Ignite Creation Date:
2024-05-06 @ 1:20 PM
Last Modification Date:
2024-10-26 @ 1:12 PM
Study NCT ID:
NCT03996057
Status:
WITHDRAWN
Last Update Posted:
2022-07-08
First Post:
2019-06-17
Brief Title:
Methenamine in a Non-antibiotic Multimodal Approach to UTI Prevention
Sponsor:
Washington University School of Medicine
Organization:
Washington University School of Medicine
Study Overview
Official Title:
The Efficacy and Effect of Methenamine Hippurate in a Non-antibiotic Multimodal Approach to UTI Prevention
Status:
WITHDRAWN
Status Verified Date:
2022-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Project canceled due to PI leaving institution staff changes and COVID
Project canceled for other reason describe - Due to staff changes and COVID
Project canceled due to PI leaving staff changes and COVID
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Urinary tract infections UTIs are the most common bacterial infection and are especially common in postmenopausal women who often experience recurrent UTIs Women with recurrent UTIs are commonly treated with antibiotics but side effects collateral damage to commensal bacteria and antimicrobial resistance result from frequent antibiotic use It is paramount that researchers develop non-antibiotic treatment strategies for UTIs
Several non-antibiotic strategies may be successful in preventing recurrent UTIs in postmenopausal women including low-dose vaginal estrogen d-mannose and methenamine hippurate Methenamine hippurate MH is interesting as it causes few side effects kills bacteria by denaturing bacterial proteins RNA and DNA and does not develop resistance Several studies have demonstrated the efficacy of daily methenamine on the incidence of UTI However women often require multiple therapies in order to prevent recurrence There are currently few guidelines to help clinicians identify optimal treatment regimens for non-antibiotic prevention of UTI
The purpose of this pilot study is to examine the feasibility of developing a sequential multiple assignment randomization trial SMART and examine the treatment effect of MH in combination with vaginal estrogen VET and D-mannose on prevention of UTI The investigators plan to examine the efficacy of the addition of MH to low dose VET and d-mannose in the UTI prevention through randomization to MH VET D-mannose vs continuing VET D-mannose alone The primary outcome will be the proportion of patients who have symptomatic culture-proven UTI during a 3 month treatment period The investigators hypothesize that women on low dose VET d-mannose and MH will be less likely to have recurrent UTI than those with VET and d-mannose alone
This study uses a pragmatic longitudinal approach that mimics patients clinical experiences and physicians decision points during management of UTI prophylaxis Through this randomized controlled pilot study this proposal would allow the investigators to examine the feasibility of conducting a larger-scale adaptive study trial and estimate the treatment effect of a non-antibiotic regimen augmented with MH in women who continue to develop recurrence
Several non-antibiotic strategies may be successful in preventing recurrent UTIs in postmenopausal women including low-dose vaginal estrogen d-mannose and methenamine hippurate Methenamine hippurate MH is interesting as it causes few side effects kills bacteria by denaturing bacterial proteins RNA and DNA and does not develop resistance Several studies have demonstrated the efficacy of daily methenamine on the incidence of UTI However women often require multiple therapies in order to prevent recurrence There are currently few guidelines to help clinicians identify optimal treatment regimens for non-antibiotic prevention of UTI
The purpose of this pilot study is to examine the feasibility of developing a sequential multiple assignment randomization trial SMART and examine the treatment effect of MH in combination with vaginal estrogen VET and D-mannose on prevention of UTI The investigators plan to examine the efficacy of the addition of MH to low dose VET and d-mannose in the UTI prevention through randomization to MH VET D-mannose vs continuing VET D-mannose alone The primary outcome will be the proportion of patients who have symptomatic culture-proven UTI during a 3 month treatment period The investigators hypothesize that women on low dose VET d-mannose and MH will be less likely to have recurrent UTI than those with VET and d-mannose alone
This study uses a pragmatic longitudinal approach that mimics patients clinical experiences and physicians decision points during management of UTI prophylaxis Through this randomized controlled pilot study this proposal would allow the investigators to examine the feasibility of conducting a larger-scale adaptive study trial and estimate the treatment effect of a non-antibiotic regimen augmented with MH in women who continue to develop recurrence
Detailed Description:
Urinary tract infections UTIs are the most common bacterial infection and are especially common in postmenopausal women who often experience recurrent UTIs Women with recurrent UTIs are commonly treated with antibiotics but side effects collateral damage to commensal bacteria and antimicrobial resistance result from frequent antibiotic use The Centers for Disease Control and Prevention estimate that drug resistance contributes to 23000 deaths 2049442 illnesses and 20 billion dollars in excess direct healthcare costs in the United States annually Thus it is paramount that researchers develop non-antibiotic treatment strategies for UTIs
