Study of Prevention of Postoperative Nausea and Vomiting Using Cesamet

Postoperative Nausea and Vomiting Clinical Trial

— Cesamet  

Official title:

A Randomized Controlled Trial of Cesamet(R) (Nabilone) for the Prevention of Postoperative Nausea and Vomiting in Elective Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02115529
• Other study ID #: 13-242
• Status: Completed
• Phase: Phase 2
• First received: March 3, 2014
• Last updated: December 1, 2015
• Start date: April 2014
• Est. completion date: November 2015

Study information

• Verified date: November 2015
• Source: St. Michael's Hospital, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Description:

See above

Recruitment information / eligibility

• Status: Completed
• Enrollment: 331
• Est. completion date: November 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Nausea
• Postoperative Nausea and Vomiting
• Vomiting

Intervention

Drug:
• Nabilone
Nabilone (0.5 mg) or placebo given preoperatively
• Placebo
Placebo Comparator: identical capsule containing placebo (single dose) given preoperatively

Locations

Country	Name	City	State
Canada	St Michael's Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
St. Michael's Hospital, Toronto

Country where clinical trial is conducted

Canada, 

References & Publications (13)

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. — View Citation

Bremner WG, Kumar CM. Delayed surgical emphysema, pneumomediastinum and bilateral pneumothoraces after postoperative vomiting. Br J Anaesth. 1993 Aug;71(2):296-7. — View Citation

Fortier J, Chung F, Su J. Unanticipated admission after ambulatory surgery--a prospective study. Can J Anaesth. 1998 Jul;45(7):612-9. — View Citation

Gan TJ. Postoperative nausea and vomiting--can it be eliminated? JAMA. 2002 Mar 13;287(10):1233-6. Review. — View Citation

Habib AS, Gan TJ. Evidence-based management of postoperative nausea and vomiting: a review. Can J Anaesth. 2004 Apr;51(4):326-41. Review. — View Citation

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. Review. — View Citation

Koivuranta M, Läärä E, Snåre L, Alahuhta S. A survey of postoperative nausea and vomiting. Anaesthesia. 1997 May;52(5):443-9. — View Citation

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. — View Citation

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. — View Citation

Pertwee RG. Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists. Curr Med Chem. 2010;17(14):1360-81. Review. — View Citation

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

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. — View Citation

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

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Standardized score of nausea and/or vomiting severity if PONV occurs.		Prior to discharge from postanesthesia care unit, an expected average of two hours	No
Other	Pain score during the immediate post-operative period.		Prior to discharge from postanesthesia care unit, an expected average of two hours	No
Other	Use of intraoperative and postoperative opioids		Prior to discharge from postanesthesia care unit, an expected average of two hours	No
Other	Rates of known side effects.	Nabilone side effects include: drowsiness, vertigo, psychological high, dry mouth, depression, blurred vision, sensation disturbance, anorexia, headache, euphoria, and hallucinations (based on patient self-reporting).	Prior to discharge from postanesthesia care unit, an expected average of two hours	No
Other	Time to discharge from the PACU.		Prior to discharge from postanesthesia care unit, an expected average of two hours	No
Other	Rates of admission due to PONV		Prior to discharge from postanesthesia care unit, an expected average of two hours	No
Other	Antiemetics given prophylactically by the anesthesiologist.		Until discharge from postanesthesia care unit, an expected average of two hours	No
Primary	Incidence of postoperative nausea and/or vomiting		Prior to discharge from postanesthesia care unit, an expected average of two hours	No
Secondary	Number of antiemetic rescue medications given postoperatively.		Prior to discharge from postanesthesia care unit, an expected average of two hours	No