Trial Outcomes & Findings for Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen (NCT NCT02431897)
NCT ID: NCT02431897
Last Updated: 2023-09-06
Results Overview
Cumulative failures, as measured by (i) anatomic assessment of prolapse, (ii) presence of bulge symptoms, and/or (iii) retreatment of pelvic organ prolapse
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
206 participants
Primary outcome timeframe
12 months
Results posted on
2023-09-06
Participant Flow
Of the 206 participants consented/enrolled, 7 were not randomized: 4 withdrew consent before randomization, and 3 were found to be ineligible and were not randomized. This left n=199 for randomization.
Participant milestones
| Measure |
Estrogen Cream
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
|---|---|---|
|
Overall Study
STARTED
|
102
|
97
|
|
Overall Study
COMPLETED
|
93
|
93
|
|
Overall Study
NOT COMPLETED
|
9
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen
Baseline characteristics by cohort
| Measure |
Estrogen Cream
n=102 Participants
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
n=97 Participants
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Total
n=199 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.9 years
STANDARD_DEVIATION 6.1 • n=93 Participants
|
65.2 years
STANDARD_DEVIATION 7.3 • n=4 Participants
|
65.0 years
STANDARD_DEVIATION 6.6 • n=27 Participants
|
|
Sex: Female, Male
Female
|
102 Participants
n=93 Participants
|
97 Participants
n=4 Participants
|
199 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
24 Participants
n=93 Participants
|
24 Participants
n=4 Participants
|
48 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
78 Participants
n=93 Participants
|
73 Participants
n=4 Participants
|
151 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
92 Participants
n=93 Participants
|
89 Participants
n=4 Participants
|
181 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Gravidity
|
3 pregnancies
n=93 Participants
|
2 pregnancies
n=4 Participants
|
3 pregnancies
n=27 Participants
|
|
Vaginal deliveries
|
2 births
n=93 Participants
|
2 births
n=4 Participants
|
2 births
n=27 Participants
|
PRIMARY outcome
Timeframe: 12 monthsCumulative failures, as measured by (i) anatomic assessment of prolapse, (ii) presence of bulge symptoms, and/or (iii) retreatment of pelvic organ prolapse
Outcome measures
| Measure |
Estrogen Cream
n=93 Participants
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
n=93 Participants
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
|---|---|---|
|
Surgical "Failure" Defined by (i) Anatomic Assessment of Prolapse, (ii) Presence of Bulge Symptoms, and/or (Iii) Retreatment of Prolapse
|
18 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: 12 monthsQuestionnaire score at 12 months in overall condition-specific symptom bother as measured by Pelvic Floor Distress Inventory-20 (PFDI-20) questionnaire, which is scored from 0-300, higher scores being worse (i.e., more distressing)
Outcome measures
| Measure |
Estrogen Cream
n=93 Participants
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
n=93 Participants
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
|---|---|---|
|
Condition Specific (i.e. Pelvic Organ Prolapse) Symptom Bother as Measured by Pelvic Floor Distress Inventory-20 (PFDI-20) Questionnaire
|
23.1 score on a scale
Standard Error 4.6
|
23.1 score on a scale
Standard Error 4.7
|
SECONDARY outcome
Timeframe: 12 monthsQuestionnaire score at 12 months in overall condition-specific quality of life as measured by Pelvic Floor Impact Questionnaire-7 (PFIQ-7) questionnaire, which is scored from 0-300, higher scores being worse (i.e., more distressing)
Outcome measures
| Measure |
Estrogen Cream
n=93 Participants
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
n=93 Participants
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
|---|---|---|
|
Condition Specific (i.e. Pelvic Organ Prolapse) Quality of Life as Measured by Pelvic Floor Impact Questionnaire-7 (PFIQ-7)
|
8.9 score on a scale
Standard Error 4.5
|
9.5 score on a scale
Standard Error 4.6
|
SECONDARY outcome
Timeframe: 12 monthsGeneric (physical component) quality of life as measured by SF-12 questionnaire at 12 months. Scores range from 0-100, with higher scores indicating better physical functioning; the US population average is 50 points.
Outcome measures
| Measure |
Estrogen Cream
n=93 Participants
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
n=93 Participants
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
|---|---|---|
|
Generic Quality of Life as Measured by SF-12 Questionnaire
|
52.1 score on a scale
Standard Error 0.9
|
53.2 score on a scale
Standard Error 0.9
|
SECONDARY outcome
Timeframe: Time of surgeryUrinary symptom bother as measured by urinary subscale questions of the Pelvic Floor Distress Inventory-20 (PFDI-20) questionnaire, i.e. the Urinary Distress Inventory, UDI-6. This is scored from 0-100, with greater scores indicating greater symptom bother.
