Biological Mesh Closure of the Pelvic Floor After Extralevator Abdomino Perineal Resection for Rectal Cancer

NCT ID: NCT01927497

Last Updated: 2021-08-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-08
• Study Completion Date: 2015-09-01

Brief Summary

Rationale: Approximately 800 abdominoperineal resections (APR) are performed for rectal cancer each year in the Netherlands. The extralevator approach (eAPR) reduces the rate of positive margins and improves oncological outcome in distal rectal cancer. However, wider excisions increase wound healing problems and development of perineal hernia. This has resulted in a progressive increase of the use of musculocutaneous flaps and biological meshes associated with a substantial increase of costs, which is not supported by proper data.

Objective: The aim of this study is to determine the cost-effectiveness of pelvic floor reconstruction using a biological mesh after standardized eAPR with neo-adjuvant (chemo)radiotherapy.

Study design: This is a multicenter study in which patients undergoing an eAPR are randomized between standard care using primary closure of the perineum and the experimental arm with assisted closure using a biological mesh.

Study population: Patients with a clinical diagnosis of primary rectal cancer who are scheduled for eAPR after neo-adjuvant (chemo)radiotherapy. A total number of 104 patients will be randomized.

Intervention: The intervention in the experimental arm consists of suturing a biological mesh derived from porcine dermis in the pelvic floor defect, followed by perineal closure similar to the control arm.

Main study parameters/endpoints: The primary endpoint is the percentage of uncomplicated perineal wound healing (Souphampton wound score less than II at day 30). Secondary endpoints are hospital stay, incidence of perineal hernia, quality of life, and costs.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Both primary perineal closure and biological mesh assisted closure are being performed in daily clinical practise. The potential benefit resulting from participation of the study in patients randomized for biological mesh assisted closure may be a higher chance of uncomplicated perineal wound healing and lower perineal hernia rate. On the other hand, the use of a biological mesh has been associated with increased postoperative pain and seroma formation.

Conditions

Rectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Biological mesh closure

Biological mesh reconstruction of the pelvic floor after extralevator abdomino perineal resection

Group Type: EXPERIMENTAL

Biological mesh assisted perineal closure

Intervention Type: PROCEDURE

The eAPR procedure will be performed in an identical way as described for the control arm of the study, and this is preferably followed by an omental plasty. The intervention in the experimental arm consists of suturing an acellular biological mesh derived from porcine dermis in the pelvic floor defect (Strattice™, 6x10 cm). The mesh will be sutured at each side of the coccyx or distal sacrum with Prolene or PDS to the discretion of the surgeon. Laterally, the mesh is attached to the remainings of the levator complex and, anteriorly, to the transverse perineal muscle or posterior vaginal wall. A suction drain will be inserted and positioned on top of the mesh. The perineal subcutaneous fat and skin will be subsequently closed in layers similar to primary simple closure as performed in the standard arm.

Primary perineal closure

Primary perineal closure after extralevator abdomino perineal resection

Group Type: ACTIVE_COMPARATOR

Primary perineal closure

Intervention Type: PROCEDURE

The perineal phase of the APR will be performed according to the principles of an extralevator APR, which means that the levator muscles will be laterally transected in order to leave a muscular cuff around the tumour. The coccyx will not be routinely resected, but only if indicated based on surgical exposure or oncological principles. The extent of excision of perineal skin and ischioanal fat will be as limited as oncologically justified. Preferably, an omental plasty is positioned in the pelvic cavity following resection. Closure of the perineum in the control arm consists of stitching the perineal subcutaneous fat together using interrupted Vicryl sutures in one or two layers. Subsequently, the skin will be closed using interrupted sutures according to the preference of the surgeon. Placement of a transabdominal or transperineal drain will be at the discretion of the surgeon.

