The Effect of Intra-vaginal Conjugated Estrogen Cream on Ring Pessary Use for Pelvic Organ Prolapse

The Effect of Intravaginal Conjugated Estrogen on Ring Pessary Use for Pelvic Organ Prolapse: A Multicenter Randomized, Double- Blind, Placebo Controlled, Clinical Trial

The primary purpose of this two-arm randomized clinical trial is to determine if in women desiring use of a pessary for pelvic organ prolapse (POP) and are successfully fit, if 1-year use and patient impression of improvement is superior in women using vaginal estrogen cream versus those using a vaginal placebo cream.

Study Overview

• Status: Unknown
• Conditions: Pelvic Floor Prolapse
• Intervention / Treatment: Drug: Vaginal Cream with Applicator [Dose Form]

Detailed Description

The study is a multi-center, randomized trial of women with symptomatic utero-vaginal or post-hysterectomy vaginal vault prolapse desiring non-surgical treatment with a pessary. This study will compare outcomes in women randomized to vaginal estrogen cream or vaginal placebo cream.

Women who meet the inclusion/exclusion criteria will be evaluated. A pessary (ring with support) will be fit by an experienced physician. After successful pessary fitting, they will be randomly divided into experimental active medication and control groups. The experimental group will start intravaginal estrogen cream, and the control group will start intravaginal estrogen-free cream. Then patients will be followed every 3months until 1year.

The purpose of this trial is to evaluate the effect of intravaginal estrogen use on pessary treatment for pelvic organ prolapse, including short-term and long-term use rate, patient impression of improvement, improvement in symptom-specific quality of life and complication incidence.

• Study Type: Interventional
• Enrollment (Anticipated): 420
• Phase: Phase 4

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Symptomatic POP, stage II, stage III or stage IV
2. Postmenopausal women (patients with serum FSH>40lu/L; or amenorrhea for 12 months)
3. Successfully fit with ring with support pessary
4. Ability to attend the clinical trial and follow-up
5. Patients and their families understand the study, are willing to participate for up to 1 year and can provide written informed consent
6. Willing and able to place vaginal cream

Exclusion Criteria:

1. Acute infection of internal genital tract
2. Hormone replacement therapy in recent 3 months
3. Suspected or untreated lower genital tract tumor
4. Genital fistula
5. Abnormally elevated intra-abdominal pressure (eg ascites, tumor, etc)
6. Life expectancy less than 1 year
7. Vaginal estrogen contraindications, including known or suspected estrogen dependent malignancies (endometrial carcinoma, melanoma), endometrial hyperplasia (thickness of endometrium≥5mm), thrombophlebitis or thromboembolic disease, undiagnosed irregular vaginal bleeding, known or suspected breast cancer, allergy to any component of the estrogen cream and severe liver disease, breast cancer
8. The volume of post-voiding residual is more than 250ml. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaginal estrogen cream; subjects will be treated with the prescribed vaginal medication, 1g per time, q d for the first 2 weeks and then 1g per time, twice a week.	Drug: Vaginal Cream with Applicator [Dose Form]; Patients with symptomatic POP will be assigned as outpatients. After the initial pessary fitting, the patients will be followed up in 2 weeks. If the prolapse is supported, no discomfort, and the patient decides to continue to use the pessary, the pessary fitting is successful. Patients with successful ring pessary fitting, who agree to participate and sign written consent, will be randomized into the vaginal estrogen group and the placebo group. The patients will be followed up every 3 months after wearing pessary combined with vaginal medication, until 1 year after wearing the pessary.; Other Names: pessary
Placebo Comparator: vaginal placebo cream; Subjects will be treated with the prescribed vaginal medication, 1g per time, q d for the first 2 weeks and then 1g per time, twice a week.	Drug: Vaginal Cream with Applicator [Dose Form]; Patients with symptomatic POP will be assigned as outpatients. After the initial pessary fitting, the patients will be followed up in 2 weeks. If the prolapse is supported, no discomfort, and the patient decides to continue to use the pessary, the pessary fitting is successful. Patients with successful ring pessary fitting, who agree to participate and sign written consent, will be randomized into the vaginal estrogen group and the placebo group. The patients will be followed up every 3 months after wearing pessary combined with vaginal medication, until 1 year after wearing the pessary.; Other Names: pessary

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects using the pessary and have very much or much improvement on the patient impression of improvement questionnaire at 1 year between the vaginal estrogen group and the placebo group.	Sustained wearing with satisfaction: continuous wearing is defined as the use of the pessary after successful fitting test. The continuous wearing time interval is from the start of wearing the pessary to cessation of pessary use.; PGI-I （patient global impression of improvement））is used to evaluate patient impression of improvement. PGI-I is divided into seven levels: very much better, much better, a little bit better, no change, a little bit worse, much worse and very much worse. The patient's response of" very much better" and" much better" is defined as a successful impression of improvement.	up to 1year after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. Comparison of symptom specific distress (PFDI-20) at 6 months and one year in subjects using the pessary in the vaginal estrogen group and the placebo group at 1 year.	Questionnaire survey: Relief of symptoms using validated instruments, Pelvic Floor Distress Inventory-20 。PFDI-20 scores 0-300, The higher the score is, the more serious the symptoms of PFD are, the greater the impact on the life of the patients.	up to 1year after randomization
1. Comparison of symptom specific impact (PFIQ-7) at 6 months and one year in subjects using the pessary in the vaginal estrogen group and the placebo group at 1 year.	Questionnaire survey: Relief of symptoms using validated instruments, pelvic floor impact questionnaire short form 7(PFIQ-7)。PFIQ-7 scores 0-300, the higher the severer negative influence on patient.	up to 1year after randomization
1. Comparison of sexual function (PISQ-12) at 6 months and one year in subjects using the pessary in the vaginal estrogen group and the placebo group at 1 year.	Questionnaire survey: Relief of symptoms using validated instruments, Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form(PISQ-12), PISQ-12 scores 0-48, the higher, the severer negative influence on patient.	up to 1year after randomization
Comparison of the adverse events of subjects wearing a pessary in the vaginal estrogen group and the placebo group at 1 year.	Complications will be asked and reported during each follow-up	up to 1year after randomization

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): May 24, 2020
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: May 10, 2020
• First Submitted That Met QC Criteria: May 13, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Actual): May 19, 2020
• Last Update Submitted That Met QC Criteria: May 13, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Vaginal estrogen cream
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Prolapse; Pelvic Organ Prolapse
• Other Study ID Numbers: ZS-2164

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Relying on sharing of online database
• IPD Sharing Time Frame: starting 6 months after publication
• IPD Sharing Supporting Information Type: Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No