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

NCT01262417 | Completed Phase 2 DMC

• 1 other identifier: SEPRAC2T
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 17

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• abdominal and peri-hepatic adhesion during the second operation

  Time to liberate liver (t0: incision and t1: liberation)

Secondary Outcomes (10)

• immediate complications during the first surgical procedure in relation with operating procedure and use of resorbable membrane

  during the surgery

• early complications (after the 1st surgical procedure)in relation with operating procedure and use of resorbable membrane

  during post-surgery hospitalization

• late complications (after the 1st surgical procedure)in relation with operating procedure and use of resorbable membrane

  between 1st and 2nd surgeries (2 operations should be scheduled at an interval of 1 to 6 months)

• abdominal and peri-hepatic adhesion (at the site of the 1st surgery), with qualitative and quantitative description

  at the beginning of the 2nd surgical procedure

• intestinal adhesion (in the small intestine), with quantitative description

  at the beginning of the second surgical procedure

Study Arms (2)

- Seprafilm group

EXPERIMENTAL

patients receiving resorbable barrier membrane during the first surgery

Procedure: - use of resorbable membrane Seprafilm

- No-treatment control group

OTHER

patients without seprafilm barrier during the first surgery

Procedure: without resorbable barrier (seprafilm)

Interventions

- use of resorbable membrane Seprafilm PROCEDURE

use of resorbable membrane during the first surgery for the resection of hepatic metastases, 1 to 4 membranes should be used around the liver

Also known as: use of Seprafilm after the resction of hepatic metastases

- Seprafilm group

without resorbable barrier (seprafilm) PROCEDURE

non use of resorbable membrane during the first surgery for the resection of hepatic metastases

Also known as: resection of hepatic metastases

- No-treatment control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Leon Berard: lead
• Ministry of Health, France: collaborator

Study Sites (17)

Institut Bergonié

Bordeaux, 33076, France

Location

Hôpital Antoine Béclère

Clamart, France

Location

CHU Clermont Ferrand

Clermont-Ferrand, France

Location

Hôpital Beaujon

Clichy, France

Location

CHU Grenoble

Grenoble, France

Location

Centre Hospitalier Lyon Sud

Lyon, France

Location

Centre Léon Bérard

Lyon, France

Location

Hôpital de La Croix Rousse

Lyon, France

Location

CHU La conception

Marseille, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Centre Val d'Aurelle Paul Lamarque

Montpellier, France

Location

Centre Alexis Vautrin

Nancy, France

Location

Hôpital de Brabois CHU

Nancy, France

Location

CHU Nice-Hôpital de l'Archet II

Nice, France

Location

Hôpital Cochin

Paris, France

Location

Hôpital Charles Nicolle - CHU Rouen

Rouen, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Related Publications (34)

• Weibel MA, Majno G. Peritoneal adhesions and their relation to abdominal surgery. A postmortem study. Am J Surg. 1973 Sep;126(3):345-53. doi: 10.1016/s0002-9610(73)80123-0. No abstract available.

  PMID: 4580750 BACKGROUND

• 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. doi: 10.1097/00000658-200012000-00006.

  PMID: 11088072 BACKGROUND

• 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. doi: 10.1097/01.sla.0000145965.86383.89.

  PMID: 15570209 BACKGROUND

• 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. doi: 10.1016/S0140-6736(98)09337-4.

  PMID: 10232313 BACKGROUND

• 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. doi: 10.1007/BF02237135. Erratum In: Dis Colon Rectum 1999 May;42(5):578.

  PMID: 10211502 BACKGROUND

• Diamond MP, Freeman ML. Clinical implications of postsurgical adhesions. Hum Reprod Update. 2001 Nov-Dec;7(6):567-76. doi: 10.1093/humupd/7.6.567.

  PMID: 11727865 BACKGROUND

• 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. doi: 10.1016/s1072-7515(97)00127-0.

  PMID: 9449594 BACKGROUND

• 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. doi: 10.1111/j.1471-0528.2000.tb11083.x.

  PMID: 10901556 BACKGROUND

• 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. doi: 10.1093/humrep/deh321. Epub 2004 Jun 3.

