Effectiveness of Triple Therapy With Palonosetron for PON Prophylaxis

Postoperative Nausea and Vomiting Clinical Trial

Official title:

Studying the Effectiveness of Triple Therapy With Palonosetron, Dexamethasone and Promethazine for Prevention of Post Operative Nausea and Vomiting in High Risk Patients Undergoing Neurological Surgery and General Anesthesia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02635828
• Other study ID #: 2008H0170
• Status: Completed
• Phase: Phase 4
• First received: December 8, 2015
• Last updated: December 16, 2015
• Start date: October 2009
• Est. completion date: October 2011

Study information

• Verified date: December 2015
• Source: Ohio State University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Postoperative nausea and vomiting (PONV) is a displeasing experience that distresses surgical patients during the first 24 hours after a surgical procedure. The incidence of postoperative nausea occurs in about 50%, the incidence of postoperative vomiting is about 30%, and in high-risk patients, the PONV rate could be as high as 80%. Therefore, the study design of this single arm, non-randomized, pilot study assessed the efficacy and safety profile of a triple therapy combination with palonosetron, dexamethasone and promethazine to prevent PONV in patients undergoing craniotomies under general anesthesia.

Description:

At induction of anesthesia, a triple therapy of palonosetron 0.075 mg IV, dexamethasone 10 mg IV and promethazine 25 mg IV was given as PONV prophylaxis. After surgery, subjects were transferred to the surgical intensive care unit (SICU) or post anesthesia care unit as clinically indicated. Ondansetron 4 mg IV was administered as primary rescue medication to subjects with PONV symptoms. PONV was assessed and collected every 24 hours for 5 days via direct interview and/or medical charts review.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: October 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Adult patients, 18 to 85 years of age, of any race or gender. With an American Society of Anesthesiologist (ASA) physical status of I to III who are scheduled to undergo neurological surgery requiring opening of the cranium and Dura matter under general anesthesia, at Ohio State University Medical Center and who consent in writing to participating in this study.

• Post operative hospitalization expected to last at least 72 hours.

• Subjects whose surgery is expected to require at least 1 hours of general anesthesia

• Subjects who have a negative serum or urine pregnancy test within 1 day of surgery or who have been surgically sterilized or are postmenopausal.

Exclusion Criteria:

• Subjects who are prisoners, pregnant, mentally ill, under the age of 18 or over the age of 85, ASA classification of V, alcohol or drug abusers.

• Subjects with known hypersensitivity to any 5-HT3 antagonist, to any agent that is part of the anesthesia regimen, or to other medications to be administered under this protocol.

• Subjects who are breastfeeding.

• Subjects who have had retching/vomiting or moderate to severe nausea in the 24 hours prior to anesthesia or suffer chronic nausea and/or vomiting

• Subjects who have been treated with any drug or other treatment with anti-emetic efficacy within the last 24 hours prior to the start of treatment.

• Subjects who have participated in a clinical trial of an investigational drug within 30 days prior to surgery.

• Subjects who are participating in any other clinical study

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Nausea
• Postoperative Nausea and Vomiting
• Vomiting

Intervention

Drug:
• Palonosetron 0.075 mg IV
At induction of anesthesia, palonosetron 0.075 mg IV was given as PONV prophylaxis.
• Dexamethasone 10 mg IV
At induction of anesthesia, dexamethasone 10 mg IV was given as PONV prophylaxis.
• Promethazine 25 mg IV
At induction of anesthesia, promethazine 25 mg was given as PONV prophylaxis.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Ohio State University	Eisai Inc.

