Ignite Creation Date:
2024-05-05 @ 4:44 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00305227
Status:
COMPLETED
Last Update Posted:
2023-04-14
First Post:
2006-03-20
Brief Title:
Intravaginal LACTIN-V for Prevention of Recurrent Urinary Tract Infection
Sponsor:
University of Washington
Organization:
University of Washington
Study Overview
Official Title:
Intravaginal LACTIN-V for Prevention of Recurrent Urinary Tract Infections
Status:
COMPLETED
Status Verified Date:
2023-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Recurrent urinary tract infections RUTIS continue to be a major health problem in women and are now complicated by increasing antibiotic resistance New preventive approaches are needed Because most women with RUTI lack the normal protective Lactobacillus LB in their vaginal flora we hypothesized that restoration of LB would reduce RUTIS In this trail women with recent UTI are randomized to receive either LB or placebo vaginal capsules and are followed for side effects for colonization with LB and for occurrence of RUTI over hte next four months
Detailed Description:
Purpose The purpose of this study is to evaluate the safety of the vaginal suppository LACTIN-V Lactobacillus crispatus CTV-05 as well as the efficacy of LACTIN-V use in preventing recurrent urinary tract infections RUTI in women Study subjects will include pre-menopausal women with a history of frequent RUTI As part of this study we will also evaluate growth of lactobacilli and urinary tract infectionUTI-causing bacteria in the vaginas of women following use of LACTIN-V
Rationale LACTIN-V is composed of L crispatus L crispatus is a bacteria found to grow naturally in the vaginas of healthy women It is felt to be important in preventing vaginal infection and UTI With regard to prevention of UTI L crispatus is thought to prevent the growth of UTI-causing bacteria such as E coli in the vagina and so prevent these UTI-causing bacteria from being able to enter the female urethra and cause infection in the bladder cystitis There is epidemiologic evidence to support this prevention mechanism as absence of L crispatus and related lactobacilli from the vagina has been associated with vaginal E coli growth and with UTI Scientific evidence supports the ability of lactobacilli to prevent vaginal E coli growth by out-competing E coli in vaginal colonization and through the production of toxins such as lactic acid hydrogen peroxide and bacteriocins
LACTIN-V contains a specific strain of L crispatus CTV-05 which was isolated from the vagina of a healthy woman It was prepared as a vaginal suppository with the purpose of restoring growth of healthy L crispatus in the vaginas of women who experience frequent RUTI As indicated above these women often have a deficiency of healthy vaginal lactobacilli growth and therefore may not experience the protective function of these natural organisms It is hoped that use of LACTIN-V will lead to vaginal growth of protective lactobacilli in these women wich will in turn prevent the vaginal growth of E coli and other UTI-causing bacteria Phase 1 and 2 studies of LACTIN-V to date have shown this probiotic to be safe and well tolerated
The impetus for this study is the urgent need for non-antibiotic strategies to prevent UTI UTI is one of the most common bacterial infections It leads to substantial morbidity and health care costs Frequent use of antibiotics for treatment of and prophylaxis against UTI is contributing to the prevalence of antibiotic resistant bacteria which are also making it more difficult to treat UTI Therefore the potential advantage of LACTIN-V is that it is a natural product that may prevent UTI without the use of antibiotics If it proves to be efficacious it could decrease the morbidity and health care costs associated with UTI as well as decrease overall antibiotic use and the corresponding prevalence of antibiotic resistance among UTI-causing bacteria
Primary Objective The primary objective is to evaluate the safety of LACTIN-V compared to placebo in pre-menopausal women with recurrent uncomplicated UTI
Secondary objectives
1 To evaluate the efficacy of LACTIN-V compared to placebo in reducing the incidence of Symptomatic and Probable UTI defined below
2 To evaluate the efficacy of LACTIN-V compared to placebo in decreasing the time to recurrence of Symptomatic and Probable UTI
3 To evaluate the efficacy of LACTIN-V compared to placebo in reducing the prevalence of Asymptomatic UTI defined below
4 To evaluate vaginal growth of CTV-05 in subjects using LACTIN-V compared to placebo
5 To evaluate vaginal growth of lactobacilli in subjects using LACTIN-V compared to subjects using placebo
6 To evaluate vaginal growth of E coli in subjects using LACTIN-V compared to subjects using placebo
Case Definitions
Symptomatic UTI One or more UTI symptoms dysuria urgency frequency suprapubic pain flank pain with a positive urine culture In symptomatic subjects a positive urine culture is defined as 102ml of an UTI-causing bacteria UTI episodes will be recorded as Symptomatic UTI if a negative urine culture at Visit 2 or at another interim study visit confirms resolution of the prior UTI in order to distinguish a new Symptomatic UTI from a Persistent UTI
