PACT: Permanent Versus Absorbable Colpopexy Trial

• Sponsor: University of North Carolina, Chapel Hill (Other)
• Overall Status: Completed
• CT.gov ID: NCT02277925
• Collaborator: Northwestern University (Other), Augusta University (Other), Wake Forest University Health Sciences (Other)
• Enrollment: 204
• Locations: 5
• Arms: 2
• Actual Duration (Months): 54
• Patients Per Site: 40.8
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

Primary Aim:

The primary aim of this randomized controlled trial (RCT) is to compare vaginal mesh and suture exposure rates in women undergoing robotic total hysterectomy and sacrocolpopexy with a light-weight polypropylene mesh (Upsylon™ y-mesh) using permanent (polytetrafluoroethylene, Gore-Tex) versus delayed absorbable monofilament (2-0 polydioxanone, PDS) sutures through 1-year.

Secondary Aims:

1. To compare the 1-year composite success rate (leading edge of prolapse is at or above the hymen and apex has descended less than 1/3 of the vaginal length, no subjective feeling of bulge; and no retreatment for pelvic organ prolapse (POP) or vaginal mesh exposure) of permanent versus delayed absorbable sutures for mesh graft attachment during robotic total hysterectomy and sacrocolpopexy.

2. To evaluate adverse outcomes in each group

Condition or Disease	Intervention/Treatment	Phase
Pelvic Organ Prolapse	Other: Polytetrafluoroethylene; Other: Polydioxanone	N/A

Detailed Description

Symptomatic pelvic organ prolapse is common and 13%1 to 19%2,3 of women undergo surgical repair. Reconstructive pelvic surgery is broadly divided into procedures that rely on existing native tissue versus the use of graft augmentation, either with synthetic or biologic materials. Native tissue vaginal repair, while associated with the lowest rate of surgical complications,4 has a high rate of recurrent prolapse. A recent randomized trial of uterosacral versus sacrospinous ligament fixation for POP demonstrated a 30% recurrence rate at 2 years.3

Abdominal sacrocolpopexy (SCP) is considered to be the most durable operation for advanced pelvic organ prolapse with reoperation rates of less than 5%.5-7 Minimally-invasive techniques of SCP, such as robotic-assistance, are associated with improved recovery times and less cost than abdominal SCP without a demonstrable difference in efficacy.8,9 While traditionally reserved for women with vaginal vault prolapse, SCP is increasingly considered as a primary surgical option for women who present with uterovaginal prolapse in an attempt to improve longer-term surgical outcomes. The optimal management of the uterus and cervix in these cases is unclear.

Rationale for total versus supracervical hysterectomy with concomitant SCP

While supracervical hysterectomy and concomitant SCP are associated with lower rates of mesh exposure,10-12 potential negative consequences of a supracervical hysterectomy include morcellation of unanticipated uterine malignancy,13 cervical stump prolapse/elongation, cyclic vaginal bleeding, and reduced anterior vaginal support (Myers EM, Matthews et al., in press). When conducting a supracervical hysterectomy, power morcellators are the most common method used to extract the amputated uterine corpus. The potential risks of power morcellation were recently highlighted by the FDA safety notification which focused on the potential to disseminate fragments of an undiagnosed uterine leiomyosarcoma throughout the abdomen, which negatively impacts prognosis (http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm393576.htm). With these recent developments the focus has shifted towards performing total hysterectomy for delivery of an intact specimen through the vagina.

Vaginal mesh exposure has been a problematic complication with both abdominal SCP and minimally invasive SCP. Widely disparate rates of mesh exposure ranging from 0%14 to 27%15 have been reported. A systematic review of ASCP outcomes in 2004 reported an overall rate of 3.4%,6 and a recent meta-analysis of robotic-assisted SCP reported an overall rate of 2%.16 Some consistent risk factors for mesh exposure are non-Type 1 polypropylene mesh (knitted, small-pore mesh materials) and smoking.17,18 Some studies have identified total hysterectomy as a significant risk factor. In an evaluation of patients enrolled in the CARE trial, 6% had evidence of mesh exposure at 2 years, with concomitant hysterectomy presenting almost a 5-fold increased risk.18 The rate at 6 years rose to 10.5%. 5 More than 50% of subjects in this trial, however, had a non-Type 1 polypropylene mesh. Akyol et al. demonstrated a 2-fold increased risk (12%)19 and Bensinger et al. a 7-fold increased risk (8.2%)20 of concomitant total hysterectomy. In contrast, 4 retrospective studies in which Type1 polypropylene mesh was used revealed no increased risk of mesh erosion with concomitant total hysterectomy.14,21-23 These widely discrepant rates of mesh exposure may be related to surgical technique, graft material and/or suture materials used for mesh attachment.

