Trial Outcomes & Findings for Vaginal Estrogen for the Prevention of Recurrent Urinary Tract Infection in Postmenopausal Women (NCT NCT01958073)

NCT ID: NCT01958073

Last Updated: 2020-09-21

Results Overview

The primary purpose of this study is to assess the efficacy of vaginal estrogen versus placebo at 6 months on the prevention of urinary tract infections (UTI) in postmenopausal women with history of recurrent UTI.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

35 participants

Primary outcome timeframe

6 months of the randomized period

Results posted on

2020-09-21

Participant Flow

At the start of the study we began with the intent of 3 groups for analysis, separating the two forms of vaginal estrogen into separate groups and comparing them to a placebo group. Due to difficulties with recruitment, our protocol was amended so that the two vaginal estrogen groups were combined to one vaginal estrogen group compared to placebo.

Participant milestones

Participant milestones
Measure	Conjugated Estrogen Vaginal Cream Conjugated estrogen vaginal cream 0.5g per vagina 2 times weekly Conjugated Estrogen Vaginal Cream	Estradiol Ring Estradiol Ring per vagina every 3 months Estradiol Ring	Placebo Per vagina 0.5g 2 times weekly Placebo	Vaginal Cream Open Label Conjugated estrogen vaginal cream 0.5g per vagina 2 times weekly Conjugated Estrogen Vaginal Cream	Estradiol Ring Open Label Estradiol Ring per vagina every 3 months Estradiol Ring
Randomized Period STARTED	9	9	17	0	0
Randomized Period COMPLETED	7	8	11	0	0
Randomized Period NOT COMPLETED	2	1	6	0	0
Open Label Period STARTED	0	0	0	5	17
Open Label Period COMPLETED	0	0	0	5	17
Open Label Period NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Vaginal Estrogen for the Prevention of Recurrent Urinary Tract Infection in Postmenopausal Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=17 Participants Per vagina 0.5g 2 times weekly Placebo	Vaginal Estrogen n=18 Participants Conjugated estrogen vaginal cream 0.5g per vagina 2 times weekly OR Estradiol Ring per vagina every 3 months	Total n=35 Participants Total of all reporting groups
Age, Continuous	67.5 years STANDARD_DEVIATION 10.47 • n=5 Participants	72.8 years STANDARD_DEVIATION 8.4 • n=7 Participants	70.15 years STANDARD_DEVIATION 9.72 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	18 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	17 participants n=5 Participants	18 participants n=7 Participants	34 participants n=5 Participants
BMI	28.41 kg/m^2 STANDARD_DEVIATION 7.09 • n=5 Participants	30.33 kg/m^2 STANDARD_DEVIATION 9.21 • n=7 Participants	29.37 kg/m^2 STANDARD_DEVIATION 8.15 • n=5 Participants
Number of UTIs in prior 12 months 2	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Number of UTIs in prior 12 months 3	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Number of UTIs in prior 12 months 4	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Number of UTIs in prior 12 months 5	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Number of UTIs in prior 12 months 6	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Smoking Current	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Smoking Former	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Smoking Never	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Marital Status Single	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Marital Status Married	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Marital Status Divorced/Separated	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Marital Status Widowed	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Marital Status Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Education Less than High School	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Education High School/GED	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Education Associates Degree	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Education 4 year college	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Education Graduate School	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Caffeine use	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Prior Pelvic Surgery	9 Participants n=5 Participants	13 Participants n=7 Participants	22 Participants n=5 Participants
Prior Vaginal Estrogen	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Hormone Replacement Therapy Never	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Hormone Replacement Therapy Past	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
Hormone Replacement Therapy Current	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Diabetes	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months of the randomized period

Population: As treated. Vaginal estrogen groups were combined due to a protocol amendment.

Outcome measures

Outcome measures
Measure	Vaginal Estrogen n=15 Participants Conjugated Estrogen Vaginal Cream OR Estradiol Ring	Placebo n=11 Participants Per vagina Placebo	Initial Placebo to Open Label Vaginal Estrogen Those participants initially randomized to placebo, during the period when they went on open label vaginal estrogen.
Occurrence of UTI During Randomization	8 Participants	10 Participants	—

SECONDARY outcome

Timeframe: Assessed at 6 months for 'a'; assessed over 12 months for 'b'

Population: As treated. Vaginal estrogen groups were combined due to a protocol amendment.

