Clinical trial NCT00388479: Study of Alvimopan for the Management of Opioid-induced Postoperative Bowel Dysfunction/ Postoperative Ileus
Official title: A Multicenter Phase III, Double-Blind, Placebo-Controlled, Parallel Study of ADL-8-2698 in Opioid-Induced Postoperative Bowel Dysfunction/Postoperative Ileus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ileus
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2006-10-16
Enrollment: 666
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients undergoing major abdominal surgery are at highest risk for developing postoperative ileus (POI), occurring in nearly all cases. Signs and symptoms of POI may include abdominal distention and bloating, persistent abdominal pain; nausea and/or vomiting; delayed passage or inability to pass flatus or stool; and inability to tolerate a solid diet. This study will test the ability of alvimopan 6 mg or 12 mg given 2 hours before the scheduled start of surgery to hasten the recovery of GI function in patients undergoing major abdominal surgery (bowel resection or abdominal hysterectomy).

Detailed description: Postoperative ileus (POI) is a temporary slowing down or stopping of bowel function and a slowing down of movement of contents of the intestines. This functional impairment persists for a variable duration following surgery, usually resolving within 1 day in the small intestine, 1 to 3 days in the stomach and 3 to 5 days in the colon. When POI persists for more than 5 days, it is generally considered severe, sometimes referred to as complicated or prolonged POI, and increases the risk for related morbidity. No drug therapy has been shown to consistently shorten the duration of POI. This study is designed to demonstrate that alvimopan, a novel, peripherally acting mu opioid receptor antagonist, accelerates the recovery of GI function in patients undergoing bowel resection or hysterectomy.

Eligibility criteria: Inclusion Criteria:

* Subject is scheduled for a partial small/large bowel resection with primary anastomosis or total abdominal hysterectomy (simple or radical) via laparotomy
* Subject is scheduled to receive primary postoperative pain management with intravenous (i.v.) patient-controlled analgesia (PCA) opioids

Exclusion Criteria:

* Subject is scheduled for a total colectomy, colostomy, ileostomy
* Subject has complete bowel obstruction
* Subject has recently been on an acute course (1-10 days) of opioid analgesics and has not been off all opioids for at least 1 week prior to surgery Subject has been on chronic (\>10 days) opioid analgesics and has not been off all opioids for at least 2 weeks prior to surgery.

Primary outcomes:
measure: Acceleration of gastrointestinal recovery
Secondary outcomes:
measure: Time until ready for discharge based upon recovery of GI function
measure: Severity of GI symptoms
measure: Pain
measure: Opioid Consumption
measure: Time to tolerate liquids
measure: Need for reinsertion of nasogastric tube
measure: Time until discharge order is written
Other outcomes:
Locations:
city: Exton
country: United States
facility: Various
state: Pennsylvania
Study officials:
affiliation: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
name: Adolor Corporation
role: STUDY_DIRECTOR
References:
citation: Viscusi ER, Goldstein S, Witkowski T, Andonakakis A, Jan R, Gabriel K, Du W, Techner L, Wallin B. Alvimopan, a peripherally acting mu-opioid receptor antagonist, compared with placebo in postoperative ileus after major abdominal surgery: results of a randomized, double-blind, controlled study. Surg Endosc. 2006 Jan;20(1):64-70. doi: 10.1007/s00464-005-0104-y. Epub 2005 Dec 7.
citation: Ludwig K, Viscusi ER, Wolff BG, Delaney CP, Senagore A, Techner L. Alvimopan for the management of postoperative ileus after bowel resection: characterization of clinical benefit by pooled responder analysis. World J Surg. 2010 Sep;34(9):2185-90. doi: 10.1007/s00268-010-0635-9.