Rationale for need to study suture material for mesh attachment during SCP

The effect of suture on mesh exposure may be as significant as concomitant hysterectomy or mesh type. At UNC, we reported on mesh exposure using a permanent suture for mesh attachment during SCP with and without concomitant total hysterectomy, with rates of 8% at 1 year.24 There is some evidence that a delayed absorbable suture may reduce the risk of mesh or suture erosion. In a retrospective review comparing braided permanent suture to delayed absorbable monofilament suture for SCP mesh attachment, rates of mesh exposure were reduced in the absorbable suture group (3.7% vs 0%), with no associated POP recurrence.25 Similarly, in another retrospective review, when delayed absorbable monofilament suture was used for SCP mesh attachment in 67 women undergoing total abdominal hysterectomy and SCP, no mesh exposures were noted at a median follow up of 27 months.26 The use of permanent sutures for vaginal mesh attachment has historically been advocated as a means to reduce POP recurrence risk; yet, no prospective study has definitively answered this question. The tradeoff of using a permanent suture may be an increased risk of mesh or suture exposure, as a permanent suture that has breached the vaginal epithelium may serve as a nidus for bacterial seeding, theoretically increasing the risk of mesh exposure. As SCP appears to be a more durable procedure for women with advanced uterovaginal prolapse, there is an urgent need to identify the ideal method of vaginal mesh attachment that minimizes the risk of mesh-related complications while maintaining effectiveness of the POP repair.

Choice of mesh material

Upsylon™ (Boston Scientific, Natick, MA) is a pre-formed Y-mesh that is light-weight (25 g/m2), composed of Type I polypropylene material, with a pore size of 2.8 mm2 and surface area ration of 1.11. It was FDA approved in 2012. The mesh is blue in color that may aide in the ability to detect even small areas of mesh exposure and erosion. No data currently exist regarding the performance of this particular mesh product in SCP. It is lighter in mesh weight than the IntePro™ y-mesh (American Medical Systems, Minneapolis, MN), which we previously used in the comparative trial of robotic to abdominal SCP in which our mesh exposure rates were 8%.

The primary aim of this randomized trial, therefore, is to test the hypothesis that use of the Upsylon™ mesh with a delayed absorbable suture for mesh attachment at the time of robotic-assisted total laparoscopic hysterectomy and SCP will reduce the risk of vaginal mesh and/or suture exposure compared to a permanent monofilament suture. Secondary aims will include an evaluation of the effect of this light-weight mesh and absorbable suture on prolapse and quality of life outcomes and surgical complications at 1 year after surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 204 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Permanent Versus Delayed-absorbable Monofilament Suture for Vaginal Graft Attachment During Minimally-invasive Total Hysterectomy and Sacrocolpopexy: A Randomized Clinical Trial
• Actual Study Start Date: Apr 7, 2015
• Actual Primary Completion Date: Oct 7, 2019
• Actual Study Completion Date: Oct 7, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Gore-Tex permanent suture Participants in this arm will receive Gore-Tex permanent suture	Other: Polytetrafluoroethylene; Suture used to attach mesh during sacral colpopexy surgery; Other Names: Gore-Tex permanent suture
Experimental: PDS delayed absorbable suture Participants in this arm will receive 2-0 PDS delayed absorbable suture	Other: Polydioxanone; Suture used to attach mesh during sacral colpopexy surgery; Other Names: 2-0 PDS delayed absorbable monofilament suture

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Vaginal Mesh or Suture Exposure [1 year]

   Total number of participants with vaginal mesh and/or suture exposure thru 1 year

Secondary Outcome Measures

1. Number of Participants With Treatment Success [1 year]

   Total number of participants with treatment success, which was a composite measure of 1) leading edge of prolapse not beyond hymen and apex not descended > 1/3 of vaginal length, 2) no subjective feeling of bulge on validated questionnaire, and 3) no prolapse re-treatment with pessary or surgery

