Study of Prevention of Postoperative Nausea and Vomiting Using Cesamet

NCT02115529 | Completed Phase 2 DMC

• 1 other identifier: 13-242
• Study Type: interventional
• Target: 331
• Locations: 1 country
• Sites: 1

Brief Summary

Untreated, one third of patients undergoing general anesthesia will have postoperative nausea, vomiting, or both. Patients often rate postoperative nausea and vomiting (PONV) as worse than postoperative pain. PONV increases the risk of aspiration and has been associated with suture dehiscence, esophageal rupture, subcutaneous emphysema, and bilateral pneumothoraxes. PONV frequently delays discharge, and is the leading cause of unexpected hospital admission after planned ambulatory surgery. Nabilone (Cesamet®) is a synthetic cannabinoid developed in the 1970s which is a potent CB1 agonist. The use of nabilone in preventing nausea and vomiting in patients receiving chemotherapy has been thoroughly investigated. Results from clinical studies demonstrated the efficacy, safety, and tolerability of Cesamet in this population. There has been success in the past translating treatments for chemotherapy-induced nausea and vomiting (ie. 5-HT receptor agonists including Ondansetron and Granisetron) to use in the perioperative environment. Only one RCT has studied the use of nabilone for the reduction of PONV. Published in 1995, this study compared the administration of either Cesamet 2 mg or metoclopramide 10 mg given 90 minutes before the operation in patients scheduled for elective hysterectomy in 60 women. This study failed to show any significant difference between groups. There are several limitations to this study including a poorly optimized dosing regimen, a small sample size, and a comparison group lacking clinical generalizability. This study will investigate the use Cesamet vs Placebo, in addition to the regular antiemetic treatment which patients receive at the discretion of the managing anesthesiologist, for the prevention of PONV. The study group will include patients undergoing general anesthesia for elective ambulatory surgery with at least 3 risk factors (\>60% risk) for the development of PONV.

Conditions

Postoperative Nausea and Vomiting

Outcome Measures

Primary Outcomes (1)

• Incidence of postoperative nausea and/or vomiting

  Prior to discharge from postanesthesia care unit, an expected average of two hours

Secondary Outcomes (1)

• Number of antiemetic rescue medications given postoperatively.

  Prior to discharge from postanesthesia care unit, an expected average of two hours

Other Outcomes (7)

• Standardized score of nausea and/or vomiting severity if PONV occurs.

  Prior to discharge from postanesthesia care unit, an expected average of two hours

• Pain score during the immediate post-operative period.

  Prior to discharge from postanesthesia care unit, an expected average of two hours

• Use of intraoperative and postoperative opioids

  Prior to discharge from postanesthesia care unit, an expected average of two hours

Study Arms (2)

Cesamet (nabilone)

ACTIVE COMPARATOR

0.5 mg capsule containing Cesamet (single dose) given preoperatively

Drug: Nabilone

Placebo

PLACEBO COMPARATOR

identical capsule containing placebo (single dose) given preoperatively

Drug: Placebo

Interventions

Nabilone DRUG

Nabilone (0.5 mg) or placebo given preoperatively

Also known as: Cesamet

Cesamet (nabilone)

Placebo DRUG

Placebo Comparator: identical capsule containing placebo (single dose) given preoperatively

Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 or older with an American Society of Anesthesiologists (ASA) physical status of I to III who are scheduled to undergo elective surgery under general anesthesia with pre-anesthesia consultation prior to surgery.
• Subjects must be able to swallow study medication;
• At a risk of postoperative nausea and vomiting of at least 61% percent, according to a simplified risk score, based on the presence of at least three of the following risk factors: female sex, nonsmoker status, anticipated use of postoperative opioid and previous PONV or motion sickness.

You may not qualify if:

• Subjects with clinically significant or unstable cardiac, respiratory, hepatic, renal, or other major organ system disease
• Patients who will not be admitted to the PACU post-operatively (patients who are immediately transferred to the ICU)
• Known sensitivity to marijuana or other cannabinoid agents
• Psychotic illness or depression
• Addiction to illicit substances or alcohol
• Non-psychotic emotional disorders.
• Pregnant or lactating
• Subjects who suffer from chronic nausea and/or vomiting;
• Has had treatment with any other investigational drug within 12 weeks prior to randomization
• Subjects who, in the opinion of the investigator, would experience an unacceptable risk from administration of study drug

Sponsors & Collaborators

• Unity Health Toronto: lead

Study Sites (1)

St Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Related Publications (14)

• Habib AS, Gan TJ. Evidence-based management of postoperative nausea and vomiting: a review. Can J Anaesth. 2004 Apr;51(4):326-41. doi: 10.1007/BF03018236.