Asymptomatic UTI A positive urine culture in a subject who reports no urinary symptoms In asymptomatic subjects a positive urine culture is defined as 105ml of an UTI-causing bacteria UTI episodes will be recorded as Asymptomatic UTI if a negative urine culture at Visit 2 or at another interim study visit confirms resolution of the prior UTI in order to distinguish a new Asymptomatic UTI from a Persistent UTI
Probable UTI One or more UTI symptoms dysuria urgency frequency suprapubic pain flank pain in a subject who contacted a healthcare provider and was treated with antibiotics for a UTI without confirmatory urine culture UTI episodes will be recorded as Probable UTI if a negative urine culture at Visit 2 or at another interim study visit confirms resolution of the prior UTI in order to distinguish a new Probable UTI from a Persistent UTI
Persistent UTI A positive urine culture following antibiotic treatment for a UTI
General Procedures This will be a randomized double-blind placebo-controlled trial of LACTIN-V Subjects will include 100 pre-menopausal women with a history of frequent RUTI who are currently or recently being treated for a symptomatic UTI with trimethoprim-sulfamethoxazole Trimethoprim-sulfamethoxazole is one of several antibiotics considered standard-of-care for treatment of symptomatic UTI Subjects will be randomized such that 50 women will receive LACTIN-V at a dose of 5x108 CFUsuppository and 50 women will receive placebo LACTIN-V and placebo are to be taken once per day for five days during the first week of use followed by once per week for 10 weeks on Days 8 15 22 29 36 43 50 57 64 and 71 for a total of 15 doses over 11 weeks Subjects will undergo five scheduled visits and receive two telephone calls
Visit 1 is the Screening Visit This visit will take place during or soon after evaluation for a symptomatic UTI The following will occur during Visit 1 informed consent review of eligibility history physical exam pelvic exam Pap smear urine pregnancy test and screening tests for gonorrhea chlamydia bacterial vaginosis yeast and trichomonas Subjects will provide urine samples for microscopic analysis dipstick analysis culture and antibiotic susceptibility testing and vaginal fluid specimens for laboratory assessment of vaginal growth of lactobacilli including CTV-05
Visit 2 is the Randomization Visit and represents Week 1 of the study Visit 2 will take place 3-10 days after completion of antibiotic therapy for UTI Subjects will have their eligibility confirmed and undergo a focused pelvic exam without speculum or bimanual exam unless clinically indicated have a screening test for bacterial vaginosis yeast and trichomonas and have a repeat pregnancy test Subjects will also provide urine and vaginal fluid specimens as in Visit 1 Subjects will then be randomized to LACTIN-V or placebo Subjects will place the first suppository under supervision and will be instructed to use a 7-day study calendar to record study product use and related symptoms during the first week and to use a 10-week study calendar to record study product use and related symptoms thereafter
Day 4-7 phone call The purpose of this phone call is to assess use of the study product as well as any associated symptoms
Visit 3 will occur during Week 2 days 8-14 following randomization Subjects will be asked about study product use adverse events and symptoms Subjects will undergo focused physical and pelvic exams without speculum or bimanual exam unless clinically indicated Subjects will have a screening test for bacterial vaginosis and provide urine and vaginal fluid specimens as before
Visit 4 will occur during Week 11 and will be similar to Visit 3
Visit 5 will occur during Week 16 The procedures for Visit 5 will be similar to those of Visits 3 and 4 However during this visit subjects will undergo a complete pelvic exam including speculum and bimanual exams and undergo a repeat pregnancy test
9 Month telephone call The purpose of this phone call is to assess the occurrence of adverse events symptoms of UTI new UTI or other medical diagnosesand pregnancy
In addition to the above schedules visits subjects will be asked to come to the research clinic for Unscheduled Visits if they experience any adverse events or new symptoms of UTI During these unscheduled visits subjects will undergo history physical and complete pelvic exams screening tests for bacterial vaginosis yeast and trichomonas as well as for other sexually transmitted diseases as clinically indicated Subjects will provide urine samples for microscopic analysis dipstick analysis culture and antibiotic susceptibility testing Subjects will provide vaginal fluid samples for assessment of CTV-05 lactobacillus and E coli growth
Subjects diagnosed with a Symptomatic UTI during the study will be treated with an antibiotic They will then be asked to return to the study clinic for a follow-up urine culture two weeks later to confirm UTI resolution