2. Pelvic Floor Distress Inventory-20 (PFDI-20) Mean Score [1 year]

   Condition-specific questionnaire, pelvic floor distress inventory-20 (PFDI-20) is used. Minimum value is 0. Maximum is 300. Higher scores mean more bothersome symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥18

• Subject must have apical with anterior or posterior vaginal prolapse with leading edge of prolapse to or beyond the hymen. This is defined as stage 2-4 pelvic organ prolapse ( C > - (TVL / 2) AND Ba or Bp ≥ 0 by the POP)

• Subject reports a bothersome bulge they can see or feel per PFDI-20, question 3, response of 2 or higher (i.e., responses of "somewhat", "moderately", or "quite a bit")

• Eligible for robotic or laparoscopic sacral colpopexy

• Desires surgical treatment for primary, symptomatic uterovaginal prolapse

• English speaking

• Willing to undergo hysterectomy

Exclusion Criteria:

• Patients who had prior hysterectomy

• Patients who are not surgical candidates due to medical comorbidities

• Current foreign body complications (including but not limited to erosion, fistula, abscess). This covers foreign bodies of any type (e.g. synthetic and biologic including allograft, xenograft).

• Desires uterine conservation

• Inability to give informed consent or to complete the testing or data collection

• Anticipated circumstances resulting in an inability to follow up (geographic relocation, etc).

• Pregnant or intends to become pregnant

• Active/chronic systemic infection including any gynecologic infection, untreated UTI or tissue necrosis

• History of pelvic organ cancer (e.g. uterine, ovarian, bladder, or cervical)

• Prior or currently undergoing radiation, laser therapy, or chemotherapy in the pelvic area

• Subject has taken systemic steroids (within the last month), or immunosuppressive or immunomodulatory treatment (within the last 3 months)

• Systemic connective tissue disease (e.g. scleroderma, Marfan's syndrome, Ehlers Danhlos, collagenosis, polymyositis or polymyalgia rheumatica)

• Chronic systemic pain that includes the pelvic area or chronic focal pain that involves the pelvis

• Poorly controlled diabetes mellitus (DM), as indicated by Hemoglobin A1c > 9

• Those requiring concomitant rectopexy

• Subject is not able to conform to steep trendelenburg position

• Known sensitivity to polypropylene

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Augusta University Medical Center	Augusta	Georgia	United States	30912
2	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
3	UNC Chapel Hill	Chapel Hill	North Carolina	United States	27516
4	Carolinas HealthCare System	Charlotte	North Carolina	United States	28207
5	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27595

Sponsors and Collaborators

• University of North Carolina, Chapel Hill
• Northwestern University
• Augusta University
• Wake Forest University Health Sciences

Investigators

• Principal Investigator: Elizabeth Geller, MD, University of North Carolina, Chapel Hill

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 18, 2016

More Information

Publications

None provided.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT02277925
• Other Study ID Numbers: 14-2402
• First Posted: Oct 29, 2014
• Last Update Posted: Nov 19, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by University of North Carolina, Chapel Hill: Pelvic Organ Prolapse; Vaginal mesh exposure rates; Vaginal suture exposure rates
• Additional relevant MeSH terms: Prolapse; Pelvic Organ Prolapse

Study Results

Participant Flow

Arm/Group Title	Gore-Tex Permanent Suture	PDS Delayed Absorbable Suture
Arm/Group Description	Participants in this arm will receive Gore-Tex permanent suture	Participants in this arm will receive 2-0 PDS delayed absorbable suture
Period Title: Overall Study
STARTED	102	102
Surgery	99	101
COMPLETED	95	87
NOT COMPLETED	7	15

Baseline Characteristics

Arm/Group Title	Gore-Tex Permanent Suture	PDS Delayed Absorbable Suture	Total
Arm/Group Description	Participants in this arm will receive Gore-Tex permanent suture	Participants in this arm will receive 2-0 PDS delayed absorbable suture	Total of all reporting groups
Overall Participants	99	101	200
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.7 (10.7)	59.0 (10.2)	59.3 (10.4)
Sex: Female, Male (Count of Participants)
Female	99 100%	101 100%	200 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	14 14.1%	11 10.9%	25 12.5%
Not Hispanic or Latino	85 85.9%	90 89.1%	175 87.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1%	1 0.5%
Asian	1 1%	2 2%	3 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 7.1%	8 7.9%	15 7.5%
White	90 90.9%	89 88.1%	179 89.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1%	1 1%	2 1%
Region of Enrollment (Count of Participants)
United States	99 100%	101 100%	200 100%
Current smoker (Count of Participants)
Count of Participants [Participants]	2 2%	3 3%	5 2.5%
Body mass index (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.5 (5.0)	57.5 (4.7)	27.5 (4.9)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Vaginal Mesh or Suture Exposure
Description	Total number of participants with vaginal mesh and/or suture exposure thru 1 year
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Participants who underwent sacral colpopexy surgery with 1-year follow up data