References & Publications (19)

Aapro MS, Grunberg SM, Manikhas GM, Olivares G, Suarez T, Tjulandin SA, Bertoli LF, Yunus F, Morrica B, Lordick F, Macciocchi A. A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nause — View Citation

Apfel CC, Läärä E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology. 1999 Sep;91(3):693-700. — View Citation

Audibert G, Vial V. [Postoperative nausea and vomiting after neurosurgery (infratentorial and supratentorial surgery)]. Ann Fr Anesth Reanim. 2004 Apr;23(4):422-7. Review. French. — View Citation

Board T, Board R. The role of 5-HT3 receptor antagonists in preventing postoperative nausea and vomiting. AORN J. 2006 Jan;83(1):209-16, 219-20. Review. — View Citation

Candiotti KA, Kovac AL, Melson TI, Clerici G, Joo Gan T; Palonosetron 04-06 Study Group. A randomized, double-blind study to evaluate the efficacy and safety of three different doses of palonosetron versus placebo for preventing postoperative nausea and v — View Citation

Fabling JM, Gan TJ, El-Moalem HE, Warner DS, Borel CO. A randomized, double-blinded comparison of ondansetron, droperidol, and placebo for prevention of postoperative nausea and vomiting after supratentorial craniotomy. Anesth Analg. 2000 Aug;91(2):358-61 — View Citation

Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ, Eubanks S, Kovac A, Philip BK, Sessler DI, Temo J, Tramèr MR, Watcha M; Department of Anesthesiology, Duke University Medical Center. Consensus guidelines for managing postoperative nausea and vomiting. Anesth — View Citation

Gralla R, Lichinitser M, Van Der Vegt S, Sleeboom H, Mezger J, Peschel C, Tonini G, Labianca R, Macciocchi A, Aapro M. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a — View Citation

Habib AS, El-Moalem HE, Gan TJ. The efficacy of the 5-HT3 receptor antagonists combined with droperidol for PONV prophylaxis is similar to their combination with dexamethasone. A meta-analysis of randomized controlled trials. Can J Anaesth. 2004 Apr;51(4) — View Citation

Habib AS, Gan TJ. Combination therapy for postoperative nausea and vomiting - a more effective prophylaxis? Ambul Surg. 2001 Jul;9(2):59-71. — View Citation

Khalil S, Philbrook L, Rabb M, Wells L, Aves T, Villanueva G, Amhan M, Chuang AZ, Lemak NA. Ondansetron/promethazine combination or promethazine alone reduces nausea and vomiting after middle ear surgery. J Clin Anesth. 1999 Nov;11(7):596-600. — View Citation

Kovac AL, Eberhart L, Kotarski J, Clerici G, Apfel C; Palonosetron 04-07 Study Group. A randomized, double-blind study to evaluate the efficacy and safety of three different doses of palonosetron versus placebo in preventing postoperative nausea and vomit — View Citation

Kovac AL. Prevention and treatment of postoperative nausea and vomiting. Drugs. 2000 Feb;59(2):213-43. Review. — View Citation

Ku CM, Ong BC. Postoperative nausea and vomiting: a review of current literature. Singapore Med J. 2003 Jul;44(7):366-74. Review. — 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

Manninen PH, Raman SK, Boyle K, el-Beheiry H. Early postoperative complications following neurosurgical procedures. Can J Anaesth. 1999 Jan;46(1):7-14. — View Citation

Rojas C, Stathis M, Thomas AG, Massuda EB, Alt J, Zhang J, Rubenstein E, Sebastiani S, Cantoreggi S, Snyder SH, Slusher B. Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor. Anesth Analg. 2008 Aug;107(2):469-78. doi: 10.1213/ane. — View Citation

Sanger GJ, Andrews PL. Treatment of nausea and vomiting: gaps in our knowledge. Auton Neurosci. 2006 Oct 30;129(1-2):3-16. Epub 2006 Aug 24. Review. — View Citation

Siddiqui MA, Scott LJ. Palonosetron. Drugs. 2004;64(10):1125-32; discussion 1133-4. Review. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of subjects reporting postoperative nausea and/or vomiting	Subjects will be asked if they experienced nausea or vomiting durign the first 24 hours after surgery	24 hours after end of surgery	No
Secondary	Incidence of subjects significant QTc changes in the EKG	EKG will be taken at baseline (before surgery), 24 hours after the end of surgery and 120/discharge after the end of surgery	24 and 120 hours/discharge after end of surgery	Yes