Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen

Pelvic Organ Prolapse Clinical Trial

— IMPROVE  

Official title:

Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02431897
• Other study ID #: STU 022015-117
• Status: Completed
• Phase: Phase 4
• Start date: December 2016
• Est. completion date: May 17, 2023

Study information

• Verified date: August 2023
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a double-blind randomized trial of intravaginal estrogen (conjugated estrogens, 0.625mg/1g cream) vs. placebo in postmenopausal women (up to n=222 enrolled and randomized in order for 188 to undergo surgery) 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: May 17, 2023
• Est. primary completion date: November 29, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 48 Years and older

Eligibility

Inclusion Criteria:

• 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

• Contraindications to estrogen therapy (e.g. spontaneous DVT, stroke, breast or endometrial/ hormone-responsive cancer, genital bleeding of unknown cause)

• 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

Related Conditions & MeSH terms

• Cystocele
• Pelvic Floor Disorders
• Pelvic Organ Prolapse
• Prolapse
• Recurrence
• Urogenital Prolapse
• Uterine Prolapse
• Vaginal Prolapse
• Vaginal Vault Prolapse

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Women & Infants Hospital of Rhode Island	Providence	Rhode Island

Sponsors (4)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	Pfizer, University of Alabama at Birmingham, Women and Infants Hospital of Rhode Island

Country where clinical trial is conducted

United States, 

References & Publications (1)

Rahn DD, Richter HE, Sung VW, Larsen WI, Hynan LS. Design of a Randomized Clinical Trial of Perioperative Vaginal Estrogen Versus Placebo With Transvaginal Native Tissue Apical Prolapse Repair (Investigation to Minimize Prolapse Recurrence of the Vagina using Estrogen: IMPROVE). Female Pelvic Med Reconstr Surg. 2021 Jan 1;27(1):e227-e233. doi: 10.1097/SPV.0000000000000899. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Surgical "Failure" Defined by (i) Anatomic Assessment of Prolapse, (ii) Presence of Bulge Symptoms, and/or (Iii) Retreatment of Prolapse	Cumulative failures, as measured by (i) anatomic assessment of prolapse, (ii) presence of bulge symptoms, and/or (iii) retreatment of pelvic organ prolapse	12 months
Secondary	Condition Specific (i.e. Pelvic Organ Prolapse) Symptom Bother as Measured by Pelvic Floor Distress Inventory-20 (PFDI-20) Questionnaire	Questionnaire 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)	12 months
Secondary	Condition Specific (i.e. Pelvic Organ Prolapse) Quality of Life as Measured by Pelvic Floor Impact Questionnaire-7 (PFIQ-7)	Questionnaire 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)	12 months
Secondary	Generic Quality of Life as Measured by SF-12 Questionnaire	Generic (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.	12 months
Secondary	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	Urinary 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.	Time of surgery
Secondary	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	Urinary 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.	12 months
Secondary	Urinary Symptoms as Measured by Urinary Subscale Questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire	Urinary 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.	Time of surgery
Secondary	Urinary Symptoms as Measured by Urinary Subscale Questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire	Urinary 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.	12 months
Secondary	Sexual Function as Measured by the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR)	Sexual 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.	Time of surgery
Secondary	Sexual Function as Measured by the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR)	Sexual 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.	12 months
Secondary	Number of Participants With Adverse Events	Number of participants reporting any adverse events from baseline randomization to 12 months postoperatively	12 months