Arm/Group Title	Gore-Tex Permanent Suture	PDS Delayed Absorbable Suture
Arm/Group Description	Participants in this arm will receive Gore-Tex permanent suture	Participants in this arm will receive 2-0 PDS delayed absorbable suture
Measure Participants	95	87
Count of Participants [Participants]	5 5.1%	8 7.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gore-Tex Permanent Suture, PDS Delayed Absorbable Suture
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.74
	Confidence Interval	(2-Sided) 95%; 0.59 to 5.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With Treatment Success
Description	Total number of participants with treatment success, which was a composite measure of 1) leading edge of prolapse not beyond hymen and apex not descended > 1/3 of vaginal length, 2) no subjective feeling of bulge on validated questionnaire, and 3) no prolapse re-treatment with pessary or surgery
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Participants who underwent sacral colpopexy surgery with 1-year follow-up

Arm/Group Title	Gore-Tex Permanent Suture	PDS Delayed Absorbable Suture
Arm/Group Description	Participants in this arm will receive Gore-Tex permanent suture	Participants in this arm will receive 2-0 PDS delayed absorbable suture
Measure Participants	95	87
Count of Participants [Participants]	88 88.9%	83 82.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gore-Tex Permanent Suture, PDS Delayed Absorbable Suture
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.96 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Pelvic Floor Distress Inventory-20 (PFDI-20) Mean Score
Description	Condition-specific questionnaire, pelvic floor distress inventory-20 (PFDI-20) is used. Minimum value is 0. Maximum is 300. Higher scores mean more bothersome symptoms.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gore-Tex Permanent Suture	PDS Delayed Absorbable Suture
Arm/Group Description	Participants in this arm will receive Gore-Tex permanent suture Polytetrafluoroethylene: Suture used to attach mesh during sacral colpopexy surgery	Participants in this arm will receive 2-0 PDS delayed absorbable suture Polydioxanone: Suture used to attach mesh during sacral colpopexy surgery
Measure Participants	95	87
Mean (Standard Deviation) [score on a scale]	42.4 (35.9)	37.9 (33.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gore-Tex Permanent Suture, PDS Delayed Absorbable Suture
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.39
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.5
	Confidence Interval	(2-Sided) 95%; -14.7 to 5.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events were collected from surgery to 1 year follow-up visit, approximate total of 14 months
Adverse Event Reporting Description	Systematic assessment was performed with medical records review and detailed adverse event case report forms that were completed at study visits.
Arm/Group Title	Gore-Tex Permanent Suture		PDS Delayed Absorbable Suture
Arm/Group Description	Participants in this arm will receive Gore-Tex permanent suture		Participants in this arm will receive 2-0 PDS delayed absorbable suture
All Cause Mortality
	Gore-Tex Permanent Suture		PDS Delayed Absorbable Suture
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/99 (0%)		0/101 (0%)
Serious Adverse Events
	Gore-Tex Permanent Suture		PDS Delayed Absorbable Suture
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/99 (1%)		5/101 (5%)
Blood and lymphatic system disorders
Pulmonary embolism	0/99 (0%)	0	1/101 (1%)	1
Gastrointestinal disorders
Bowel obstruction	1/99 (1%)	1	0/101 (0%)	0
Infections and infestations
Sepsis	0/99 (0%)	0	1/101 (1%)	1
Infected hematoma	0/99 (0%)	0	1/101 (1%)	1
Surgical and medical procedures
Ureteral injury	0/99 (0%)	0	1/101 (1%)	1
Port site hernia	0/99 (0%)	0	1/101 (1%)	1
Other (Not Including Serious) Adverse Events
	Gore-Tex Permanent Suture		PDS Delayed Absorbable Suture
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/99 (10.1%)		5/101 (5%)
Surgical and medical procedures
Intraoperative complications	10/99 (10.1%)	10	5/101 (5%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.