Clinical trial NCT02431897: Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen
Official title: Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pelvic Organ Prolapse
Urogenital Prolapse
Vaginal Vault Prolapse
Cystocele
Uterine Prolapse
Vaginal Prolapse
Pelvic Floor Disorders
Keywords: Pelvic Organ Prolapse
Pelvic Floor Disorders
Therapy, Estrogen Replacement
Estrogens, Conjugated
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: University of Alabama at Birmingham
name: Women and Infants Hospital of Rhode Island
name: Pfizer
First posted: 2015-05-01
Enrollment: 206
Sex: FEMALE
Minimum age (years): 48
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Surgical "Failure" Defined by (i) Anatomic Assessment of Prolapse, (ii) Presence of Bulge Symptoms, and/or (Iii) Retreatment of Prolapse
timeFrame: 12 months
Secondary outcomes:
measure: Condition Specific (i.e. Pelvic Organ Prolapse) Symptom Bother as Measured by Pelvic Floor Distress Inventory-20 (PFDI-20) Questionnaire
timeFrame: 12 months
measure: Condition Specific (i.e. Pelvic Organ Prolapse) Quality of Life as Measured by Pelvic Floor Impact Questionnaire-7 (PFIQ-7)
timeFrame: 12 months
measure: Generic Quality of Life as Measured by SF-12 Questionnaire
timeFrame: 12 months
measure: 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
timeFrame: Time of surgery
measure: 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
timeFrame: 12 months
measure: Urinary Symptoms as Measured by Urinary Subscale Questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire
timeFrame: Time of surgery
measure: Urinary Symptoms as Measured by Urinary Subscale Questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire
timeFrame: 12 months
measure: Sexual Function as Measured by the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR)
timeFrame: Time of surgery
measure: Sexual Function as Measured by the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR)
timeFrame: 12 months
measure: Number of Participants With Adverse Events
timeFrame: 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Providence
country: United States
facility: Women & Infants Hospital of Rhode Island
state: Rhode Island
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: David D Rahn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.