Resorbable Barrier for the Prevention of Abdominal and Peri-hepatic Adhesion Formation - Full Text View

Purpose

The purpose of this study is to evaluate the efficiency of a resorbable barrier membrane for the prevention of abdominal and peri-hepatic adhesion in patients with colorectal cancer requiring two-stage surgery for the resection of hepatic metastases.

Eligible patients will be randomly assigned to one of 2 arms:

Seprafilm group (receiving resorbable barrier membrane during the first surgery)
No-treatment control group (without seprafilm barrier during the first surgery)

The primary objective is to establish, in patients with colorectal cancer requiring two-stage surgery for the resection of hepatic metastases, the efficiency of a resorbable barrier membrane (Seprafilm) for limiting abdominal and peri-hepatic adhesion during the second operation.

This study is a prospective multicentric phase II, controlled, randomized and non comparative trial.

A total of 60 patients will be enrolled: 45 will receive Seprafilm whereas 15 will be assigned to the no-treatment control group. The inclusion period should be approximately 18 months. The follow up period after the second surgery will be 3 years.

Condition	Intervention	Phase
Colorectal Cancer	Procedure: - use of resorbable membrane Seprafilm Procedure: without resorbable barrier (seprafilm)	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	Evaluationof the Efficiency of a Resorbable Barrier Membrane for the Prevention of Abdominal and Peri-hepatic Adhesion in Patients With Colorectal Cancer Requiring Two-stage Surgery for the Resection of Hepatic Metastases

Resource links provided by NLM:

MedlinePlus related topics: Adhesions Cancer Colorectal Cancer

U.S. FDA Resources

Further study details as provided by Centre Leon Berard:

Primary Outcome Measures:

abdominal and peri-hepatic adhesion during the second operation [ Time Frame: Time to liberate liver (t0: incision and t1: liberation) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

immediate complications during the first surgical procedure in relation with operating procedure and use of resorbable membrane [ Time Frame: during the surgery ] [ Designated as safety issue: No ]
early complications (after the 1st surgical procedure)in relation with operating procedure and use of resorbable membrane [ Time Frame: during post-surgery hospitalization ] [ Designated as safety issue: No ]
late complications (after the 1st surgical procedure)in relation with operating procedure and use of resorbable membrane [ Time Frame: between 1st and 2nd surgeries (2 operations should be scheduled at an interval of 1 to 6 months) ] [ Designated as safety issue: No ]
abdominal and peri-hepatic adhesion (at the site of the 1st surgery), with qualitative and quantitative description [ Time Frame: at the beginning of the 2nd surgical procedure ] [ Designated as safety issue: No ]
intestinal adhesion (in the small intestine), with quantitative description [ Time Frame: at the beginning of the second surgical procedure ] [ Designated as safety issue: No ]
immediate complications in relation with operating procedure. [ Time Frame: during the 2nd surgical procedure ] [ Designated as safety issue: No ]
early complications (after 2ng operation) in relation with operating procedure. [ Time Frame: during post-surgery hospitalization ] [ Designated as safety issue: No ]
late complications in relation with operating procedure. [ Time Frame: in the month following the 2nd intervention ] [ Designated as safety issue: No ]
post-operative rehabilitation [ Time Frame: during post-surgery hospitalization ] [ Designated as safety issue: No ]
tumour evolution in patients [ Time Frame: over a period of 3 years after the 2nd surgery ] [ Designated as safety issue: No ]

Enrollment:	60
Study Start Date:	July 2008
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: - Seprafilm group patients receiving resorbable barrier membrane during the first surgery	Procedure: - use of resorbable membrane Seprafilm use of resorbable membrane during the first surgery for the resection of hepatic metastases, 1 to 4 membranes should be used around the liver Other Name: use of Seprafilm after the resction of hepatic metastases
- No-treatment control group patients without seprafilm barrier during the first surgery	Procedure: without resorbable barrier (seprafilm) non use of resorbable membrane during the first surgery for the resection of hepatic metastases Other Name: resection of hepatic metastases

Detailed Description:

The secondary objectives of the study are:

During and after the 1st surgical procedure To evaluate immediate complications (during surgery), early complications (during post-surgery hospitalization) and late complications (between 1st and 2nd surgeries) in relation with operating procedure and use of resorbable membrane.

