Alvimopan Use in Polytraumatized Patients

NCT03068975 | Terminated Phase 4 DMC FDA Drug

• 1 other identifier: 55238
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy and safety of Alvimopan(12 mg) in recovery of bowel function in an emergency trauma setting without the pre-operative dosage in patients that will receive abdominal surgery.

Conditions

Post Operative Ileus

Outcome Measures

Primary Outcomes (1)

• Recovery of bowel function in trauma patients who received post operative dose of Alvimopan compared to placebo.

  Since Entereg is a peripherally opioid receptor antagonist it will bind to those receptors and will avoid the post operative ileus hence the bowel recovery will be faster. By physical examination (passage of flatus, bowel movements upon auscultation) will be used to assess recovery of bowel function

  2 years

Secondary Outcomes (1)

• Length of stay in patients of the same population who receive a placebo.

  5 years

Study Arms (2)

Alvimopan

EXPERIMENTAL

Patients in the study group will be administered a post operative dose of Alvimopan

Drug: Alvimopan

Placebo

PLACEBO COMPARATOR

Patients in the Placebo group will receive a placebo pill and will be compared with the study group

Drug: Placebo

Interventions

Alvimopan DRUG

Patients who sustained abdominal trauma with resection of bowel and anastomosis will receive Alvimopan ( post operative dose only) and will monitor for post operative ileus.

Also known as: Entereg

Alvimopan

Placebo DRUG

Patients who sustained abdominal trauma with resection of bowel and anastomosis will receive the Placebo Pill (post operative dose only) and will monitor for post operative ileus.

Also known as: placebo pill

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18 to 80
• Poly-traumatized patients
• Extubated patients after abdominal exploration
• Underwent Abdominal exploration, had colon resection with primary anastomosis with closure of abdomen

You may not qualify if:

• Mechanically ventilated patients
• Patient not expected to survive Glasgow Coma Scale = 3
• Pregnant patients
• Apache score \> 40 (observed mortality 100%) Saas Ahmed Naved et al 2011
• Vasopressor therapy
• Septic patients
• Thoracotomy
• Bogota bag
• Intravenous Drug Abuser (IVDA) as evidenced by urine toxicology upon admission to the Trauma Unit
• Patients with prior history of gastric surgery and/or colonic surgery
• Medical History: of severe cardiovascular disease, Renal diseases, Hepatitis C or Hepatic failure, Autoimmune disease, Crohn and Ulcerative Colitis (In view of the inflammation in the intestinal mucosal which may decrease optimal absorption of the medication) and or bowel obstruction
• Prior pancreatic anastomosis or gastric anastomosis; ostomy formation
• Chronic use of nonsteroidal anti-inflammatory drugs

Sponsors & Collaborators

• University of Puerto Rico: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Puerto Rico Trauma Hospital

San Juan, US, 00922, Puerto Rico

Location

Related Publications (18)

• Bragg D, El-Sharkawy AM, Psaltis E, Maxwell-Armstrong CA, Lobo DN. Postoperative ileus: Recent developments in pathophysiology and management. Clin Nutr. 2015 Jun;34(3):367-76. doi: 10.1016/j.clnu.2015.01.016. Epub 2015 Jan 31.

  PMID: 25819420 BACKGROUND

• Delaney CP, Weese JL, Hyman NH, Bauer J, Techner L, Gabriel K, Du W, Schmidt WK, Wallin BA; Alvimopan Postoperative Ileus Study Group. Phase III trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery. Dis Colon Rectum. 2005 Jun;48(6):1114-25; discussion 1125-6; author reply 1127-9. doi: 10.1007/s10350-005-0035-7.

  PMID: 15906123 BACKGROUND

• Delaney CP, Senagore AJ, Viscusi ER, Wolff BG, Fort J, Du W, Techner L, Wallin B. Postoperative upper and lower gastrointestinal recovery and gastrointestinal morbidity in patients undergoing bowel resection: pooled analysis of placebo data from 3 randomized controlled trials. Am J Surg. 2006 Mar;191(3):315-9. doi: 10.1016/j.amjsurg.2005.10.026.

  PMID: 16490538 BACKGROUND

• Earnshaw SR, Kauf TL, McDade C, Potashman MH, Pauyo C, Reese ES, Senagore A. Economic Impact of Alvimopan Considering Varying Definitions of Postoperative Ileus. J Am Coll Surg. 2015 Nov;221(5):941-50. doi: 10.1016/j.jamcollsurg.2015.08.004. Epub 2015 Aug 15.

  PMID: 26353904 BACKGROUND

• Hilton WM, Lotan Y, Parekh DJ, Basler JW, Svatek RS. Alvimopan for prevention of postoperative paralytic ileus in radical cystectomy patients: a cost-effectiveness analysis. BJU Int. 2013 Jun;111(7):1054-60. doi: 10.1111/j.1464-410X.2012.11499.x. Epub 2012 Nov 21.