  PMID: 15064261 BACKGROUND

• Weinstein RS. Glucocorticoid-induced osteonecrosis. Endocrine. 2012 Apr;41(2):183-90. doi: 10.1007/s12020-011-9580-0. Epub 2011 Dec 15.

  PMID: 22169965 BACKGROUND

• Pertwee RG. Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists. Curr Med Chem. 2010;17(14):1360-81. doi: 10.2174/092986710790980050.

  PMID: 20166927 BACKGROUND

• Ware MA, Daeninck P, Maida V. A review of nabilone in the treatment of chemotherapy-induced nausea and vomiting. Ther Clin Risk Manag. 2008 Feb;4(1):99-107. doi: 10.2147/tcrm.s1132.

  PMID: 18728826 BACKGROUND

• Hsu ES. A review of granisetron, 5-hydroxytryptamine3 receptor antagonists, and other antiemetics. Am J Ther. 2010 Sep-Oct;17(5):476-86. doi: 10.1097/MJT.0b013e3181ea7821.

  PMID: 20844345 BACKGROUND

• Lewis IH, Campbell DN, Barrowcliffe MP. Effect of nabilone on nausea and vomiting after total abdominal hysterectomy. Br J Anaesth. 1994 Aug;73(2):244-6. doi: 10.1093/bja/73.2.244.

  PMID: 7917745 BACKGROUND

• Koivuranta M, Laara E, Snare L, Alahuhta S. A survey of postoperative nausea and vomiting. Anaesthesia. 1997 May;52(5):443-9. doi: 10.1111/j.1365-2044.1997.117-az0113.x.

  PMID: 9165963 BACKGROUND

• Gan TJ. Postoperative nausea and vomiting--can it be eliminated? JAMA. 2002 Mar 13;287(10):1233-6. doi: 10.1001/jama.287.10.1233. No abstract available.

  PMID: 11886298 BACKGROUND

• Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, Roewer N; IMPACT Investigators. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004 Jun 10;350(24):2441-51. doi: 10.1056/NEJMoa032196.

  PMID: 15190136 BACKGROUND

• Bremner WG, Kumar CM. Delayed surgical emphysema, pneumomediastinum and bilateral pneumothoraces after postoperative vomiting. Br J Anaesth. 1993 Aug;71(2):296-7. doi: 10.1093/bja/71.2.296.

  PMID: 8123411 BACKGROUND

• Fortier J, Chung F, Su J. Unanticipated admission after ambulatory surgery--a prospective study. Can J Anaesth. 1998 Jul;45(7):612-9. doi: 10.1007/BF03012088.

  PMID: 9717590 BACKGROUND

• Macario A, Weinger M, Carney S, Kim A. Which clinical anesthesia outcomes are important to avoid? The perspective of patients. Anesth Analg. 1999 Sep;89(3):652-8. doi: 10.1097/00000539-199909000-00022.

  PMID: 10475299 BACKGROUND

• Product monograph, Nabilone (Nabilone), submission control no: 124406, Valeant Canada Limitée/Limited, March 17, 2009

  BACKGROUND

• Levin DN, Dulberg Z, Chan AW, Hare GM, Mazer CD, Hong A. A randomized-controlled trial of nabilone for the prevention of acute postoperative nausea and vomiting in elective surgery. Can J Anaesth. 2017 Apr;64(4):385-395. doi: 10.1007/s12630-017-0814-3. Epub 2017 Feb 3.

  PMID: 28160217 DERIVED

MeSH Terms

Conditions

Postoperative Nausea and Vomiting

Interventions

nabilone

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nausea; Signs and Symptoms, Digestive; Signs and Symptoms; Vomiting

Study Officials

• Aaron P Hong, MD, FRCPC

  St Michael's Hospital, University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2014
• First Posted: April 16, 2014
• Study Start: April 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: November 1, 2015
• Last Updated: December 3, 2015

Record last verified: 2015-11

Locations

CA (1)