure * known allergy to medications * prophylaxis for post-coital recurrent UTIs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Subsequent Infection as Defined From Time of Treatment Initiation to Recurrence of UTI | up to 12 months | Patients will be advised to follow up with any symptoms of a recurrence or at 6 and 12 month intervals if symptom-free. |
| Recurrent UTI | up to 12 months | The number of patient who had a recurrence of UTI within 12 months |
| Number of Infections | up to 12 months | The number of infections at a 12 month follow up time period as defined by symptoms and positive urine culture. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Effects | up to 12 months | The percentage of patients complaining of adverse effects of each medication, including dyspepsia, dysuria, rash, pruritus, nausea, epigastric pain, vomiting, glossitis, taste changes, fever, and photosensitivity. |
| Morisky Medication Adherence Survey | up to 12 months | Morisky Medication Adherence Scale-8 (MMAS-8). Patient tolerability of medications using a tolerability survey. Minimum and maximum scores are 0 and 8 respectively. 0 means no adherence and 8 is maximal adherence. Low adherence corresponds to a score less than 6, medium adherence is between 6 and \<8, and 8 is high adherence. |
| Bacterial Infection Prevalence and Types | up to 12 months | Urine cultures and sensitivities for positive urine cultures |
Countries
United States
Participant flow
Recruitment details
104 patients actually signed consent to participate but 12 were excluded due to screening failure, decision to decline participation after signing consent, renal failure discovered after enrolling patient, and one unrelated death
Participants by arm
| Arm | Count |
|---|---|
| Patients With Recurrent UTIs Arm 1 Patients are randomized to receive methenamine hippurate in one arm if they are diagnosed with recurrent urinary tract infections.
Methenamine hippurate: antiseptic used in the prevention of recurrent UTIs. Estrogen cream may be prescribed if the patient is post-menopausal (but not as a part of this study). | 47 |
| Patients With Recurrent UTIs Arm 2 Patients are randomized to receive trimethoprim in the other arm if they are diagnosed with recurrent urinary tract infections.
Trimethoprim: suppressive antibiotic. Estrogen cream may be prescribed if the patient is post-menopausal (but not as a part of this study). | 45 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | noncompliant taking medication | 2 | 0 |
Baseline characteristics
| Characteristic | Patients With Recurrent UTIs Arm 2 | Total | Patients With Recurrent UTIs Arm 1 |
|---|---|---|---|
| Age, Continuous | 73 years STANDARD_DEVIATION 10.5 | 72 years STANDARD_DEVIATION 13 | 70 years STANDARD_DEVIATION 15.4 |
| BMI | 30 kg/m2 STANDARD_DEVIATION 7.7 | 30 kg/m2 STANDARD_DEVIATION 6.9 | 30 kg/m2 STANDARD_DEVIATION 6.4 |
| Parity | 2.3 number of births STANDARD_DEVIATION 1.4 | 2.5 number of births STANDARD_DEVIATION 1.9 | 2.7 number of births STANDARD_DEVIATION 2.2 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 45 Participants | 92 Participants | 47 Participants |
| Sex: Female, Male Female | 45 Participants | 92 Participants | 47 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 45 |
| other Total, other adverse events | 6 / 47 | 4 / 45 |
| serious Total, serious adverse events | 0 / 47 | 0 / 45 |
Outcome results
Primary
Number of Infections
The number of infections at a 12 month follow up time period as defined by symptoms and positive urine culture.
Time frame: up to 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Recurrent UTIs Arm 1 | Number of Infections | 1.5 urinary tract infections | Standard Deviation 1.7 |
| Patients With Recurrent UTIs Arm 2 | Number of Infections | 1.6 urinary tract infections | Standard Deviation 1.9 |
Primary
Recurrent UTI
The number of patient who had a recurrence of UTI within 12 months
Time frame: up to 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients With Recurrent UTIs Arm 1 | Recurrent UTI | 28 Participants |
| Patients With Recurrent UTIs Arm 2 | Recurrent UTI | 28 Participants |
Primary
Time to Subsequent Infection as Defined From Time of Treatment Initiation to Recurrence of UTI
Patients will be advised to follow up with any symptoms of a recurrence or at 6 and 12 month intervals if symptom-free.
Time frame: up to 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Recurrent UTIs Arm 1 | Time to Subsequent Infection as Defined From Time of Treatment Initiation to Recurrence of UTI | 101 days | Standard Deviation 84.4 |
| Patients With Recurrent UTIs Arm 2 | Time to Subsequent Infection as Defined From Time of Treatment Initiation to Recurrence of UTI | 119 days | Standard Deviation 94 |
Secondary
Adverse Effects
The percentage of patients complaining of adverse effects of each medication, including dyspepsia, dysuria, rash, pruritus, nausea, epigastric pain, vomiting, glossitis, taste changes, fever, and photosensitivity.
