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Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen (IMPROVE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02431897
Recruitment Status : Completed
First Posted : May 1, 2015
Results First Posted : December 16, 2022
Last Update Posted : September 6, 2023
Sponsor:
Collaborators:
University of Alabama at Birmingham
Women and Infants Hospital of Rhode Island
Pfizer
Information provided by (Responsible Party):
David Rahn, MD, University of Texas Southwestern Medical Center

Tracking Information
First Submitted Date  ICMJE April 23, 2015
First Posted Date  ICMJE May 1, 2015
Results First Submitted Date  ICMJE November 16, 2022
Results First Posted Date  ICMJE December 16, 2022
Last Update Posted Date September 6, 2023
Actual Study Start Date  ICMJE December 2016
Actual Primary Completion Date November 29, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 15, 2022)
Surgical "Failure" Defined by (i) Anatomic Assessment of Prolapse, (ii) Presence of Bulge Symptoms, and/or (Iii) Retreatment of Prolapse [ Time Frame: 12 months ]
Cumulative failures, as measured by (i) anatomic assessment of prolapse, (ii) presence of bulge symptoms, and/or (iii) retreatment of pelvic organ prolapse
Original Primary Outcome Measures  ICMJE
 (submitted: April 27, 2015)
Surgical "success" or "failure" defined by (i) anatomic assessment of prolapse, (ii) presence or absence of bulge symptoms, (iii) retreatment of prolapse [ Time Frame: 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2022)
  • Condition Specific (i.e. Pelvic Organ Prolapse) Symptom Bother as Measured by Pelvic Floor Distress Inventory-20 (PFDI-20) Questionnaire [ Time Frame: 12 months ]
    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)
  • Condition Specific (i.e. Pelvic Organ Prolapse) Quality of Life as Measured by Pelvic Floor Impact Questionnaire-7 (PFIQ-7) [ Time Frame: 12 months ]
    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)
  • Generic Quality of Life as Measured by SF-12 Questionnaire [ Time Frame: 12 months ]
    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.
  • 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 Frame: Time of surgery ]
    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.
  • 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 Frame: 12 months ]
    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.
  • Urinary Symptoms as Measured by Urinary Subscale Questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire [ Time Frame: Time of surgery ]
    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.
  • Urinary Symptoms as Measured by Urinary Subscale Questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire [ Time Frame: 12 months ]
    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.
  • Sexual Function as Measured by the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR) [ Time Frame: Time of surgery ]
    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.
  • Sexual Function as Measured by the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR) [ Time Frame: 12 months ]
    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.
  • Number of Participants With Adverse Events [ Time Frame: 12 months ]
    Number of participants reporting any adverse events from baseline randomization to 12 months postoperatively
Original Secondary Outcome Measures  ICMJE
 (submitted: April 27, 2015)
  • Condition specific (i.e. pelvic organ prolapse) quality of life as measured by Pelvic Floor Distress Inventory-20 (PFDI-20) questionnaire [ Time Frame: Baseline, 12 months ]
    Change in questionnaire scores from baseline to 12 months
  • Condition specific (i.e. pelvic organ prolapse) quality of life as measured by Pelvic Floor Impact Questionnaire-7 (PFIQ-7) [ Time Frame: Baseline, 12 months ]
    Change in questionnaire scores from baseline to 12 months
  • Generic quality of life as measured by SF-12 questionnaire [ Time Frame: Baseline, 12 months ]
    Change in questionnaire scores from baseline to 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 Frame: Baseline, time of surgery (8 wk) ]
    Change in questionnaire scores from baseline to 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 [ Time Frame: Baseline, 12 months ]
    Change in questionnaire scores from baseline to 12 months
  • Urinary symptoms as measured by urinary subscale questions of the Pelvic Floor Impact Questionnaire (PFIQ-7), i.e. the Urinary Impact Questionnaire [ Time Frame: Baseline, time of surgery (8 wk) ]
    Change in questionnaire scores from baseline to 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 [ Time Frame: Baseline, 12 months ]
    Change in questionnaire scores from baseline to 12 months
  • Overactive bladder symptoms (urinary frequency) as measured by voiding diary [ Time Frame: Baseline, time of surgery (8 wk) ]
    Change in voiding frequency from baseline to time of surgery
  • Stress urinary incontinence as measured by cough stress test [ Time Frame: Baseline, time of surgery (8 wk) ]
    Change in proportion of patients with/without positive cough stress test from baseline to time of surgery
  • Sexual function as measured by the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) [ Time Frame: Baseline, time of surgery (8 wk) ]
    Change in questionnaire scores from baseline to time of surgery
  • Sexual function as measured by the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) [ Time Frame: Baseline, 12 months ]
    Change in questionnaire scores from baseline to 12 months
  • Number of participants with adverse events [ Time Frame: through 12 months ]
    Comparison of proportions by treatment group
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen
Official Title  ICMJE Investigation to Minimize Prolapse Recurrence of the Vagina Using Estrogen
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Pelvic Organ Prolapse
  • Urogenital Prolapse
  • Vaginal Vault Prolapse
  • Cystocele
  • Uterine Prolapse
  • Vaginal Prolapse
  • Pelvic Floor Disorders
Intervention  ICMJE
  • 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.
    Other Name: Premarin Vaginal Cream
  • 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.
Study Arms  ICMJE
  • Experimental: Estrogen Cream
    Conjugated Estrogens cream
    Intervention: Drug: Conjugated Estrogens Cream
  • Placebo Comparator: Placebo Cream
    Placebo cream
    Intervention: Drug: Placebo Cream
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 9, 2020)
206
Original Estimated Enrollment  ICMJE
 (submitted: April 27, 2015)
276
Actual Study Completion Date  ICMJE May 17, 2023
Actual Primary Completion Date November 29, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 48 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02431897
Other Study ID Numbers  ICMJE STU 022015-117
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party David Rahn, MD, University of Texas Southwestern Medical Center
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Texas Southwestern Medical Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • University of Alabama at Birmingham
  • Women and Infants Hospital of Rhode Island
  • Pfizer
Investigators  ICMJE
Principal Investigator: David D Rahn, MD University of Texas Southwestern Medical Center
PRS Account University of Texas Southwestern Medical Center
Verification Date August 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP