## Protocol Section
### Identification Module
**NCT ID:** NCT05472779

**Acronym:** TAPER

**Brief Title:** Periurethral vs Intravaginal Estrogen for Prevention of Recurrent Urinary Tract Infections

**Official Title:** Periurethral vs Intravaginal Estrogen for Prevention of Recurrent Urinary Tract Infections: TAPER (Techniques of APplying Vaginal Estrogen for Prevention of Recurrent Urinary Tract Infections) Trial

#### Organization Study ID Info
**ID:** STUDY22010147
#### Organization
**Class:** OTHER
**Full Name:** University of Pittsburgh
### Status Module
#### Completion Date
**Date:** 2025-01-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-01-09

**Type:** ACTUAL

**Last Update Submit Date:** 2024-01-05

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-07-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-01-03

**Type:** ACTUAL

**Status Verified Date:** 2024-01

#### Study First Post Date
**Date:** 2022-07-25
**Type:** ACTUAL
**Study First Submit Date:** 2022-07-21
**Study First Submit QC Date:** 2022-07-21
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Stephanie Wang Zuo

#### Responsible Party

**Investigator Affiliation:** University of Pittsburgh

**Investigator Full Name:** Stephanie Wang Zuo

**Investigator Title:** UPMC Fellow

**Type:** SPONSOR_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Due to rising antibiotic resistance, there has been a focus on non-antibiotic prophylactic measures for postmenopausal patients with recurrent urinary tract infections (rUTI), one of which is the safe and efficacious option of vaginal estrogen therapy. Standard application of vaginal estrogen cream entails intravaginal application of the cream twice a week, but some providers counsel patients with rUTI to apply a small, pea-sized amount to the periurethral area. This ideally reduces the amount of vaginal estrogen used while attaining a similar effect. However, to date, there is no data to prove that the periurethral technique of application is similar or non-inferior to intravaginal application in preventing UTI.

### Conditions Module

**Conditions:**

- Recurrent Urinary Tract Infection

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** SINGLE

**Who Masked:**

- INVESTIGATOR

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 108

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Intravaginal application of 1 gram estradiol cream at bedtime twice a week for 6 months

**Intervention Names:**

- Drug: Intravaginal application of estradiol cream

**Label:** Intravaginal Estrogen Application

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** Periurethral application of 0.5 gram estradiol cream at bedtime twice a week for 6 months

**Intervention Names:**

- Drug: Periurethral application of estradiol cream

**Label:** Periurethral Estrogen Application

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Periurethral Estrogen Application

**Description:** The experimental group will apply estradiol cream in a different location (periurethral) and at a smaller dose (0.5 gram) compared to the control group.

**Name:** Periurethral application of estradiol cream

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Intravaginal Estrogen Application

**Description:** The control group will apply 1 gram estradiol cream intravaginally using an applicator.

**Name:** Intravaginal application of estradiol cream

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Percentage of participants who are UTI-free at 6 months

**Time Frame:** 6 months

#### Secondary Outcomes

**Description:** Questionnaire assessment of urinary symptoms and symptom distress (Urogenital Distress Inventory, Short Form), total score range 0-100 with higher numbers representing worse urinary symptoms

**Measure:** Change from baseline in urinary symptoms at 6 months

**Time Frame:** Baseline, 6 months

**Description:** Questionnaire assessment of vaginal symptoms and bother using 5-point Likert scale, developed by research team

**Measure:** Change from baseline in vaginal symptoms at 6 months

**Time Frame:** Baseline, 6 months

**Description:** Questionnaire assessment of sexual function (Female Sexual Function Index-6) with scores ranging from 2 to 30, with 19 and below denoting sexual dysfunction.

**Measure:** Change from baseline in sexual function at 6 months

**Time Frame:** Baseline, 6 months

**Description:** Estradiol cream tubes will be weighed at each research visit in grams

**Measure:** Amount of estrogen cream used

**Time Frame:** 6 months

**Description:** Questionnaire assessment of patient experience using 5-point Likert and open-ended questions, developed by the research team

**Measure:** Participant experience with use of estrogen cream

**Time Frame:** 6 months

**Description:** Assessment using pH strips during pelvic examination

**Measure:** Change from baseline in vaginal pH at 6 months

**Time Frame:** Baseline, 6 months

**Description:** Assessment of vaginal cell types using a superficial swab, collected from proximal vagina

**Measure:** Change from baseline in vaginal maturation index at 6 months

**Time Frame:** Baseline, 6 months

**Description:** Clean catch urine and vaginal swab sample collection with quantification of Lactobacillus

**Measure:** Change from baseline in Vaginal and urinary Lactobacillus levels at 6 months

**Time Frame:** Baseline, 6 months

**Description:** Clean catch urine and vaginal swab sample collection for quantification of E. coli

**Measure:** Change from baseline in Vaginal and urinary E. coli levels at 6 months

**Time Frame:** Baseline, 6 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Postmenopausal (definition: No menses for 1 or more years or surgical menopause (bilateral oophorectomy). If there is a past history of hysterectomy, patient must be age 56 or older (95th percentile for age at menopause) or have laboratory evidence of menopause (ie. FSH \>30))
* Meets criteria for recurrent urinary tract infections (UTIs) with 2 or more UTI in 6 months or 3 or more UTI in 1 year
* May include patients who used vaginal estrogen previously if they have stopped use for 3 or more months prior to inclusion into study.
* Patients must be recommended vaginal estrogen as part of normal clinical care for prevention of recurrent UTI

