Effectiveness of Triple Therapy With Palonosetron for PON Prophylaxis

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ClinicalTrials.gov Identifier: NCT02635828

Recruitment Status : Completed

First Posted : December 21, 2015

Results First Posted : May 5, 2017

Last Update Posted : May 5, 2017

Sponsor:

Collaborator:

Eisai Inc.

Information provided by (Responsible Party):

Sergio Bergese, Ohio State University

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Postoperative Nausea and Vomiting	Drug: Palonosetron 0.075 mg IV Drug: Dexamethasone 10 mg IV Drug: Promethazine 25 mg IV	Phase 4

Detailed 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	40 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Prevention
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
Study Start Date :	October 2009
Actual Primary Completion Date :	May 2011
Actual Study Completion Date :	October 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Nausea and Vomiting

Drug Information available for: Dexamethasone Promethazine hydrochloride Diphenhydramine Promethazine Diphenhydramine hydrochloride Dexamethasone sodium phosphate Dexamethasone acetate Diphenhydramine citrate Palonosetron

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Triple therapy PONV prophylaxis 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.	Drug: Palonosetron 0.075 mg IV At induction of anesthesia, palonosetron 0.075 mg IV was given as PONV prophylaxis. Other Name: Aloxi Drug: Dexamethasone 10 mg IV At induction of anesthesia, dexamethasone 10 mg IV was given as PONV prophylaxis. Other Name: Decadron Drug: Promethazine 25 mg IV At induction of anesthesia, promethazine 25 mg was given as PONV prophylaxis. Other Name: Phenergan

Outcome Measures

Primary Outcome Measures :

PONV Incidence [ Time Frame: 24 hours after end of surgery ]
The incidence of PONV

Secondary Outcome Measures :

Incidence of Subjects Significant QTc Changes in the EKG [ Time Frame: 24 and 120 hours/discharge after end of surgery ]
The incidence of significant QTc prolongation was measured by comparing baseline EKG, 24 hours and 120 hours after surgery

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 85 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02635828

Sponsors and Collaborators

Ohio State University

Eisai Inc.

Investigators

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Study Chair:	Alberto A Uribe, M.D.	The Ohio State University Wexner Medical Center

More Information

Publications of Results:

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.

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

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.

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 Analg. 2003 Jul;97(1):62-71, table of contents. Review.

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.

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

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.

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.

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

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

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):311-9.

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.

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.

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

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.0b013e318172fa74. Erratum in: Anesth Analg. 2008 Oct;107(4):1405. Massuda, Edward B [corrected to Massuda, Ed B]; Rubenstein, Ed [corrected to Rubenstein, Edward]..

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 double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol. 2003 Oct;14(10):1570-7.

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 nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol. 2006 Sep;17(9):1441-9. Epub 2006 Jun 9.

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 vomiting. Anesth Analg. 2008 Aug;107(2):445-51. doi: 10.1213/ane.0b013e31817b5ebb.

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 vomiting over a 72-hour period. Anesth Analg. 2008 Aug;107(2):439-44. doi: 10.1213/ane.0b013e31817abcd3.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bergese SD, Puente EG, Antor MA, Capo G, Yildiz VO, Uribe AA. The Effect of a Combination Treatment Using Palonosetron, Promethazine, and Dexamethasone on the Prophylaxis of Postoperative Nausea and Vomiting and QTc Interval Duration in Patients Undergoing Craniotomy under General Anesthesia: A Pilot Study. Front Med (Lausanne). 2016 Feb 2;3:1. doi: 10.3389/fmed.2016.00001. eCollection 2016.

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Responsible Party:	Sergio Bergese, Professor, Ohio State University
ClinicalTrials.gov Identifier:	NCT02635828
Other Study ID Numbers:	2008H0170
First Posted:	December 21, 2015 Key Record Dates
Results First Posted:	May 5, 2017
Last Update Posted:	May 5, 2017
Last Verified:	March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No
Plan Description:	IPD will not be shared with other researchers.

Keywords provided by Sergio Bergese, Ohio State University:


Palonosetron Craniotomy Nausea Vomiting

Additional relevant MeSH terms:

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Nausea Vomiting Postoperative Nausea and Vomiting Signs and Symptoms, Digestive Postoperative Complications Pathologic Processes Promethazine Diphenhydramine Dexamethasone Palonosetron Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs	Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Serotonin 5-HT3 Receptor Antagonists Serotonin Antagonists Serotonin Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Antipruritics Dermatologic Agents Histamine H1 Antagonists Histamine Antagonists

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