During and after the 2nd surgical procedure

To evaluate abdominal and peri-hepatic adhesion (at the site of the 1st surgery), with qualitative and quantitative description.
To evaluate intestinal adhesion (in the small intestine), with quantitative description.
To evaluate immediate complications (during surgery), early complications (during post-surgery hospitalization) and late complications (in the month following the intervention) in relation with operating procedure.
To evaluate post-operative rehabilitation
To assess tumour evolution in patients over a period of 3 years after the 2nd surgery.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Women and men aged ≥ 18 years
Colorectal cancer with synchronous or metachronous hepatic metastases
Patients requiring two-stage surgery with laparotomy for the resection of hepatic metastases
The 2 operations should be scheduled in the same centre
The 2 operations should be scheduled at an interval of 1 to 6 months
Patient affiliated with social security
Patient able to read and write French
Written, voluntary, informed consent

Exclusion Criteria:

Patient with previous hepatic or biliary surgery through supra-umbilical incision (except biliary surgery with laparotomy more than 6 months previously)
Patient with previous major surgery except colorectal surgery for resection of primitive tumour
Metastasis removable in one surgical procedure
Non resectable metastasis
Follow-up impossible for social, geographical, familial or psychological reasons
Patient deprived of freedom
Patient enrolled in another experimental surgery trial
Pregnant or lactating woman

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01262417

Locations

France
Institut Bergonié
Bordeaux, France, 33076
Hôpital Antoine Béclère
Clamart, France
CHU Clermont Ferrand
Clermont Ferrand, France
Hôpital Beaujon
Clichy, France
CHU Grenoble
Grenoble, France
Hôpital de La Croix Rousse
Lyon, France
Centre Léon Bérard
Lyon, France
Centre Hospitalier Lyon Sud
Lyon, France
Institut Paoli Calmettes
Marseille, France
CHU La conception
Marseille, France
Centre Val d'Aurelle Paul Lamarque
Montpellier, France
Hôpital de Brabois CHU
Nancy, France
Centre Alexis Vautrin
Nancy, France
CHU Nice-Hôpital de l'Archet II
Nice, France
Hôpital Cochin
Paris, France
Hôpital Charles Nicolle - CHU Rouen
Rouen, France
Institut Gustave Roussy
Villejuif, France

Sponsors and Collaborators

Centre Leon Berard

Ministry of Health, France

Investigators

Principal Investigator:

Michel Rivoire, MD

Centre Léon Bérard, Lyon

More Information

Publications:

Weibel MA, Majno G. Peritoneal adhesions and their relation to abdominal surgery. A postmortem study. Am J Surg. 1973 Sep;126(3):345-53. No abstract available.

Adam R, Laurent A, Azoulay D, Castaing D, Bismuth H. Two-stage hepatectomy: A planned strategy to treat irresectable liver tumors. Ann Surg. 2000 Dec;232(6):777-85.

Jaeck D, Oussoultzoglou E, Rosso E, Greget M, Weber JC, Bachellier P. A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases. Ann Surg. 2004 Dec;240(6):1037-49; discussion 1049-51.

Ellis H, Moran BJ, Thompson JN, Parker MC, Wilson MS, Menzies D, McGuire A, Lower AM, Hawthorn RJ, O'Brien F, Buchan S, Crowe AM. Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort study. Lancet. 1999 May 1;353(9163):1476-80.

Beck DE, Opelka FG, Bailey HR, Rauh SM, Pashos CL. Incidence of small-bowel obstruction and adhesiolysis after open colorectal and general surgery. Dis Colon Rectum. 1999 Feb;42(2):241-8. Erratum in: Dis Colon Rectum 1999 May;42(5):578.

