Colorectal anastomosis protected by a biodegradable drain fixed to the anastomosis by a circular stapler. A Multi-Center Randomized Controlled Trial (C-seal study)

The most important complication and cause of death following low anterior
resection (LAR) of the rectum is anastomotic leakage (5-20%). In many cases,
re-interventions are needed with creation of a stoma and/or drainage of an
abscess. To avoid serious complications like peritonitis and septic shock it is
important to prevent the occurrence of anastomotic leakage. Furthermore there
is an increasing use of preoperative radiotherapy in rectal cancer which may
cause additional problems in anastomotic healing.
Since the introduction of circular staplers in 1975, stapled low colorectal
anastomoses became routinely feasible. Stapled colorectal anastomoses have been
widely accepted as the standard approach to restore continuity after colorectal
resection.
The C-seal is a biodegradable thin-walled drain. It is compatible with the
circular stapler used in almost all LARs. It is developed to prevent
extravasation of intracolonic content to the peritoneal cavity. If the newly
created anastomosis shows dehiscence, the C-seal prevents leakage of feces
thereby preventing anastomotic leakage. The difference of the old Coloshield
compared to the C-seal is that the latter is completely biodegradable and is
attached into the lumen at the anastomosis during and by means of the standard
circular stapling procedure. This implies that the surgeon hardly has to alter
his technique. The drain degrades over time and disappears from the colon by
excretion through the anus. In 2006, the C-seal was first tested in 15 patients
undergoing LAR. The C-seal pilot study showed no anastomotic leakage. In 2010
the C-seal was tested in a multicenter phase II study. Thirty-seven patients
were treated with the C-seal and followed until 3 months post surgery. No
serious adverse events related to the C-seal use occurred. In 2 patients the
C-seal was incorrectly placed and could therefore not function properly. Both
patients recovered well without complications. One patient developed
anastomotic leakage leading to re-intervention within 30 days after the primary
surgery. Four patients had an abscess which spontaneously drained via the
rectum without a re-intervention. Two adverse events occurred during C-seal
application: The C-seal was stapled double at the anastomotic site and it was
not possible to extract the C-seal through the anus. The C-seal was cut loose
and the remaining part of the C-seal was left in situ. The C-seal did not exert
its function in these patients. Both patients recovered well without
complications.
To answer the question whether the C-seal is indeed helpful in preventing
anastomotic leakage necessitating re-intervention the current prospective
randomized controlled study will be performed.

Primary objective: efficacy of the C-seal in reducing anastomotic leakage (AL).
Secondary objectives: The number of dismantled anastomoses; AL within 30 days
according to the ISGRC classification; interval between the operation and AL;
The pain score at postoperative day 3; number of ostomies (also after 1 year);
late AL (diagnosed >=30 days and <1 year); total duration of hospital stay for
adverse events and/or stoma closure; Interval between C-seal application and
C-seal loss.

Multicenter randomized open phase III parallel group study.
Patient will be randomly allocated to either:
• Standard surgery.
• Standard surgery plus placement of C-seal.
Stratification acc. to centre, height of anastomosis and planned ostomy Y/N.
Follow-up until 1 year after surgery.
616 patients to be included.
Interim-analysis after 50 en 75% inclusion.

Standard surgery with or without placement of C-seal.

Risk: adverse events/complications of placement of C-seal.
Burden:
No extra visits.
Presence of C-seal until loss (normally <30 days).
Monitoring loss of C-seal.
VAS pain op 3rd postoperative day.