Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen

NCT02431897 | Completed Phase 4 Results DMC

• 1 other identifier: STU 022015-117
• Study Type: interventional
• Target: 206
• Locations: 1 country
• Sites: 3

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Condition Specific (i.e. Pelvic Organ Prolapse) Symptom Bother as Measured by Pelvic Floor Distress Inventory-20 (PFDI-20) Questionnaire

  12 months

• Condition Specific (i.e. Pelvic Organ Prolapse) Quality of Life as Measured by Pelvic Floor Impact Questionnaire-7 (PFIQ-7)

  12 months

• Generic Quality of Life as Measured by SF-12 Questionnaire

  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

  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

  12 months

Study Arms (2)

Estrogen Cream

EXPERIMENTAL

Conjugated Estrogens cream

Drug: Conjugated Estrogens Cream

Placebo Cream

PLACEBO COMPARATOR

Placebo cream

Drug: Placebo Cream

Interventions

Conjugated Estrogens Cream DRUG

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.

Also known as: Premarin Vaginal Cream

Estrogen Cream

Placebo Cream DRUG

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

Eligibility Criteria

• Age: 48 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• University of Alabama at Birmingham: collaborator
• Women and Infants Hospital of Rhode Island: collaborator
• Pfizer: collaborator

Study Sites (3)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (6)

• 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.

  PMID: 32541299 BACKGROUND

• Rahn DD, Richter HE, Sung VW, Pruszynski JE. Three-year outcomes of a randomized clinical trial of perioperative vaginal estrogen as adjunct to native tissue vaginal apical prolapse repair. Am J Obstet Gynecol. 2024 Aug;231(2):263.e1-263.e10. doi: 10.1016/j.ajog.2024.04.042. Epub 2024 May 4.

  PMID: 38710269 DERIVED

• Rahn DD, Richter HE, Sung VW, Hynan LS, Pruszynski JE. Characteristics Associated With Surgical Failure After Native Tissue Apical Prolapse Repair. Obstet Gynecol. 2024 Feb 1;143(2):312-319. doi: 10.1097/AOG.0000000000005478. Epub 2023 Dec 7.

  PMID: 38061041 DERIVED

• Rahn DD, Richter HE, Sung VW, Pruszynski JE, Hynan LS. Perioperative Vaginal Estrogen as Adjunct to Native Tissue Vaginal Apical Prolapse Repair: A Randomized Clinical Trial. JAMA. 2023 Aug 15;330(7):615-625. doi: 10.1001/jama.2023.12317.

  PMID: 37581673 DERIVED

• Taithongchai A, Johnson EE, Ismail SI, Barron-Millar E, Kernohan A, Thakar R. Oestrogen therapy for treating pelvic organ prolapse in postmenopausal women. Cochrane Database Syst Rev. 2023 Jul 11;7(7):CD014592. doi: 10.1002/14651858.CD014592.pub2.

  PMID: 37431855 DERIVED

• Rahn DD, Richter HE, Sung VW, Hynan LS, Pruszynski JE. Effects of preoperative intravaginal estrogen on pelvic floor disorder symptoms in postmenopausal women with pelvic organ prolapse. Am J Obstet Gynecol. 2023 Sep;229(3):309.e1-309.e10. doi: 10.1016/j.ajog.2023.05.023. Epub 2023 May 25.

  PMID: 37244454 DERIVED

MeSH Terms

Conditions

Pelvic Organ Prolapse; Cystocele; Uterine Prolapse; Pelvic Floor Disorders

Condition Hierarchy (Ancestors)

Prolapse; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Uterine Diseases; Genital Diseases, Female; Genital Diseases; Pregnancy Complications

Results Point of Contact

• Title: Dr. David D. Rahn
• Organization: University of Texas Southwestern Medical Center Dallas

david.rahn@utsouthwestern.edu

12146486430

Study Officials

• David D Rahn, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Dept. of Obstetrics & Gynecology

Study Record Dates

• First Submitted: April 23, 2015
• First Posted: May 1, 2015
• Study Start: December 1, 2016
• Primary Completion: November 29, 2021
• Study Completion: May 17, 2023
• Last Updated: September 6, 2023
• Results First Posted: December 16, 2022

Record last verified: 2023-08

Locations

US (3)