Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen

NCT ID: NCT02431897

Last Updated: 2023-09-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 206 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2023-05-17

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.

Conditions

Pelvic Organ Prolapse; Urogenital Prolapse; Vaginal Vault Prolapse; Cystocele; Uterine Prolapse; Vaginal Prolapse; Pelvic Floor Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Estrogen Cream

Conjugated Estrogens cream

Group Type: EXPERIMENTAL

Conjugated Estrogens Cream

Intervention Type: 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.

Placebo Cream

Placebo cream

Group Type: PLACEBO_COMPARATOR

Placebo Cream

Intervention Type: DRUG

1g applied vaginally nightly for 2 weeks then 2x/week for \>5 weeks before surgery, then 2x/week for 1 year after surgery.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Premarin Vaginal Cream

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

• Minimum Eligible Age: 48 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: collaborator

Women and Infants Hospital of Rhode Island

OTHER

Sponsor Role: collaborator

Pfizer

INDUSTRY

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

David Rahn, MD

Associate Professor, Dept. of Obstetrics & Gynecology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David D Rahn, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Women & Infants Hospital of Rhode Island

Providence, Rhode Island, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 32541299 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38710269 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38061041 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37581673 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37431855 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37244454 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

STU 022015-117

Identifier Type: -

Identifier Source: org_study_id