Laboratory procedures will include
wet mount slides of vaginal fluid all Visits
urine dipstick testing all Visits
urine pregnancy testing Visits 1 2 and 5
Pap smear Visit 1
Testing for gonorrhea and chlamydia by culture Visit 1 other visits as indicated
urinalysis all Visits
urine culture all Visits
gram stain and culture of vaginal fluid specimens All Visits
Rep-PCR for CTV-05 Visits 2-5
DNA amplification of vaginal flora all Visits
Statistical Analysis The primary cohort for analysis will be the intent-to-treat ITT cohort The ITT cohort is defined as subjects who are randomized in the study Other cohorts to be evaluated will include the modified ITT Evaluable and according-to-protocol cohorts
Rationale LACTIN-V is composed of L crispatus L crispatus is a bacteria found to grow naturally in the vaginas of healthy women It is felt to be important in preventing vaginal infection and UTI With regard to prevention of UTI L crispatus is thought to prevent the growth of UTI-causing bacteria such as E coli in the vagina and so prevent these UTI-causing bacteria from being able to enter the female urethra and cause infection in the bladder cystitis There is epidemiologic evidence to support this prevention mechanism as absence of L crispatus and related lactobacilli from the vagina has been associated with vaginal E coli growth and with UTI Scientific evidence supports the ability of lactobacilli to prevent vaginal E coli growth by out-competing E coli in vaginal colonization and through the production of toxins such as lactic acid hydrogen peroxide and bacteriocins
LACTIN-V contains a specific strain of L crispatus CTV-05 which was isolated from the vagina of a healthy woman It was prepared as a vaginal suppository with the purpose of restoring growth of healthy L crispatus in the vaginas of women who experience frequent RUTI As indicated above these women often have a deficiency of healthy vaginal lactobacilli growth and therefore may not experience the protective function of these natural organisms It is hoped that use of LACTIN-V will lead to vaginal growth of protective lactobacilli in these women wich will in turn prevent the vaginal growth of E coli and other UTI-causing bacteria Phase 1 and 2 studies of LACTIN-V to date have shown this probiotic to be safe and well tolerated
The impetus for this study is the urgent need for non-antibiotic strategies to prevent UTI UTI is one of the most common bacterial infections It leads to substantial morbidity and health care costs Frequent use of antibiotics for treatment of and prophylaxis against UTI is contributing to the prevalence of antibiotic resistant bacteria which are also making it more difficult to treat UTI Therefore the potential advantage of LACTIN-V is that it is a natural product that may prevent UTI without the use of antibiotics If it proves to be efficacious it could decrease the morbidity and health care costs associated with UTI as well as decrease overall antibiotic use and the corresponding prevalence of antibiotic resistance among UTI-causing bacteria
Primary Objective The primary objective is to evaluate the safety of LACTIN-V compared to placebo in pre-menopausal women with recurrent uncomplicated UTI
Secondary objectives
1 To evaluate the efficacy of LACTIN-V compared to placebo in reducing the incidence of Symptomatic and Probable UTI defined below
2 To evaluate the efficacy of LACTIN-V compared to placebo in decreasing the time to recurrence of Symptomatic and Probable UTI
3 To evaluate the efficacy of LACTIN-V compared to placebo in reducing the prevalence of Asymptomatic UTI defined below
4 To evaluate vaginal growth of CTV-05 in subjects using LACTIN-V compared to placebo
5 To evaluate vaginal growth of lactobacilli in subjects using LACTIN-V compared to subjects using placebo
6 To evaluate vaginal growth of E coli in subjects using LACTIN-V compared to subjects using placebo
Case Definitions
Symptomatic UTI One or more UTI symptoms dysuria urgency frequency suprapubic pain flank pain with a positive urine culture In symptomatic subjects a positive urine culture is defined as 102ml of an UTI-causing bacteria UTI episodes will be recorded as Symptomatic UTI if a negative urine culture at Visit 2 or at another interim study visit confirms resolution of the prior UTI in order to distinguish a new Symptomatic UTI from a Persistent UTI
Asymptomatic UTI A positive urine culture in a subject who reports no urinary symptoms In asymptomatic subjects a positive urine culture is defined as 105ml of an UTI-causing bacteria UTI episodes will be recorded as Asymptomatic UTI if a negative urine culture at Visit 2 or at another interim study visit confirms resolution of the prior UTI in order to distinguish a new Asymptomatic UTI from a Persistent UTI
Probable UTI One or more UTI symptoms dysuria urgency frequency suprapubic pain flank pain in a subject who contacted a healthcare provider and was treated with antibiotics for a UTI without confirmatory urine culture UTI episodes will be recorded as Probable UTI if a negative urine culture at Visit 2 or at another interim study visit confirms resolution of the prior UTI in order to distinguish a new Probable UTI from a Persistent UTI