Diamond MP, Freeman ML. Clinical implications of postsurgical adhesions. Hum Reprod Update. 2001 Nov-Dec;7(6):567-76. Review.

Ray NF, Denton WG, Thamer M, Henderson SC, Perry S. Abdominal adhesiolysis: inpatient care and expenditures in the United States in 1994. J Am Coll Surg. 1998 Jan;186(1):1-9.

Lower AM, Hawthorn RJ, Ellis H, O'Brien F, Buchan S, Crowe AM. The impact of adhesions on hospital readmissions over ten years after 8849 open gynaecological operations: an assessment from the Surgical and Clinical Adhesions Research Study. BJOG. 2000 Jul;107(7):855-62.

Lower AM, Hawthorn RJ, Clark D, Boyd JH, Finlayson AR, Knight AD, Crowe AM; Surgical and Clinical Research (SCAR) Group. Adhesion-related readmissions following gynaecological laparoscopy or laparotomy in Scotland: an epidemiological study of 24 046 patients. Hum Reprod. 2004 Aug;19(8):1877-85. Epub 2004 Jun 3.

Parker MC, Ellis H, Moran BJ, Thompson JN, Wilson MS, Menzies D, McGuire A, Lower AM, Hawthorn RJ, O'Briena F, Buchan S, Crowe AM. Postoperative adhesions: ten-year follow-up of 12,584 patients undergoing lower abdominal surgery. Dis Colon Rectum. 2001 Jun;44(6):822-29; discussion 829-30.

Parker MC. Epidemiology of adhesions: the burden. Hosp Med. 2004 Jun;65(6):330-6. Review.

Bristow RE, Montz FJ. Prevention of adhesion formation after radical oophorectomy using a sodium hyaluronate-carboxymethylcellulose (HA-CMC) barrier. Gynecol Oncol. 2005 Nov;99(2):301-8. Epub 2005 Aug 8.

Bristow RE, Santillan A, Diaz-Montes TP, Gardner GJ, Giuntoli RL 2nd, Peeler ST. Prevention of adhesion formation after radical hysterectomy using a sodium hyaluronate-carboxymethylcellulose (HA-CMC) barrier: a cost-effectiveness analysis. Gynecol Oncol. 2007 Mar;104(3):739-46. Epub 2006 Nov 13.

Duron JJ. [Post-operative bowel obstruction. Part 2: Mechanical post-operative small bowel obstruction by bands and adhesions]. J Chir (Paris). 2003 Dec;140(6):325-34. Review. French.

Duron JJ. [Post-operative bowel obstruction. Part 1: Intraperitoneal bands and adhesions--causes and prevention]. J Chir (Paris). 2003 Sep;140(4):211-9. Review. French.

Cuervas-Mons V, Rimola A, Van Thiel DH, Gavaler JS, Schade RR, Starzl TE. Does previous abdominal surgery alter the outcome of pediatric patients subjected to orthotopic liver transplantation? Gastroenterology. 1986 Apr;90(4):853-7.

Sandler AD, Azarow KS, Superina RA. The impact of a previous Kasai procedure on liver transplantation for biliary atresia. J Pediatr Surg. 1997 Mar;32(3):416-9.

Ong TH. Prevention of intraabdominal adhesions in Kasai portoenterostomy. J Pediatr Surg. 2001 Nov;36(11):1613-4.

Jaeck D, Bachellier P, Guiguet M, Boudjema K, Vaillant JC, Balladur P, Nordlinger B. Long-term survival following resection of colorectal hepatic metastases. Association Française de Chirurgie. Br J Surg. 1997 Jul;84(7):977-80.

Rivoire M; ANAES. [Can initially non-respectable hepatic metastases be made resectable?]. Gastroenterol Clin Biol. 2003 Mar;27 Spec No 2:B18-9, B88-104. French. No abstract available.

Al-Jaroudi D, Tulandi T. Adhesion prevention in gynecologic surgery. Obstet Gynecol Surv. 2004 May;59(5):360-7. Review.