1. To assess overall rates of UTI over 6 months in postmenopausal women with history of recurrent UTI receiving vaginal estrogen (ring or cream). 2. To compare rates of UTI between 6 and 12 months of those subjects initially randomized to placebo.

Outcome measures

Outcome measures
Measure	Vaginal Estrogen n=11 Participants Conjugated Estrogen Vaginal Cream OR Estradiol Ring	Placebo n=15 Participants Per vagina Placebo	Initial Placebo to Open Label Vaginal Estrogen n=10 Participants Those participants initially randomized to placebo, during the period when they went on open label vaginal estrogen.
Rates of UTI in Both Randomization Period and Within Placebo When Changed to Open Label Estrogen No UTI	1 Participants	8 Participants	7 Participants
Rates of UTI in Both Randomization Period and Within Placebo When Changed to Open Label Estrogen 1 UTI	7 Participants	3 Participants	2 Participants
Rates of UTI in Both Randomization Period and Within Placebo When Changed to Open Label Estrogen 2 UTI	2 Participants	4 Participants	1 Participants
Rates of UTI in Both Randomization Period and Within Placebo When Changed to Open Label Estrogen 3 UTI	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 6 months of the randomized period

Population: As treated. Vaginal estrogen groups were combined due to a protocol amendment.

To assess the impact of treatment of recurrent UTI with vaginal estrogen on quality of life at 6 months in postmenopausal women with history of recurrent UTI. Female Sexual Function Index. Scale range 2-95. Lower score corresponds to worse functioning.

Outcome measures

Outcome measures
Measure	Vaginal Estrogen n=11 Participants Conjugated Estrogen Vaginal Cream OR Estradiol Ring	Placebo n=15 Participants Per vagina Placebo	Initial Placebo to Open Label Vaginal Estrogen Those participants initially randomized to placebo, during the period when they went on open label vaginal estrogen.
Quality of Life Questionnaire: Female Sexual Function Index	43.45 score on a scale Standard Deviation 27.83	30.64 score on a scale Standard Deviation 29.38	—

SECONDARY outcome

Timeframe: 6 months of the randomized period

Population: as treated, we did not collect data from the placebo group; although vaginal estrogen groups were combined in a protocol amendment for the primary outcome, they were not combined for this secondary outcome looking at compliance

To assess compliance with vaginal estrogen (ring or cream) treatment at 6 months in postmenopausal women with history of recurrent UTI.

Outcome measures

Outcome measures
Measure	Vaginal Estrogen n=7 Participants Conjugated Estrogen Vaginal Cream OR Estradiol Ring	Placebo n=8 Participants Per vagina Placebo	Initial Placebo to Open Label Vaginal Estrogen Those participants initially randomized to placebo, during the period when they went on open label vaginal estrogen.
Compliance During Randomization	4 Participants	8 Participants	—

SECONDARY outcome

Timeframe: 6 months of the randomized period

Population: as treated; although vaginal estrogen groups were combined in a protocol amendment for the primary outcome, they were not combined for this secondary outcome looking at compliance. Compliance was not assessed in placebo which was used as a comparator group for this outcome.

To assess efficacy of vaginal estrogen at 6 months in those compliant with treatment.

Outcome measures

Outcome measures
Measure	Vaginal Estrogen n=4 Participants Conjugated Estrogen Vaginal Cream OR Estradiol Ring	Placebo n=8 Participants Per vagina Placebo	Initial Placebo to Open Label Vaginal Estrogen n=11 Participants Those participants initially randomized to placebo, during the period when they went on open label vaginal estrogen.
Occurrence of UTI in Those Compliant With Treatment During Randomization	3 Participants	5 Participants	10 Participants

SECONDARY outcome

Timeframe: 6 months of the randomized period

Population: As treated. Vaginal estrogen groups were combined due to a protocol amendment.

To assess the impact of treatment of recurrent UTI with vaginal estrogen on quality of life at 6 months in postmenopausal women with history of recurrent UTI. Medical, Epidemiologic, and Social Aspects of Aging Questionnaire (MESA) urinary incontinence questionnaire: stress urinary incontinence subscale. Subscale range 0-27. A higher score indicated more frequent symptoms.

