Collagen Implant (Biological Mesh) Versus GM Flap for Reconstruction of Pelvic Floor After ELAPE in Rectal Cancer (NEAPE)

Nordic Extended Abdominoperineal Excision (NEAPE) Study, a RCT Comparing a Porcine Acellular Dermal Collagen Implant (Biological Mesh) With a Gluteus Maximus Flap for Reconstruction of Pelvic Floor After ELAPE in Rectal Cancer

The trial compares two different techniques for reconstruction of the lesser pelvic floor after an extended abdominoperineal excision for locally advanced rectal cancer. The alternative reconstruction techniques in the trial are:

• a technique using a gluteus maximus myocutaneous flap or
• a technique using an acellular porcine collagen implant (biological mesh)

The primary endpoint will be physical performance six months from operation and our hypothesis is that the technique using an acellular porcine implant will cause less impaired physical performance compared to the technique using a myocutaneous flap.

The study is interventional, randomized and by definition a comparative effectiveness research project.

Study Overview

• Status: Active, not recruiting
• Conditions: Rectal Cancer; Defect of Floor of Lesser Pelvis
• Intervention / Treatment: Procedure: Reconstruction with an acellular porcine dermal collagen implant (biological mesh); Procedure: Reconstruction with a gluteus maximus myocutaneous flap

Detailed Description

Extended abdominoperineal excision (EAPE) of the rectum is the potentially curative operation for rectal carcinomas too low for primary anastomosis, especially if the levator and sphincter musculature is infiltrated. This enlarged operation, when the levator musculature is excised en bloc with the rectum, creates a large defect. Primary closure is often not possible, and reconstruction with prosthetic material or a myocutaneous flap is necessary to avoid a perineal hernia. Implantation of a collagen sheet (biological mesh) has shown preliminary good results and on the other hand, the use of a gluteus myocutaneous flap is routine in many clinics. There is a lack of scientific evidence to prove which method is better for the reconstruction of the lesser pelvic floor.

The current study aims to compare the two reconstruction techniques.

Centres that treat locally advanced rectal cancers with the extended abdominoperineal excision of rectum (EAPE)[Holm et al 2007] can participate provided that:

1. the operative technique is standardized according to the study protocol
2. the centre/unit has resources for examinations of participants by a physiotherapist or a nurse
3. the centre/unit has one investigator in charge of the study locally
4. the centre/unit has an operative volume that enables at least 6 patients to be included/randomised during the anticipated three year study phase for inclusions

Centres that do not operate the rectal cancers included in this study can participate by arranging the preoperative examination and physical tests as well as follow-up of patients that are referred to other centres for the operation. In these cases the operating centre cares for the randomisation, operation and start of postoperative rehabilitation while the study follow-up and final rehabilitation can be completed at the patients' primary referral hospital. The primary referral hospital needs a site investigator in charge of study patients just like centres that do the operations.

Patients with primary or recurrent cancers of rectal origin can be included but individual patients can be included only once. Concomitant therapies are allowed and preoperative or postoperative radiation therapy and/or chemotherapy may be given or not according to local multidisciplinary team (MDT) decisions.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marja-Liisa Lammi-Tavelin, B.Sc.; Phone Number: +46-70-2012764; Email: marjaliisa.lammitavelin@vll.se
• Study Contact Backup: Name: Markku M Haapamäki, MD, PhD; Phone Number: +46-90-7851221; Email: markku.haapamaki@surgery.umu.se

Study Locations

• Finland
  • Oulu, Finland
    • Oulu University Hospital
• Sweden
  • Luleå, Sweden, 971 80
    • Sunderby County Hospital
  • Malmö, Sweden, 20502
    • Skåne Universtiy Hospital
  • Stockholm, Sweden, 171 76
    • Karolinska University Hospital, Solna
  • Umeå, Sweden, 901 85
    • Umeå University Hospital, Department of Surgical and Perioperative Sciences
  • Uppsala, Sweden, 751 85
    • Uppsala University Hospital
  • Västerås, Sweden, 72189
    • Västmanlands sjukhus Västerås
  • Östersund, Sweden, 831 83
    • Östersund hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult (18 years or older) rectal cancer patients where wide resection of pelvic floor muscles together with rectum and anal canal have made reconstruction of pelvic floor necessary i.e. primary suture of pelvic floor in the midline is not possible. Resection of coccyx is optional.