Interventions

Biological mesh assisted perineal closure

The eAPR procedure will be performed in an identical way as described for the control arm of the study, and this is preferably followed by an omental plasty. The intervention in the experimental arm consists of suturing an acellular biological mesh derived from porcine dermis in the pelvic floor defect (Strattice™, 6x10 cm). The mesh will be sutured at each side of the coccyx or distal sacrum with Prolene or PDS to the discretion of the surgeon. Laterally, the mesh is attached to the remainings of the levator complex and, anteriorly, to the transverse perineal muscle or posterior vaginal wall. A suction drain will be inserted and positioned on top of the mesh. The perineal subcutaneous fat and skin will be subsequently closed in layers similar to primary simple closure as performed in the standard arm.

Intervention Type: PROCEDURE

Primary perineal closure

The perineal phase of the APR will be performed according to the principles of an extralevator APR, which means that the levator muscles will be laterally transected in order to leave a muscular cuff around the tumour. The coccyx will not be routinely resected, but only if indicated based on surgical exposure or oncological principles. The extent of excision of perineal skin and ischioanal fat will be as limited as oncologically justified. Preferably, an omental plasty is positioned in the pelvic cavity following resection. Closure of the perineum in the control arm consists of stitching the perineal subcutaneous fat together using interrupted Vicryl sutures in one or two layers. Subsequently, the skin will be closed using interrupted sutures according to the preference of the surgeon. Placement of a transabdominal or transperineal drain will be at the discretion of the surgeon.

Intervention Type: PROCEDURE

Other Intervention Names

Biological Mesh; Strattice™; Strattice® Reconstructive Tissue Matrix; Lifecell; Porcine dermal Mesh; Primary closure; Perineal wound closure

Eligibility Criteria

Inclusion Criteria

1. Age of 18 years or higher.

2. Planned for eAPR for primary rectal cancer.

3. Life expectancy of more than 2 years.

4. Ability to return for all scheduled and required study visits.

5. Preoperative (chemo)radiotherapy.

6. Written informed consent for study participation.

Exclusion Criteria

1. Previous pelvic irradiation for other cancers (i.e. prostate cancer).

2. Total exenteration or sacral resection above level S4/S5.

3. Sensitivity to porcine derived products or polysorbate.

4. Severe systemic diseases affecting wound healing (i.e. renal failure requiring dialysis, liver cirrhosis, and immune compromised status like HIV).

5. Collagen disorders (i.e. Marfan).

6. Enrolment in trials with overlapping primary endpoint or otherwise expected influence on wound healing (i.e. biological therapy like antiangiogenic agents).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

LifeCell

INDUSTRY

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: lead

Responsible Party

P.J. Tanis

dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gijsbert D. Musters, M.D.

Role: STUDY_CHAIR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Willem A. Bemelman, Prof, PhD, M.D.

Role: PRINCIPAL_INVESTIGATOR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Harm J. Rutten, M.D. PhD

Role: PRINCIPAL_INVESTIGATOR

Catharina Ziekenhuis Eindhoven

Baljit Singh, M.D. PhD

Role: PRINCIPAL_INVESTIGATOR

Leicester hospital, Leicester

Marcel G.W. Dijkgraaf, M.D.

Role: PRINCIPAL_INVESTIGATOR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Locations

Academic Medical Cener

Amsterdam, North Holland, Netherlands

Countries

Netherlands

References

Musters GD, Bemelman WA, Bosker RJ, Burger JW, van Duijvendijk P, van Etten B, van Geloven AA, de Graaf EJ, Hoff C, de Korte N, Leijtens JW, Rutten HJ, Singh B, van de Ven A, Vuylsteke RJ, de Wilt JH, Dijkgraaf MG, Tanis PJ. Randomized controlled multicentre study comparing biological mesh closure of the pelvic floor with primary perineal wound closure after extralevator abdominoperineal resection for rectal cancer (BIOPEX-study). BMC Surg. 2014 Aug 27;14:58. doi: 10.1186/1471-2482-14-58.

Reference Type: DERIVED

PMID: 25163547 (View on PubMed)

Other Identifiers

NTR3717

Identifier Type: OTHER

Identifier Source: secondary_id

METC 2012_360

Identifier Type: -

Identifier Source: org_study_id