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| Name | Class |
|---|---|
| University of Alabama at Birmingham | OTHER |
| Women and Infants Hospital of Rhode Island | OTHER |
| Pfizer | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Estrogen Cream | Experimental | Conjugated Estrogens cream |
|
| Placebo Cream | Placebo Comparator | Placebo cream |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David D Rahn, MD | University of Texas Southwestern Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35249 | United States | ||
| Women & Infants Hospital of Rhode Island |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32541299 | Background | 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. | |
| 38710269 |
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Of the 206 participants consented/enrolled, 7 were not randomized: 4 withdrew consent before randomization, and 3 were found to be ineligible and were not randomized. This left n=199 for randomization.
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| ID | Title | Description |
|---|---|---|
| FG000 | Estrogen Cream | 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. |
| FG001 | Placebo Cream |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 24, 2019 |
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| 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. |
|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Number of Participants With Adverse Events | Number of participants reporting any adverse events from baseline randomization to 12 months postoperatively | 12 months |
| Providence |
| Rhode Island |
| 02905 |
| United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| Derived |
| 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. |
| 38061041 | 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. |
| 37581673 | 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. |
| 37431855 | 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. |
| 37244454 | 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. |
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.
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Estrogen Cream | 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. |
| BG001 | Placebo Cream | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Gravidity | Median | Inter-Quartile Range | pregnancies |
| |||||||||||||||
| Vaginal deliveries | Median | Inter-Quartile Range | births |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Count of Participants | Participants | 12 months |
|
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| ||||||||||||||||||||||||||||||
| 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) | Posted | Mean | Standard Error | score on a scale | 12 months |
|
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| 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) | Posted | Mean | Standard Error | score on a scale | 12 months |
|
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| 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. | Posted | Mean | Standard Error | score on a scale | 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. | Posted | Mean | Standard Error | score on a scale | 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. | Posted | Mean | Standard Error | score on a scale | 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. | Posted | Mean | Standard Error | score on a scale | Time of surgery |
|
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| 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. | Posted | Mean | Standard Error | score on a scale | 12 months |
|
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| 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. | Posted | Mean | Standard Error | score on a scale | Time of surgery |
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| 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. | Posted | Mean | Standard Error | score on a scale | 12 months |
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| Secondary | Number of Participants With Adverse Events | Number of participants reporting any adverse events from baseline randomization to 12 months postoperatively | Posted | Count of Participants | Participants | 12 months |
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From baseline randomization to 12 months postoperatively
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Estrogen Cream | 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. | 0 | 102 | 10 | 102 | 56 | 102 |
| EG001 | Placebo Cream | 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. | 0 | 97 | 11 | 97 | 51 | 97 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Trimalleolar fracture, closed | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Stroke | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Anaphylactic shock due to adverse food reaction | Immune system disorders | MedDRA 10.0 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
| |
| Fractured hip | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Infection MRSA | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
| |
| Carcinoma breast stage II | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
| |
| Endometrial carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.0 | Systematic Assessment |
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| Chest pain | Cardiac disorders | MedDRA 10.0 | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA 10.0 | Systematic Assessment |
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| Viral infection NOS | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
| |
| Volvulus | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
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| Bladder injury | Surgical and medical procedures | MedDRA 10.0 | Systematic Assessment |
| |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
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| Cardiac catheter ablation | Cardiac disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Stress urinary incontinence | Renal and urinary disorders | MedDRA 10.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Urinary tract infection | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
| |
| Yeast infection | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
| |
| Nausea and vomiting | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
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| Dyspareunia | Reproductive system and breast disorders | MedDRA 10.0 | Systematic Assessment |
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| Granulation tissue | Injury, poisoning and procedural complications | MedDRA 10.0 | Systematic Assessment |
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| Vaginal itching | Reproductive system and breast disorders | MedDRA 10.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. David D. Rahn | University of Texas Southwestern Medical Center Dallas | 12146486430 | david.rahn@utsouthwestern.edu |
| Nov 17, 2022 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 24, 2019 | Nov 17, 2022 | ICF_001.pdf |
| ID | Term |
|---|---|
| D056887 | Pelvic Organ Prolapse |
| D052858 | Cystocele |
| D014596 | Uterine Prolapse |
| D059952 | Pelvic Floor Disorders |
| ID | Term |
|---|---|
| D011391 | Prolapse |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D000091662 | Genital Diseases |
| D011248 | Pregnancy Complications |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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