Exclusion Criteria:

• Age less than 18 years
• Very large resections including partial resection of sacrum and patients considered for bilateral flap reconstruction
• Large concomitant resection of vaginal wall where total (vaginal) wound closure is not an option
• Expected survival less than one year at operation
• Patient do not sign informed consent document

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Porcine collagen implant (biological mesh); Reconstruction with an acellular porcine dermal collagen implant (biological mesh).	Procedure: Reconstruction with an acellular porcine dermal collagen implant (biological mesh); Reconstruction of floor of lesser pelvis with an acellular porcine dermal collagen implant (biological mesh) after extended excision of rectum including levator muscles in advanced low rectal cancer.
Active Comparator: Gluteus maximus flap; Reconstruction with a gluteus maximus myocutaneous flap.	Procedure: Reconstruction with a gluteus maximus myocutaneous flap; Reconstruction of floor of lesser pelvis with an gluteus maximus myocutaneous flap after extended excision of rectum including levator muscles in advanced low rectal cancer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance in Timed-Stands Test	Timed-Stands test is a combined measure of physical performance depending on at least muscle strength, balance, tenderness of gluteal skin and muscles and co-ordination of motion.	6 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in physical performance	Change in Timed-Stands Test performance	3, 6 and 12 months after surgery compared with preoperative results
Primary wound healing assessed with the Southampton Wound Assessment Scale	The Southampton Wound Assessment Scale is a validated measure of wound healing after surgery.	3 months from operation
Complications according to classification by Dindo-Clavien	The Dindo-Clavien classification of surgical complications is a validated instrument.	3, 6 and 12 months after surgery
Proportion of persistent perineal sinus or fistula	Proportion of patients with the wound healing defect of all patients in the particular study arm	3, 6 and 12 months after surgery
Ability to sit	Ability to sit is graded with a scale in three degrees.	3, 6 and 12 months after surgery
Change of pain and discomfort in gluteal region measured with VAS	A standard visual analogue scale (VAS) from 0-100 mm is used.	3, 6 and 12 months after surgery compared to preoperative
Pain and discomfort in gluteal region, spot measures with VAS	A standard visual analogue scale (VAS) from 0-100 mm is used.	3, 6 and 12 months after surgery
Change of quality of life measured with EQ-5D and EORTC forms C30 and CR29	EQ-5D and EORTC are validated quality of life instruments	3, 6 and 12 months after surgery compared to preoperative
Quality of life spot measures	Quality of life at specified time points	3, 6 and 12 months after surgery
Length of hospital stay	Length of index hospital stay in days.	Six months after surgery
Costs of surgical treatment	Hospital expenses converted to US$	12 months after surgery
Quality-adjusted life years (QALYs gained)	Quality adjusted life year (QALY) is calculated using an quality of life utility index at repeated time points. The utility index is adjusted for the relevant background population.	12 months after surgery
Local recurrence	Local recurrence of rectal cancer detected by clinical or radiological investigation	Five years after surgery

Collaborators and Investigators

• Sponsor: Umeå University
• Collaborators: The Swedish Society of Medicine; Västerbotten County Council, Sweden
• Investigators: Principal Investigator: Markku M Haapamäki, MD, PhD, Umeå University, Department of Surgical and Perioperative Sciences; Study Director: Jörgen Rutegård, MD, PhD, Umea University

Publications and helpful links

General Publications

• Holm T, Ljung A, Haggmark T, Jurell G, Lagergren J. Extended abdominoperineal resection with gluteus maximus flap reconstruction of the pelvic floor for rectal cancer. Br J Surg. 2007 Feb;94(2):232-8. doi: 10.1002/bjs.5489.
• Haapamaki MM, Pihlgren V, Lundberg O, Sandzen B, Rutegard J. Physical performance and quality of life after extended abdominoperineal excision of rectum and reconstruction of the pelvic floor with gluteus maximus flap. Dis Colon Rectum. 2011 Jan;54(1):101-6. doi: 10.1007/DCR.0b013e3181fce26e.
• Rutegard M, Rutegard J, Haapamaki MM. Multicentre, randomised trial comparing acellular porcine collagen implant versus gluteus maximus myocutaneous flap for reconstruction of the pelvic floor after extended abdominoperineal excision of rectum: study protocol for the Nordic Extended Abdominoperineal Excision (NEAPE) study. BMJ Open. 2019 May 29;9(5):e027255. doi: 10.1136/bmjopen-2018-027255.

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2011
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): September 30, 2024

Study Registration Dates

• First Submitted: May 3, 2011
• First Submitted That Met QC Criteria: May 3, 2011
• First Posted (Estimate): May 4, 2011

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: bioprosthesis; locomotion; surgical flaps; rectal neoplasms; reconstructive surgical procedure; lesser pelvis
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: NEAPE-2010-335-31M