  PMID: 23171223 BACKGROUND

• Herzog TJ, Coleman RL, Guerrieri JP Jr, Gabriel K, Du W, Techner L, Fort JG, Wallin B. A double-blind, randomized, placebo-controlled phase III study of the safety of alvimopan in patients who undergo simple total abdominal hysterectomy. Am J Obstet Gynecol. 2006 Aug;195(2):445-53. doi: 10.1016/j.ajog.2006.01.039. Epub 2006 Apr 19.

  PMID: 16626607 BACKGROUND

• Holte K, Kehlet H. Postoperative ileus: a preventable event. Br J Surg. 2000 Nov;87(11):1480-93. doi: 10.1046/j.1365-2168.2000.01595.x.

  PMID: 11091234 BACKGROUND

• Kalff JC, Schraut WH, Simmons RL, Bauer AJ. Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus. Ann Surg. 1998 Nov;228(5):652-63. doi: 10.1097/00000658-199811000-00004.

  PMID: 9833803 BACKGROUND

• 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.

  PMID: 20526599 BACKGROUND

• Ludwig K, Enker WE, Delaney CP, Wolff BG, Du W, Fort JG, Cherubini M, Cucinotta J, Techner L. Gastrointestinal tract recovery in patients undergoing bowel resection: results of a randomized trial of alvimopan and placebo with a standardized accelerated postoperative care pathway. Arch Surg. 2008 Nov;143(11):1098-105. doi: 10.1001/archsurg.143.11.1098.

  PMID: 19015469 BACKGROUND

• Manger JP, Nelson M, Blanchard S, Helo S, Conaway M, Krupski TL. Alvimopan: A cost-effective tool to decrease cystectomy length of stay. Cent European J Urol. 2014;67(4):335-41. doi: 10.5173/ceju.2014.04.art4. Epub 2014 Dec 5.

  PMID: 25667750 BACKGROUND

• Miedema BW, Johnson JO. Methods for decreasing postoperative gut dysmotility. Lancet Oncol. 2003 Jun;4(6):365-72. doi: 10.1016/s1470-2045(03)01118-5.

  PMID: 12788410 BACKGROUND

• Naved SA, Siddiqui S, Khan FH. APACHE-II score correlation with mortality and length of stay in an intensive care unit. J Coll Physicians Surg Pak. 2011 Jan;21(1):4-8.

  PMID: 21276376 BACKGROUND

• Simorov A, Thompson J, Oleynikov D. Alvimopan reduces length of stay and costs in patients undergoing segmental colonic resections: results from multicenter national administrative database. Am J Surg. 2014 Dec;208(6):919-25; discussion 925. doi: 10.1016/j.amjsurg.2014.08.011. Epub 2014 Sep 22.

  PMID: 25440479 BACKGROUND

• Thompson M, Magnuson B. Management of postoperative ileus. Orthopedics. 2012 Mar;35(3):213-7. doi: 10.3928/01477447-20120222-08.

  PMID: 22385598 BACKGROUND

• Vaughan-Shaw PG, Fecher IC, Harris S, Knight JS. A meta-analysis of the effectiveness of the opioid receptor antagonist alvimopan in reducing hospital length of stay and time to GI recovery in patients enrolled in a standardized accelerated recovery program after abdominal surgery. Dis Colon Rectum. 2012 May;55(5):611-20. doi: 10.1097/DCR.0b013e318249fc78.

  PMID: 22513441 BACKGROUND

• Winegar B, Cox M, Truelove D, Brock G, Scherrer N, Pass LA. Efficacy of alvimopan following bowel resection: a comparison of two dosing strategies. Ann Pharmacother. 2013 Nov;47(11):1406-13. doi: 10.1177/1060028013504289.

  PMID: 24285757 BACKGROUND

• Wolff BG, Michelassi F, Gerkin TM, Techner L, Gabriel K, Du W, Wallin BA; Alvimopan Postoperative Ileus Study Group. Alvimopan, a novel, peripherally acting mu opioid antagonist: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial of major abdominal surgery and postoperative ileus. Ann Surg. 2004 Oct;240(4):728-34; discussion 734-5. doi: 10.1097/01.sla.0000141158.27977.66.

  PMID: 15383800 BACKGROUND

MeSH Terms

Interventions

alvimopan

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: Will create a double blind, randomized, parallel design study to evaluate the effectiveness of Alvimopan(post operative dose) in preventing post-operative ileus in poly-traumatized patients

Study Record Dates

• First Submitted: February 17, 2017
• First Posted: March 3, 2017
• Study Start: September 1, 2017
• Primary Completion: November 19, 2019
• Study Completion: November 19, 2019
• Last Updated: February 5, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share

Locations

PR (1)