Time frame: up to 12 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients With Recurrent UTIs Arm 1 | Adverse Effects | clostridium difficele infection | 1 Participants |
| Patients With Recurrent UTIs Arm 1 | Adverse Effects | abdominal pain | 0 Participants |
| Patients With Recurrent UTIs Arm 1 | Adverse Effects | rash | 2 Participants |
| Patients With Recurrent UTIs Arm 1 | Adverse Effects | kidney stone | 0 Participants |
| Patients With Recurrent UTIs Arm 1 | Adverse Effects | weakness | 2 Participants |
| Patients With Recurrent UTIs Arm 1 | Adverse Effects | no adverse event | 41 Participants |
| Patients With Recurrent UTIs Arm 1 | Adverse Effects | diarrhea | 1 Participants |
| Patients With Recurrent UTIs Arm 2 | Adverse Effects | no adverse event | 41 Participants |
| Patients With Recurrent UTIs Arm 2 | Adverse Effects | diarrhea | 2 Participants |
| Patients With Recurrent UTIs Arm 2 | Adverse Effects | rash | 0 Participants |
| Patients With Recurrent UTIs Arm 2 | Adverse Effects | clostridium difficele infection | 0 Participants |
| Patients With Recurrent UTIs Arm 2 | Adverse Effects | weakness | 0 Participants |
| Patients With Recurrent UTIs Arm 2 | Adverse Effects | abdominal pain | 1 Participants |
| Patients With Recurrent UTIs Arm 2 | Adverse Effects | kidney stone | 1 Participants |
Secondary
Bacterial Infection Prevalence and Types
Urine cultures and sensitivities for positive urine cultures
Time frame: up to 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Patients With Recurrent UTIs Arm 1 | Bacterial Infection Prevalence and Types | Escherichia coli | 43 infections |
| Patients With Recurrent UTIs Arm 1 | Bacterial Infection Prevalence and Types | Enterococcus faecalis | 3 infections |
| Patients With Recurrent UTIs Arm 1 | Bacterial Infection Prevalence and Types | Strains pan sensitive to all antibiotics | 5 infections |
| Patients With Recurrent UTIs Arm 1 | Bacterial Infection Prevalence and Types | Klebsiella pneumonia | 11 infections |
| Patients With Recurrent UTIs Arm 1 | Bacterial Infection Prevalence and Types | Strains resistant to trimethoprim | 58 infections |
| Patients With Recurrent UTIs Arm 1 | Bacterial Infection Prevalence and Types | Extended spectrum beta lactamase Escherichia coli | 6 infections |
| Patients With Recurrent UTIs Arm 1 | Bacterial Infection Prevalence and Types | Strains resistant to abx other than trimethoprim | 10 infections |
| Patients With Recurrent UTIs Arm 1 | Bacterial Infection Prevalence and Types | Other bacteria | 15 infections |
| Patients With Recurrent UTIs Arm 2 | Bacterial Infection Prevalence and Types | Strains resistant to abx other than trimethoprim | 29 infections |
| Patients With Recurrent UTIs Arm 2 | Bacterial Infection Prevalence and Types | Escherichia coli | 50 infections |
| Patients With Recurrent UTIs Arm 2 | Bacterial Infection Prevalence and Types | Klebsiella pneumonia | 6 infections |
| Patients With Recurrent UTIs Arm 2 | Bacterial Infection Prevalence and Types | Enterococcus faecalis | 9 infections |
| Patients With Recurrent UTIs Arm 2 | Bacterial Infection Prevalence and Types | Extended spectrum beta lactamase Escherichia coli | 9 infections |
| Patients With Recurrent UTIs Arm 2 | Bacterial Infection Prevalence and Types | Other bacteria | 12 infections |
| Patients With Recurrent UTIs Arm 2 | Bacterial Infection Prevalence and Types | Strains pan sensitive to all antibiotics | 20 infections |
| Patients With Recurrent UTIs Arm 2 | Bacterial Infection Prevalence and Types | Strains resistant to trimethoprim | 30 infections |
Secondary
Morisky Medication Adherence Survey
Morisky Medication Adherence Scale-8 (MMAS-8). Patient tolerability of medications using a tolerability survey. Minimum and maximum scores are 0 and 8 respectively. 0 means no adherence and 8 is maximal adherence. Low adherence corresponds to a score less than 6, medium adherence is between 6 and \<8, and 8 is high adherence.
Time frame: up to 12 months
Population: We were not able to obtain the Morisky medication survey on all participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Recurrent UTIs Arm 1 | Morisky Medication Adherence Survey | 7.28 units on a scale | Standard Deviation 1.1 |
| Patients With Recurrent UTIs Arm 2 | Morisky Medication Adherence Survey | 6.94 units on a scale | Standard Deviation 1.6 |