Beck DE, Cohen Z, Fleshman JW, Kaufman HS, van Goor H, Wolff BG; Adhesion Study Group Steering Committee. A prospective, randomized, multicenter, controlled study of the safety of Seprafilm adhesion barrier in abdominopelvic surgery of the intestine. Dis Colon Rectum. 2003 Oct;46(10):1310-9.

Becker JM, Dayton MT, Fazio VW, Beck DE, Stryker SJ, Wexner SD, Wolff BG, Roberts PL, Smith LE, Sweeney SA, Moore M. Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double-blind multicenter study. J Am Coll Surg. 1996 Oct;183(4):297-306.

Diamond MP. Reduction of adhesions after uterine myomectomy by Seprafilm membrane (HAL-F): a blinded, prospective, randomized, multicenter clinical study. Seprafilm Adhesion Study Group. Fertil Steril. 1996 Dec;66(6):904-10.

Salum MR, Lam DT, Wexner SD, Pikarsky A, Baig MK, Weiss EG, Nogueras JJ, Singh JJ. Does limited placement of bioresorbable membrane of modified sodium hyaluronate and carboxymethylcellulose (Seprafilm) have possible short-term beneficial impact? Dis Colon Rectum. 2001 May;44(5):706-12.

Tang CL, Seow-Choen F, Fook-Chong S, Eu KW. Bioresorbable adhesion barrier facilitates early closure of the defunctioning ileostomy after rectal excision: a prospective, randomized trial. Dis Colon Rectum. 2003 Sep;46(9):1200-7.

Vrijland WW, Tseng LN, Eijkman HJ, Hop WC, Jakimowicz JJ, Leguit P, Stassen LP, Swank DJ, Haverlag R, Bonjer HJ, Jeekel H. Fewer intraperitoneal adhesions with use of hyaluronic acid-carboxymethylcellulose membrane: a randomized clinical trial. Ann Surg. 2002 Feb;235(2):193-9.

Tingstedt B, Isaksson K, Andersson E, Andersson R. Prevention of abdominal adhesions--present state and what's beyond the horizon? Eur Surg Res. 2007;39(5):259-68. Epub 2007 May 10. Review.

Oikonomakis I, Wexner SD, Gervaz P, You SY, Secic M, Giamundo P. Seprafilm: a retrospective preliminary evaluation of the impact on short-term oncologic outcome in colorectal cancer. Dis Colon Rectum. 2002 Oct;45(10):1376-80.

Kusunoki M, Ikeuchi H, Yanagi H, Noda M, Tonouchi H, Mohri Y, Uchida K, Inoue Y, Kobayashi M, Miki C, Yamamura T. Bioresorbable hyaluronate-carboxymethylcellulose membrane (Seprafilm) in surgery for rectal carcinoma: a prospective randomized clinical trial. Surg Today. 2005;35(11):940-5.

Wieand HS. Randomized phase II trials: what does randomization gain? J Clin Oncol. 2005 Mar 20;23(9):1794-5. Epub 2005 Feb 7. No abstract available.

Dixon WJ, Massey FJ. Introduction to statistical analysis. 4th Edition McGraw-Hill, 1983; 80-5.

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Responsible Party:	Zora ABDELBOST, Centre Léon Bérard, 28 rue Laënnec, 69373, Lyon
ClinicalTrials.gov Identifier:	NCT01262417 History of Changes
Other Study ID Numbers:	SEPRAC2T
Study First Received:	December 15, 2010
Last Updated:	December 16, 2010
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Leon Berard:

colorectal cancer
two stage surgery for the resection of hepatic metastases
resorbable barrier membrane
abdominal and peri-hepatic adhesion

Additional relevant MeSH terms:

Tissue Adhesions
Colorectal Neoplasms
Cicatrix
Fibrosis
Pathologic Processes
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms

Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on May 23, 2013

Resorbable Barrier for the Prevention of Abdominal and Peri-hepatic Adhesion Formation (SEPRAC2T)