Persistent UTI A positive urine culture following antibiotic treatment for a UTI
General Procedures This will be a randomized double-blind placebo-controlled trial of LACTIN-V Subjects will include 100 pre-menopausal women with a history of frequent RUTI who are currently or recently being treated for a symptomatic UTI with trimethoprim-sulfamethoxazole Trimethoprim-sulfamethoxazole is one of several antibiotics considered standard-of-care for treatment of symptomatic UTI Subjects will be randomized such that 50 women will receive LACTIN-V at a dose of 5x108 CFUsuppository and 50 women will receive placebo LACTIN-V and placebo are to be taken once per day for five days during the first week of use followed by once per week for 10 weeks on Days 8 15 22 29 36 43 50 57 64 and 71 for a total of 15 doses over 11 weeks Subjects will undergo five scheduled visits and receive two telephone calls
Visit 1 is the Screening Visit This visit will take place during or soon after evaluation for a symptomatic UTI The following will occur during Visit 1 informed consent review of eligibility history physical exam pelvic exam Pap smear urine pregnancy test and screening tests for gonorrhea chlamydia bacterial vaginosis yeast and trichomonas Subjects will provide urine samples for microscopic analysis dipstick analysis culture and antibiotic susceptibility testing and vaginal fluid specimens for laboratory assessment of vaginal growth of lactobacilli including CTV-05
Visit 2 is the Randomization Visit and represents Week 1 of the study Visit 2 will take place 3-10 days after completion of antibiotic therapy for UTI Subjects will have their eligibility confirmed and undergo a focused pelvic exam without speculum or bimanual exam unless clinically indicated have a screening test for bacterial vaginosis yeast and trichomonas and have a repeat pregnancy test Subjects will also provide urine and vaginal fluid specimens as in Visit 1 Subjects will then be randomized to LACTIN-V or placebo Subjects will place the first suppository under supervision and will be instructed to use a 7-day study calendar to record study product use and related symptoms during the first week and to use a 10-week study calendar to record study product use and related symptoms thereafter
Day 4-7 phone call The purpose of this phone call is to assess use of the study product as well as any associated symptoms
Visit 3 will occur during Week 2 days 8-14 following randomization Subjects will be asked about study product use adverse events and symptoms Subjects will undergo focused physical and pelvic exams without speculum or bimanual exam unless clinically indicated Subjects will have a screening test for bacterial vaginosis and provide urine and vaginal fluid specimens as before
Visit 4 will occur during Week 11 and will be similar to Visit 3
Visit 5 will occur during Week 16 The procedures for Visit 5 will be similar to those of Visits 3 and 4 However during this visit subjects will undergo a complete pelvic exam including speculum and bimanual exams and undergo a repeat pregnancy test
9 Month telephone call The purpose of this phone call is to assess the occurrence of adverse events symptoms of UTI new UTI or other medical diagnosesand pregnancy
In addition to the above schedules visits subjects will be asked to come to the research clinic for Unscheduled Visits if they experience any adverse events or new symptoms of UTI During these unscheduled visits subjects will undergo history physical and complete pelvic exams screening tests for bacterial vaginosis yeast and trichomonas as well as for other sexually transmitted diseases as clinically indicated Subjects will provide urine samples for microscopic analysis dipstick analysis culture and antibiotic susceptibility testing Subjects will provide vaginal fluid samples for assessment of CTV-05 lactobacillus and E coli growth
Subjects diagnosed with a Symptomatic UTI during the study will be treated with an antibiotic They will then be asked to return to the study clinic for a follow-up urine culture two weeks later to confirm UTI resolution
Laboratory procedures will include
wet mount slides of vaginal fluid all Visits
urine dipstick testing all Visits
urine pregnancy testing Visits 1 2 and 5
Pap smear Visit 1
Testing for gonorrhea and chlamydia by culture Visit 1 other visits as indicated
urinalysis all Visits
urine culture all Visits
gram stain and culture of vaginal fluid specimens All Visits
Rep-PCR for CTV-05 Visits 2-5
DNA amplification of vaginal flora all Visits
Statistical Analysis The primary cohort for analysis will be the intent-to-treat ITT cohort The ITT cohort is defined as subjects who are randomized in the study Other cohorts to be evaluated will include the modified ITT Evaluable and according-to-protocol cohorts
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| UWLB-001 | OTHER | University of Washington | httpsreporternihgovquickSearch5P01DK053369 |
| 5P01DK053369 | NIH | None | None |