Several non-antibiotic strategies may be successful in preventing recurrent UTIs in postmenopausal women One is low-dose vaginal estrogen which may decrease the rate of recurrent UTIs by decreasing inflammation promoting bladder repair and promoting retention of lactobacilli Another is d-mannose a natural sugar that may decrease bacterial adherence to the urothelium Methenamine hippurate has regained interest recently First it causes few side effects Second it functions by producing formaldehyde in the urine which kills bacteria by denaturing bacterial proteins RNA and DNA Thus far no methenamine-resistant bacteria have been reported to develop in vivo Lastly several studies have demonstrated that 2 grams daily of methenamine reduces the incidence of UTI and is likely comparable to the antibiotic nitrofurantoin for UTI prophylaxis However in the investigators clinical experience women often require multiple therapies in order to prevent recurrence There are currently few guidelines to help clinicians identify optimal treatment regimens for prevention of UTI The clinical challenge is to optimize individual treatment regimens by maximizing efficacy and minimizing the number of medications cost side effects and nonadherence for each individual
The purpose of this pilot study is to 1 examine the feasibility of developing a sequential multiple assignment randomization trial SMART and 2 examine the treatment effect of methenamine hippurate in combination with vaginal estrogen and D-mannose on prevention of UTI This adaptive study design allows the investigators to examine the efficacy of non-antibiotic prophylaxis and initiation of subsequent preventative therapies based on individual responses It is a pragmatic longitudinal approach that mimics patients clinical experiences and physicians decision points during management of UTI prophylaxis Given the efficacy and relative safety of methenamine hippurate the investigators are particularly interested in its efficacy among those who have had suboptimal response to vaginal estrogen and D-mannose The timing of this study is ideal as the investigators are also currently conducting a trial of vaginal estrogen plus D-mannose in postmenopausal women Through this randomized controlled pilot study this proposal would allow the investigators to examine the feasibility of conducting a larger-scale adaptive study trial on the use of methenamine hippurate in combination with vaginal estrogen plus D-mannose and estimate the treatment effect of a non-antibiotic regimen augmented with methenamine hippurate in women who continue to develop recurrence
This study is a planned extension of a previously proposed clinical trial on d-mannose and vaginal estrogen IRB201711120 however any postmenopausal women with a history of recurrent UTI who then develop UTI while on a combined prophylaxis regimen of d-mannose and vaginal estrogen will be eligible for the randomized controlled trial on methenamine augmentation The investigators plan to examine the efficacy of the addition of methenamine hippurate to low dose vaginal estrogen and d-mannose in the UTI prevention through randomization to methenamine vaginal estrogen D-mannose vs continuing vaginal estrogen D-mannose alone Patients will be randomized to either the addition of methenamine hippurate or continuing with vaginal estrogen D-mannose alone The primary outcome will be the proportion of patients who have symptomatic culture-proven UTI during a 3 month treatment period The investigators hypothesize that women on low dose vaginal estrogen d-mannose and methenamine hippurate will be less likely to have recurrent UTI than those with low dose vaginal estrogen and d-mannose alone As part of the study baseline information and vaginal urine and fecal samples may be taken Additionally as part of examining feasibility of a larger study recruitment retention refusal non-compliance and adherence rates will be collected Patients who decline or drop out of the study will be contacted to answer questions on reasons for refusal or withdrawal Subjects who undergo randomization will either add methenamine to their ongoing vaginal estrogen D-mannose or continue on vaginal estrogen D-mannose alone They will receive weekly calls or text reminders to record study diaries and to take their medications Patients will follow up at the end of 3 months at their usual follow up appointment for routine examination questionnaires and urine and possible vaginal and fecal samples Follow up may be extended up to 1 month prior or 6 months afterward their baseline visit 2-6 months after the baseline visit for those who do not make their 3 months appointment The investigators also plan to describe the uropathogen profile and antibiotic resistance of UTIs that occur during prophylaxis with vaginal estrogen d-mannose with or without methenamine hippurate Lastly the investigators hope to examine the impact of a non-antibiotic prophylaxis regimen that includes methenamine hippurate on the bladder microenvironment as well as the urinary vaginal and intestinal microbiomes
