Trial of Alvimopan in Major Spine Surgery

Constipation Clinical Trial

Official title:

Randomized, Double-Blind, Placebo-Controlled Trial of Alvimopan in Major Spine Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02789111
• Other study ID #: 18781
• Status: Completed
• Phase: Phase 4
• Start date: June 1, 2016
• Est. completion date: December 1, 2018

Study information

• Verified date: November 2020
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The Investigator has chosen to study the reconstructive spinal surgery patient population because it is believed that the use of alvimopan in these patients at the University of Virginia will give the scientific community significant insight into the broader applicability of this drug into other surgical populations, the impact of this drug on the perception of pain (as opposed to simply the consumption of opioids), and its impact on total hospital charges, resource utilization, and functional outcomes.

Description:

Pain control following major spine surgery is difficult to achieve. Opiates are often necessary in high doses, and may be associated with significant side effects. Such side effects may include urinary retention, altered mental status, depressed respiratory drive, and constipation, and may lead to reduced nutritional intake in the postoperative period. Importantly, post-operative nutrition may impact the incidence of complications following spine surgery.1 Alvimopan is a peripheral-acting opiate antagonist designed to decrease the gastrointestinal complications of perioperative systemic opioid administration. Pain control following major spine surgery is difficult to achieve. Opiates are often necessary in high doses, and may be associated with significant side effects including constipation. Alvimopan is a drug approved by the Food and Drug Administration (FDA) and is used to help the bowel recover more quickly in patients who are having bowel surgery, so that they can eat solid foods and have regular bowel movements. Alvimopan is in a class of medications called peripherally acting mu-opioid receptor antagonists. It works by protecting the bowel from the constipation effects of opioid (narcotic) medications that are used to treat pain after surgery. The purpose of this study is to determine if the use of alvimopan in major spine surgery reduces the time to first bowel movement. By assessing the use of alvimopan in reconstructive spinal surgery patients, researchers hope to give the scientific community insight into the broader use of this drug in other surgical populations, as well as gathering information on the impact of hospital charges and overall post-operative patient satisfaction.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: December 1, 2018
• Est. primary completion date: December 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Major spine surgery scheduled as part of clinical care
• 18-80 years

Exclusion Criteria:

• More than three doses of any opioid within one week of surgery
• Pregnancy
• Prisoners
• Unable to provide consent
• Emergency surgery
• Chronic kidney disease stage 5 (GFR < 15 ml/min)
• Severe hepatic impairment
• Recent myocardial infarction (within the last 3 months)

Related Conditions & MeSH terms

• Constipation

Intervention

Drug:
• Alvimopan
Alviimopan 12 mg twice daily up to 15 doses
• Placebo
Placebo twice daily up to 15 doses

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
University of Virginia	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (13)

Bell TJ, Poston SA, Kraft MD, Senagore AJ, Delaney CP, Techner L. Economic analysis of alvimopan in North American Phase III efficacy trials. Am J Health Syst Pharm. 2009 Aug 1;66(15):1362-8. doi: 10.2146/ajhp080329. — View Citation

Cortínez LI, Brandes V, Muñoz HR, Guerrero ME, Mur M. No clinical evidence of acute opioid tolerance after remifentanil-based anaesthesia. Br J Anaesth. 2001 Dec;87(6):866-9. — View Citation

Crawford MW, Hickey C, Zaarour C, Howard A, Naser B. Development of acute opioid tolerance during infusion of remifentanil for pediatric scoliosis surgery. Anesth Analg. 2006 Jun;102(6):1662-7. — View Citation

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. — View Citation

Fletcher D, Pinaud M, Scherpereel P, Clyti N, Chauvin M. The efficacy of intravenous 0.15 versus 0.25 mg/kg intraoperative morphine for immediate postoperative analgesia after remifentanil-based anesthesia for major surgery. Anesth Analg. 2000 Mar;90(3):666-71. — View Citation

Guignard B, Bossard AE, Coste C, Sessler DI, Lebrault C, Alfonsi P, Fletcher D, Chauvin M. Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology. 2000 Aug;93(2):409-17. — View Citation

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. Epub 2006 Apr 19. — View Citation

Lee LH, Irwin MG, Lui SK. Intraoperative remifentanil infusion does not increase postoperative opioid consumption compared with 70% nitrous oxide. Anesthesiology. 2005 Feb;102(2):398-402. — View Citation

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. — View Citation

Rauf K, Vohra A, Fernandez-Jimenez P, O'Keeffe N, Forrest M. Remifentanil infusion in association with fentanyl-propofol anaesthesia in patients undergoing cardiac surgery: effects on morphine requirement and postoperative analgesia. Br J Anaesth. 2005 Nov;95(5):611-5. Epub 2005 Sep 9. — View Citation

Stambough JL, Beringer D. Postoperative wound infections complicating adult spine surgery. J Spinal Disord. 1992 Sep;5(3):277-85. — View 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. Epub 2005 Dec 7. Erratum in: Surg Endosc. 2006 Mar;20(3):537. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to First Bowel Movement	time to first bowel movement after surgery	Time to event( up to 7 days); From date of day of surgery until the date of first documented bowel movement
Secondary	Time to Resumption of PO Intake	time to resumption oral intake after surgery	time to event ( up to 7 days); From date of day of surgery until the date of first documented PO intake