Outcome measures

Outcome measures
Measure	Vaginal Estrogen n=11 Participants Conjugated Estrogen Vaginal Cream OR Estradiol Ring	Placebo n=15 Participants Per vagina Placebo	Initial Placebo to Open Label Vaginal Estrogen Those participants initially randomized to placebo, during the period when they went on open label vaginal estrogen.
Quality of Life Questionnaire: MESA I	7.00 score on a scale Standard Deviation 7.27	9.86 score on a scale Standard Deviation 6.93	—

SECONDARY outcome

Timeframe: 6 months of the randomized period

Population: As treated. Vaginal estrogen groups were combined due to a protocol amendment.

To assess the impact of treatment of recurrent UTI with vaginal estrogen on quality of life at 6 months in postmenopausal women with history of recurrent UTI. Medical, Epidemiologic, and Social Aspects of Aging Questionnaire (MESA) urinary incontinence questionnaire: urgency urinary incontinence subscale. Subscale range 0-18. High score indicates more frequent symptoms.

Outcome measures

Outcome measures
Measure	Vaginal Estrogen n=11 Participants Conjugated Estrogen Vaginal Cream OR Estradiol Ring	Placebo n=15 Participants Per vagina Placebo	Initial Placebo to Open Label Vaginal Estrogen Those participants initially randomized to placebo, during the period when they went on open label vaginal estrogen.
Quality of Life Questionnaire: MESA II	4.82 score on a scale Standard Deviation 5.76	4.79 score on a scale Standard Deviation 3.21	—

SECONDARY outcome

Timeframe: 6 months of the randomized period

Population: As treated. Vaginal estrogen groups were combined due to a protocol amendment.

To assess the impact of treatment of recurrent UTI with vaginal estrogen on quality of life at 6 months in postmenopausal women with history of recurrent UTI. Pelvic Floor Disability Index. Scale range 0-100. Higher score corresponds to increased bother.

Outcome measures

Outcome measures
Measure	Vaginal Estrogen n=11 Participants Conjugated Estrogen Vaginal Cream OR Estradiol Ring	Placebo n=15 Participants Per vagina Placebo	Initial Placebo to Open Label Vaginal Estrogen Those participants initially randomized to placebo, during the period when they went on open label vaginal estrogen.
Quality of Life Questionnaire: Pelvic Floor Disability Index	65.88 score on a scale Standard Deviation 56.29	55.53 score on a scale Standard Deviation 31.76	—

SECONDARY outcome

Timeframe: 6 months of the randomized period

Population: As treated. Vaginal estrogen groups were combined due to a protocol amendment.

To assess the impact of treatment of recurrent UTI with vaginal estrogen on quality of life at 6 months in postmenopausal women with history of recurrent UTI. Pelvic Floor Impact Questionnaire. Scale range 0-300. Higher score corresponds to increasing bother.

Outcome measures

Outcome measures
Measure	Vaginal Estrogen n=11 Participants Conjugated Estrogen Vaginal Cream OR Estradiol Ring	Placebo n=15 Participants Per vagina Placebo	Initial Placebo to Open Label Vaginal Estrogen Those participants initially randomized to placebo, during the period when they went on open label vaginal estrogen.
Quality of Life Questionnaire: Pelvic Floor Impact Questionnaire	22.08 score on a scale Standard Deviation 44.01	9.86 score on a scale Standard Deviation 14.88	—

SECONDARY outcome

Timeframe: 6 months of the randomized period

Population: As treated. Vaginal estrogen groups were combined due to a protocol amendment.

To assess the impact of treatment of recurrent UTI with vaginal estrogen on quality of life at 6 months in postmenopausal women with history of recurrent UTI. Estimated Percentage of Improvement. Scale range 0-100. Higher score corresponds to more improvement.

Outcome measures

Outcome measures
Measure	Vaginal Estrogen n=11 Participants Conjugated Estrogen Vaginal Cream OR Estradiol Ring	Placebo n=15 Participants Per vagina Placebo	Initial Placebo to Open Label Vaginal Estrogen Those participants initially randomized to placebo, during the period when they went on open label vaginal estrogen.
Quality of Life Questionnaire: Estimated Percentage of Improvement	33.00 percentage of improvement Standard Deviation 35.48	74.64 percentage of improvement Standard Deviation 25.83	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Vaginal Estrogen Cream Randomization

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Vaginal Estrogen Ring Randomization

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Vaginal Estrogen Cream Open Label

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Vaginal Estrogen Ring Open Label

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Kimberly Ferrante

Kaiser Permanente San Diego

Phone: 6199801439

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place