Several non-antibiotic strategies may be successful in preventing recurrent UTIs in postmenopausal women One is low-dose vaginal estrogen which may decrease the rate of recurrent UTIs by decreasing inflammation promoting bladder repair and promoting retention of lactobacilli Another is d-mannose a natural sugar that may decrease bacterial adherence to the urothelium Methenamine hippurate has regained interest recently First it causes few side effects Second it functions by producing formaldehyde in the urine which kills bacteria by denaturing bacterial proteins RNA and DNA Thus far no methenamine-resistant bacteria have been reported to develop in vivo Lastly several studies have demonstrated that 2 grams daily of methenamine reduces the incidence of UTI and is likely comparable to the antibiotic nitrofurantoin for UTI prophylaxis However in the investigators clinical experience women often require multiple therapies in order to prevent recurrence There are currently few guidelines to help clinicians identify optimal treatment regimens for prevention of UTI The clinical challenge is to optimize individual treatment regimens by maximizing efficacy and minimizing the number of medications cost side effects and nonadherence for each individual
The purpose of this pilot study is to 1 examine the feasibility of developing a sequential multiple assignment randomization trial SMART and 2 examine the treatment effect of methenamine hippurate in combination with vaginal estrogen and D-mannose on prevention of UTI This adaptive study design allows the investigators to examine the efficacy of non-antibiotic prophylaxis and initiation of subsequent preventative therapies based on individual responses It is a pragmatic longitudinal approach that mimics patients clinical experiences and physicians decision points during management of UTI prophylaxis Given the efficacy and relative safety of methenamine hippurate the investigators are particularly interested in its efficacy among those who have had suboptimal response to vaginal estrogen and D-mannose The timing of this study is ideal as the investigators are also currently conducting a trial of vaginal estrogen plus D-mannose in postmenopausal women Through this randomized controlled pilot study this proposal would allow the investigators to examine the feasibility of conducting a larger-scale adaptive study trial on the use of methenamine hippurate in combination with vaginal estrogen plus D-mannose and estimate the treatment effect of a non-antibiotic regimen augmented with methenamine hippurate in women who continue to develop recurrence
This study is a planned extension of a previously proposed clinical trial on d-mannose and vaginal estrogen IRB201711120 however any postmenopausal women with a history of recurrent UTI who then develop UTI while on a combined prophylaxis regimen of d-mannose and vaginal estrogen will be eligible for the randomized controlled trial on methenamine augmentation The investigators plan to examine the efficacy of the addition of methenamine hippurate to low dose vaginal estrogen and d-mannose in the UTI prevention through randomization to methenamine vaginal estrogen D-mannose vs continuing vaginal estrogen D-mannose alone Patients will be randomized to either the addition of methenamine hippurate or continuing with vaginal estrogen D-mannose alone The primary outcome will be the proportion of patients who have symptomatic culture-proven UTI during a 3 month treatment period The investigators hypothesize that women on low dose vaginal estrogen d-mannose and methenamine hippurate will be less likely to have recurrent UTI than those with low dose vaginal estrogen and d-mannose alone As part of the study baseline information and vaginal urine and fecal samples may be taken Additionally as part of examining feasibility of a larger study recruitment retention refusal non-compliance and adherence rates will be collected Patients who decline or drop out of the study will be contacted to answer questions on reasons for refusal or withdrawal Subjects who undergo randomization will either add methenamine to their ongoing vaginal estrogen D-mannose or continue on vaginal estrogen D-mannose alone They will receive weekly calls or text reminders to record study diaries and to take their medications Patients will follow up at the end of 3 months at their usual follow up appointment for routine examination questionnaires and urine and possible vaginal and fecal samples Follow up may be extended up to 1 month prior or 6 months afterward their baseline visit 2-6 months after the baseline visit for those who do not make their 3 months appointment The investigators also plan to describe the uropathogen profile and antibiotic resistance of UTIs that occur during prophylaxis with vaginal estrogen d-mannose with or without methenamine hippurate Lastly the investigators hope to examine the impact of a non-antibiotic prophylaxis regimen that includes methenamine hippurate on the bladder microenvironment as well as the urinary vaginal and intestinal microbiomes
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None