Outcome measures
| Measure |
Estrogen Cream
n=102 Participants
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
n=97 Participants
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
|---|---|---|
|
Urinary Symptoms as Measured by Urinary Subscale Questions of the Pelvic Floor Distress Inventory-20 (PFDI-20) Questionnaire, i.e. the Urinary Distress Inventory, UDI-6
|
38.2 score on a scale
Standard Error 2.7
|
37.7 score on a scale
Standard Error 2.8
|
SECONDARY outcome
Timeframe: 12 monthsUrinary symptom bother as measured by urinary subscale questions of the Pelvic Floor Distress Inventory-20 (PFDI-20) questionnaire, i.e. the Urinary Distress Inventory, UDI-6. This is scored from 0-100, with greater scores indicating greater symptom bother.
Outcome measures
| Measure |
Estrogen Cream
n=93 Participants
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
n=93 Participants
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
|---|---|---|
|
Urinary Symptoms as Measured by Urinary Subscale Questions of the Pelvic Floor Distress Inventory-20 (PFDI-20) Questionnaire, i.e. the Urinary Distress Inventory, UDI-6
|
9.8 score on a scale
Standard Error 2.1
|
9.2 score on a scale
Standard Error 2.2
|
SECONDARY outcome
Timeframe: Time of surgeryUrinary symptom impact on quality of life as measured by urinary subscale questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire. This is scored from 0-100, with greater scores indicating worse impact on quality of life.
Outcome measures
| Measure |
Estrogen Cream
n=102 Participants
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
n=97 Participants
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
|---|---|---|
|
Urinary Symptoms as Measured by Urinary Subscale Questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire
|
26.9 score on a scale
Standard Error 1.8
|
25.2 score on a scale
Standard Error 1.8
|
SECONDARY outcome
Timeframe: 12 monthsUrinary symptom impact on quality of life as measured by urinary subscale questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire. This is scored from 0-100, with greater scores indicating worse impact on quality of life.
Outcome measures
| Measure |
Estrogen Cream
n=93 Participants
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
n=93 Participants
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
|---|---|---|
|
Urinary Symptoms as Measured by Urinary Subscale Questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire
|
1.2 score on a scale
Standard Error 1.9
|
2.6 score on a scale
Standard Error 1.9
|
SECONDARY outcome
Timeframe: Time of surgerySexual function in sexually-active women as measured by the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR). The score ranges from 1 (worse sexual experience) to 5 (better sexual experience) with midrange scores commonly seen in women with pelvic floor disorders.
Outcome measures
| Measure |
Estrogen Cream
n=102 Participants
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
n=97 Participants
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
|---|---|---|
|
Sexual Function as Measured by the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR)
|
3.13 score on a scale
Standard Error 0.10
|
3.12 score on a scale
Standard Error 0.10
|
SECONDARY outcome
Timeframe: 12 monthsSexual function in sexually-active women as measured by the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR). The score ranges from 1 (worse sexual experience) to 5 (better sexual experience) with midrange scores commonly seen in women with pelvic floor disorders.