  PMID: 15178659 BACKGROUND

• 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. doi: 10.1007/BF02234701.

  PMID: 11391142 BACKGROUND

• Parker MC. Epidemiology of adhesions: the burden. Hosp Med. 2004 Jun;65(6):330-6. doi: 10.12968/hosp.2004.65.6.13729.

  PMID: 15222206 BACKGROUND

• 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. doi: 10.1016/j.ygyno.2005.06.057. Epub 2005 Aug 8.

  PMID: 16085295 BACKGROUND

• 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. doi: 10.1016/j.ygyno.2006.09.029. Epub 2006 Nov 13.

  PMID: 17097723 BACKGROUND

• 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. French.

  PMID: 14978440 BACKGROUND

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

  PMID: 13679770 BACKGROUND

• 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. doi: 10.1016/0016-5085(86)90860-7.

  PMID: 3512356 BACKGROUND

• 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. doi: 10.1016/s0022-3468(97)90594-7.

  PMID: 9094006 BACKGROUND

• Ong TH. Prevention of intraabdominal adhesions in Kasai portoenterostomy. J Pediatr Surg. 2001 Nov;36(11):1613-4. doi: 10.1053/jpsu.2001.27930.

  PMID: 11685684 BACKGROUND

• Jaeck D, Bachellier P, Guiguet M, Boudjema K, Vaillant JC, Balladur P, Nordlinger B. Long-term survival following resection of colorectal hepatic metastases. Association Francaise de Chirurgie. Br J Surg. 1997 Jul;84(7):977-80. doi: 10.1002/bjs.1800840719.

  PMID: 9240140 BACKGROUND

• 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. No abstract available. French.

  PMID: 12637875 BACKGROUND

• Al-Jaroudi D, Tulandi T. Adhesion prevention in gynecologic surgery. Obstet Gynecol Surv. 2004 May;59(5):360-7. doi: 10.1097/00006254-200405000-00024.

  PMID: 15097797 BACKGROUND

• 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. doi: 10.1007/s10350-004-6739-2.

  PMID: 14530667 BACKGROUND

• 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.

  PMID: 8843257 BACKGROUND

• 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.

  PMID: 8941053 BACKGROUND

• 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. doi: 10.1007/BF02234571.

  PMID: 11357033 BACKGROUND

• 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. doi: 10.1007/s10350-004-6716-9.

  PMID: 12972964 BACKGROUND

• 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. doi: 10.1097/00000658-200202000-00006.

  PMID: 11807358 BACKGROUND

• 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. doi: 10.1159/000102591. Epub 2007 May 10.

  PMID: 17495476 BACKGROUND

• 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. doi: 10.1007/s10350-004-6428-1.

  PMID: 12394438 BACKGROUND

• 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. doi: 10.1007/s00595-005-3061-0.

  PMID: 16249848 BACKGROUND

• Wieand HS. Randomized phase II trials: what does randomization gain? J Clin Oncol. 2005 Mar 20;23(9):1794-5. doi: 10.1200/JCO.2005.10.956. Epub 2005 Feb 7. No abstract available.

  PMID: 15699476 BACKGROUND

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

  BACKGROUND

• Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457-81.

  BACKGROUND

• Dupre A, Lefranc A, Buc E, Delpero JR, Quenet F, Passot G, Evrard S, Rivoire M. Use of bioresorbable membranes to reduce abdominal and perihepatic adhesions in 2-stage hepatectomy of liver metastases from colorectal cancer: results of a prospective, randomized controlled phase II trial. Ann Surg. 2013 Jul;258(1):30-6. doi: 10.1097/SLA.0b013e3182854949.

  PMID: 23426344 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Seprafilm

Condition Hierarchy (Ancestors)

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

Study Officials

• Michel Rivoire, MD

  Centre Léon Bérard, Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 15, 2010
• First Posted: December 17, 2010
• Study Start: July 1, 2008
• Primary Completion: November 1, 2010
• Last Updated: December 17, 2010

Record last verified: 2010-05

Locations

FR (17)