IMPROVE: Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen
Study Details
Study Description
Brief Summary
This study randomizes postmenopausal women with symptomatic pelvic organ prolapse planning native tissue transvaginal surgical repair to 6-8 weeks of preoperative and 1-year continued postoperative vaginal estrogen cream compared to placebo cream. This clinical trial and basic science investigation are designed to understand the mechanisms by which local estrogen treatment affects connective tissues of the pelvic floor and determine whether its use before and after prolapse repair will (i) improve success rates of the surgical intervention and minimize prolapse recurrence and (ii) impact favorably upon symptoms of other pelvic floor disorders.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
This is a double-blind randomized trial of intravaginal estrogen (conjugated estrogens, 0.625mg/1g cream) vs. placebo in postmenopausal women (n=222 total) with symptomatic prolapse beyond the hymen planning transvaginal native tissue repairs. Medication will be started >5 weeks before surgery and continued for 1 year postoperatively, i.e. until scar remodeling is complete. The investigators aim to determine if pre- and postoperative intravaginal estrogen therapy (i) results in anatomic and patient-reported subjective improvement in pelvic organ support, and (ii) impacts other pelvic floor disorders (overactive bladder and incontinence, sexual function and pain, postoperative cystitis), satisfaction, quality of life, and vaginal wound healing. Finally, (iii) the investigators will determine the potential mechanisms by which local estrogen treatment alters pelvic organ support by examining full-thickness vaginal wall biopsies taken at the time of surgery for histologic, connective tissue, and smooth muscle synthesis and degradative changes. The investigators expect this will highlight other novel targets for future therapies in prolapse repair and prevention.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Estrogen Cream
|
Drug: 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.
Other Names:
|
| Placebo Comparator: Placebo Cream
|
Drug: 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.
|
Outcome Measures
Primary Outcome Measures
- Surgical "success" or "failure" defined by (i) anatomic assessment of prolapse, (ii) presence or absence of bulge symptoms, (iii) retreatment of prolapse [12 months]
Secondary Outcome Measures
- Condition specific (i.e. pelvic organ prolapse) quality of life as measured by Pelvic Floor Distress Inventory-20 (PFDI-20) questionnaire [Baseline, 12 months]
Change in questionnaire scores from baseline to 12 months
- Condition specific (i.e. pelvic organ prolapse) quality of life as measured by Pelvic Floor Impact Questionnaire-7 (PFIQ-7) [Baseline, 12 months]
Change in questionnaire scores from baseline to 12 months
- Generic quality of life as measured by SF-12 questionnaire [Baseline, 12 months]
Change in questionnaire scores from baseline to 12 months
- 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 [Baseline, time of surgery (8 wk)]
Change in questionnaire scores from baseline to time of 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 [Baseline, 12 months]
Change in questionnaire scores from baseline to 12 months
- Urinary symptoms as measured by urinary subscale questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire [Baseline, time of surgery (8 wk)]
Change in questionnaire scores from baseline to time of surgery
- Urinary symptoms as measured by urinary subscale questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire [Baseline, 12 months]
Change in questionnaire scores from baseline to 12 months
- Sexual function as measured by the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) [Baseline, time of surgery (8 wk)]
Change in questionnaire scores from baseline to time of surgery
- Sexual function as measured by the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) [Baseline, 12 months]
Change in questionnaire scores from baseline to 12 months
- Number of participants with adverse events [through 12 months]
Comparison of proportions by treatment group
Eligibility Criteria
Criteria
Inclusion Criteria:
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Postmenopausal: no menses for >1 year
-
Minimum age: 48 years
-
Symptomatic apical and/or anterior vaginal wall prolapse, stage 2 or greater
-
No estrogen replacement within the last month (may come off current treatment, i.e. wash out, to join the study)
-
Medically fit for elective surgery
-
Physically able to apply/insert the study drug
-
Available for clinic follow-up for minimum 1yr
Exclusion Criteria:
-
Concurrent use of steroid creams for other indications (e.g. lichen sclerosis)
-
BMI >35 kg/m2
-
Recent history (within last month) of vaginal infection or vaginitis
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Contraindications to estrogen therapy (e.g. spontaneous DVT, stroke, breast or endometrial/ hormone-responsive cancer, genital bleeding of unknown cause)
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History of connective tissue disease
-
Any oral or transdermal estrogen, SERM, or other medication impacting vaginal milieu
-
History of vaginal irradiation
-
Allergy to Premarin or its constituents
-
Prior apical repair or use of mesh for prolapse repair
-
Current tobacco use
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35249 |
| 2 | Women & Infants Hospital of Rhode Island | Providence | Rhode Island | United States | 02905 |
| 3 | University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390 |
Sponsors and Collaborators
- University of Texas Southwestern Medical Center
- University of Alabama at Birmingham
- Women and Infants Hospital of Rhode Island
- Pfizer
Investigators
- Principal Investigator: David D Rahn, MD, University of Texas Southwestern Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
- STU 022015-117