Effectiveness of Triple Therapy With Palonosetron for PON Prophylaxis

NCT02635828 | Completed Phase 4 Results

• 1 other identifier: 2008H0170
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Postoperative Nausea and Vomiting

Keywords

Palonosetron; Craniotomy; Nausea; Vomiting

Outcome Measures

Primary Outcomes (1)

• PONV Incidence

  The incidence of PONV

  24 hours after end of surgery

Secondary Outcomes (1)

• Incidence of Subjects Significant QTc Changes in the EKG

  24 and 120 hours/discharge after end of surgery

Study Arms (1)

Triple therapy PONV prophylaxis

EXPERIMENTAL

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; Drug: Dexamethasone 10 mg IV; Drug: Promethazine 25 mg IV

Interventions

Palonosetron 0.075 mg IV DRUG

At induction of anesthesia, palonosetron 0.075 mg IV was given as PONV prophylaxis.

Also known as: Aloxi

Triple therapy PONV prophylaxis

Dexamethasone 10 mg IV DRUG

At induction of anesthesia, dexamethasone 10 mg IV was given as PONV prophylaxis.

Also known as: Decadron

Triple therapy PONV prophylaxis

Promethazine 25 mg IV DRUG

At induction of anesthesia, promethazine 25 mg was given as PONV prophylaxis.

Also known as: Phenergan

Triple therapy PONV prophylaxis

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ohio State University: lead
• Eisai Inc.: collaborator

Related Publications (20)

• 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 RESULT

• Kovac AL. Prevention and treatment of postoperative nausea and vomiting. Drugs. 2000 Feb;59(2):213-43. doi: 10.2165/00003495-200059020-00005.

  PMID: 10730546 RESULT

• 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. doi: 10.1097/00000539-200008000-00023.

  PMID: 10910848 RESULT

• Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ, Eubanks S, Kovac A, Philip BK, Sessler DI, Temo J, Tramer 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. doi: 10.1213/01.ane.0000068580.00245.95.

  PMID: 12818945 RESULT

• Audibert G, Vial V. [Postoperative nausea and vomiting after neurosurgery (infratentorial and supratentorial surgery)]. Ann Fr Anesth Reanim. 2004 Apr;23(4):422-7. doi: 10.1016/j.annfar.2004.01.005. French.

  PMID: 15120791 RESULT

• Manninen PH, Raman SK, Boyle K, el-Beheiry H. Early postoperative complications following neurosurgical procedures. Can J Anaesth. 1999 Jan;46(1):7-14. doi: 10.1007/BF03012507.

  PMID: 10078396 RESULT

• Apfel CC, Laara 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. doi: 10.1097/00000542-199909000-00022.

  PMID: 10485781 RESULT

• Sanger GJ, Andrews PL. Treatment of nausea and vomiting: gaps in our knowledge. Auton Neurosci. 2006 Oct 30;129(1-2):3-16. doi: 10.1016/j.autneu.2006.07.009. Epub 2006 Aug 24.

  PMID: 16934536 RESULT

• Habib AS, Gan TJ. Combination therapy for postoperative nausea and vomiting - a more effective prophylaxis? Ambul Surg. 2001 Jul;9(2):59-71. doi: 10.1016/s0966-6532(01)00103-2.

  PMID: 11454483 RESULT

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

  PMID: 14620731 RESULT

• 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. doi: 10.1007/BF03018234.

  PMID: 15064259 RESULT

• 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. doi: 10.1016/s0952-8180(99)00103-8.

  PMID: 10624646 RESULT

• 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. doi: 10.1016/s0001-2092(06)60241-x.

  PMID: 16528908 RESULT

• Siddiqui MA, Scott LJ. Palonosetron. Drugs. 2004;64(10):1125-32; discussion 1133-4. doi: 10.2165/00003495-200464100-00006.

  PMID: 15139789 RESULT

• 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.

  PMID: 18633025 RESULT

• 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. doi: 10.1093/annonc/mdg417.

  PMID: 14504060 RESULT

• 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. doi: 10.1093/annonc/mdl137. Epub 2006 Jun 9.

  PMID: 16766588 RESULT

• 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.

  PMID: 18633022 RESULT

• 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.

  PMID: 18633021 RESULT

• 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.

  PMID: 26870733 DERIVED

MeSH Terms

Conditions

Postoperative Nausea and Vomiting; Nausea; Vomiting

Interventions

Palonosetron; Dexamethasone; Calcium Dobesilate; Promethazine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Propylamines; Amines; Phenothiazines; Heterocyclic Compounds, 3-Ring

Limitations and Caveats

Our study also presented certain limitations that should be mentioned. To begin with, the study was designed without a control group; therefore, we were not able to compare the results from this regimen.

Results Point of Contact

• Title: Director of Neuroanesthesia
• Organization: The Ohio State Universtiy Wexner Medical Center

sergio.bergese@osumc.edu

6142933559

Study Officials

• Alberto A Uribe, M.D.

  Ohio State University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 8, 2015
• First Posted: December 21, 2015
• Study Start: October 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: October 1, 2011
• Last Updated: May 5, 2017
• Results First Posted: May 5, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share