Exclusion Criteria:

* Current use of vaginal or oral estrogen products
* Inability or refusal to use vaginal estrogen
* Daily antibiotic use
* Significant vaginal stenosis (eg. due to lichen sclerosis, radiation or obliterative prolapse surgery) that would prohibit use of a vaginal applicator (ie. genital hiatus \<1cm)
* Inability to use vaginal applicator and without caregiver who can administer (eg. provider-managed pessary use, significant arthritis)
* Frequent (1x weekly or more frequent) use of bladder instillations containing an antibiotic
* Known hydronephrosis as a result of incomplete bladder emptying
* Use of intermittent or indwelling urinary catheterization
* Known bladder stones, mesh erosion into bladder, or foreign object in bladder
* Unable to consent for self
* Active treatment for an estrogen-dependent malignancy

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** zuos@upmc.edu

**Name:** Stephanie W Zuo, MD

**Phone:** 412-270-4818

**Role:** CONTACT

**Contact 2:**

**Email:** baranskil@mail.magee.edu

**Name:** Lindsey Baranski

**Phone:** 412-641-7894

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Cranberry Township

**Contacts:**

***Contact 1:***

- **Name:** Lindsey Baranski

- **Role:** CONTACT

**Country:** United States

**Facility:** UPMC Lemieux Sports Complex

**State:** Pennsylvania

**Status:** RECRUITING

**Zip:** 16066

**Location 2:**

**City:** Erie

**Contacts:**

***Contact 1:***

- **Name:** Linda Paterniti

- **Role:** CONTACT

**Country:** United States

**Facility:** UPMC Hamot

**State:** Pennsylvania

**Status:** RECRUITING

**Zip:** 16550

**Location 3:**

**City:** Pittsburgh

**Contacts:**

***Contact 1:***

- **Name:** Lindsey Baranski

- **Role:** CONTACT

**Country:** United States

**Facility:** University of Pittsburgh Medical Center-Magee Womens Hospital

**State:** Pennsylvania

**Status:** RECRUITING

**Zip:** 15213

**Location 4:**

**City:** Pittsburgh

**Contacts:**

***Contact 1:***

- **Name:** Lindsey Baranski

- **Role:** CONTACT

**Country:** United States

**Facility:** UPMC Passavant-McCandless

**State:** Pennsylvania

**Status:** RECRUITING

**Zip:** 15237

#### Overall Officials

**Official 1:**

**Affiliation:** University of Pittsburgh Medical Center

**Name:** Stephanie W Zuo, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

- ID: D000014570

- Term: Urologic Diseases

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000052801

- Term: Male Urogenital Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

### Condition Browse Module - Browse Leaves

- ID: M10283

- Name: Infections

- Relevance: HIGH

- As Found: Infection

- ID: M6368

- Name: Communicable Diseases

- Relevance: HIGH

- As Found: Infection

- ID: M17302

- Name: Urinary Tract Infections

- Relevance: HIGH

- As Found: Urinary Tract Infections

- ID: M14850

- Name: Recurrence

- Relevance: HIGH

- As Found: Recurrent

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: M17319

- Name: Urologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000007239

- Term: Infections

- ID: D000003141

- Term: Communicable Diseases

- ID: D000014552

- Term: Urinary Tract Infections

- ID: D000012008

- Term: Recurrence

### Intervention Browse Module - Ancestors

- ID: D000004967

- Term: Estrogens

- ID: D000006728

- Term: Hormones

- ID: D000006730

- Term: Hormones, Hormone Substitutes, and Hormone Antagonists

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000080066

- Term: Contraceptive Agents, Hormonal

- ID: D000003270

- Term: Contraceptive Agents

- ID: D000012102

- Term: Reproductive Control Agents

- ID: D000003271

- Term: Contraceptive Agents, Female

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Repr

- Name: Reproductive Control Agents

### Intervention Browse Module - Browse Leaves

- ID: M8116

- Name: Estrogens

- Relevance: LOW

- As Found: Unknown

- ID: M266279

- Name: Estradiol 17 beta-cypionate

- Relevance: HIGH

- As Found: Cell lymphoma

- ID: M266280

- Name: Estradiol 3-benzoate

- Relevance: HIGH

- As Found: Cell lymphoma

- ID: M8108

- Name: Estradiol

- Relevance: HIGH

- As Found: Cell lymphoma

- ID: M234941

- Name: Polyestradiol phosphate

- Relevance: HIGH

- As Found: Cell lymphoma

- ID: M9789

- Name: Hormones

- Relevance: LOW

- As Found: Unknown

- ID: M9788

- Name: Hormone Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M6494

- Name: Contraceptive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M2116

- Name: Contraceptive Agents, Hormonal

- Relevance: LOW

- As Found: Unknown

- ID: M6495

- Name: Contraceptive Agents, Female

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000007630

- Term: Estradiol 17 beta-cypionate

- ID: C000074283

- Term: Estradiol 3-benzoate

- ID: D000004958

- Term: Estradiol

- ID: C000008958

- Term: Polyestradiol phosphate

### Misc Info Module

- Version Holder: 2024-05-24