Outcome measures
| Measure |
Estrogen Cream
n=93 Participants
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
n=93 Participants
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
|---|---|---|
|
Sexual Function as Measured by the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR)
|
3.55 score on a scale
Standard Error 0.10
|
3.70 score on a scale
Standard Error 0.10
|
SECONDARY outcome
Timeframe: 12 monthsNumber of participants reporting any adverse events from baseline randomization to 12 months postoperatively
Outcome measures
| Measure |
Estrogen Cream
n=102 Participants
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
n=97 Participants
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
|---|---|---|
|
Number of Participants With Adverse Events
|
73 Participants
|
68 Participants
|
Adverse Events
Estrogen Cream
Serious events: 10 serious events
Other events: 56 other events
Deaths: 0 deaths
Placebo Cream
Serious events: 11 serious events
Other events: 51 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Estrogen Cream
n=102 participants at risk
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
n=97 participants at risk
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Trimalleolar fracture, closed
|
2.9%
3/102 • Number of events 3 • From baseline randomization to 12 months postoperatively
|
0.00%
0/97 • From baseline randomization to 12 months postoperatively
|
|
Nervous system disorders
Stroke
|
0.98%
1/102 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
0.00%
0/97 • From baseline randomization to 12 months postoperatively
|
|
Immune system disorders
Anaphylactic shock due to adverse food reaction
|
0.98%
1/102 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
0.00%
0/97 • From baseline randomization to 12 months postoperatively
|
|
Infections and infestations
Sepsis
|
0.98%
1/102 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
2.1%
2/97 • Number of events 2 • From baseline randomization to 12 months postoperatively
|
|
Musculoskeletal and connective tissue disorders
Fractured hip
|
0.98%
1/102 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
0.00%
0/97 • From baseline randomization to 12 months postoperatively
|
|
Infections and infestations
Infection MRSA
|
0.98%
1/102 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
0.00%
0/97 • From baseline randomization to 12 months postoperatively
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Carcinoma breast stage II
|
0.98%
1/102 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
0.00%
0/97 • From baseline randomization to 12 months postoperatively
|
|
Infections and infestations
Pneumonia
|
0.98%
1/102 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
0.00%
0/97 • From baseline randomization to 12 months postoperatively
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial carcinoma
|
0.98%
1/102 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
1.0%
1/97 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
|
Cardiac disorders
Chest pain
|
0.00%
0/102 • From baseline randomization to 12 months postoperatively
|
1.0%
1/97 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/102 • From baseline randomization to 12 months postoperatively
|
2.1%
2/97 • Number of events 3 • From baseline randomization to 12 months postoperatively
|
|
Infections and infestations
Viral infection NOS
|
0.00%
0/102 • From baseline randomization to 12 months postoperatively
|
1.0%
1/97 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
|
Gastrointestinal disorders
Volvulus
|
0.00%
0/102 • From baseline randomization to 12 months postoperatively
|
1.0%
1/97 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
|
Surgical and medical procedures
Bladder injury
|
0.00%
0/102 • From baseline randomization to 12 months postoperatively
|
1.0%
1/97 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.00%
0/102 • From baseline randomization to 12 months postoperatively
|
1.0%
1/97 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
|
Cardiac disorders
Cardiac catheter ablation
|
0.00%
0/102 • From baseline randomization to 12 months postoperatively
|
1.0%
1/97 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
|
Renal and urinary disorders
Stress urinary incontinence
|
0.00%
0/102 • From baseline randomization to 12 months postoperatively
|
1.0%
1/97 • Number of events 1 • From baseline randomization to 12 months postoperatively
|
Other adverse events
| Measure |
Estrogen Cream
n=102 participants at risk
Conjugated Estrogens Cream: 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
Placebo Cream
n=97 participants at risk
Placebo Cream: 1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.
|
|---|---|---|
|
Infections and infestations
Urinary tract infection
|
17.6%
18/102 • Number of events 20 • From baseline randomization to 12 months postoperatively
|
22.7%
22/97 • Number of events 32 • From baseline randomization to 12 months postoperatively
|
|
Infections and infestations
Yeast infection
|
9.8%
10/102 • Number of events 10 • From baseline randomization to 12 months postoperatively
|
6.2%
6/97 • Number of events 6 • From baseline randomization to 12 months postoperatively
|
|
Gastrointestinal disorders
Nausea and vomiting
|
6.9%
7/102 • Number of events 7 • From baseline randomization to 12 months postoperatively
|
6.2%
6/97 • Number of events 6 • From baseline randomization to 12 months postoperatively
|
|
Reproductive system and breast disorders
Dyspareunia
|
5.9%
6/102 • Number of events 6 • From baseline randomization to 12 months postoperatively
|
5.2%
5/97 • Number of events 5 • From baseline randomization to 12 months postoperatively
|
|
Injury, poisoning and procedural complications
Granulation tissue
|
6.9%
7/102 • Number of events 7 • From baseline randomization to 12 months postoperatively
|
3.1%
3/97 • Number of events 3 • From baseline randomization to 12 months postoperatively
|
|
Reproductive system and breast disorders
Vaginal itching
|
5.9%
6/102 • Number of events 6 • From baseline randomization to 12 months postoperatively
|
4.1%
4/97 • Number of events 4 • From baseline randomization to 12 months postoperatively
|
|
Gastrointestinal disorders
Constipation
|
2.9%
3/102 • Number of events 3 • From baseline randomization to 12 months postoperatively
|
5.2%
5/97 • Number of events 5 • From baseline randomization to 12 months postoperatively
|
Additional Information
Dr. David D. Rahn
University of Texas Southwestern Medical Center Dallas
Phone: 12146486430
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place