Safety and Efficacy of Palonosetron IV to Prevent Postoperative Nausea and Vomiting in Pediatric Patients

A Multicenter, Double-blind, Double-dummy, Randomized, Parallel Group, Stratified Study to Evaluate the Efficacy and Safety of a Single IV Dose of Palonosetron Compared to a Single IV Dose of Ondansetron to Prevent Postoperative Nausea and Vomiting in Pediatric Patients.

The primary objective of this study is to evaluate the efficacy of a single palonosetron IV dose compared to a single ondansetron IV dose in the prevention of postoperative nausea and vomiting through 24 hours after surgery in children aged from neonates up to less than 17 years undergoing elective surgical procedures requiring general intravenous anesthesia. The secondary objective is to evaluate the safety and tolerability of IV palonosetron in pediatric patients.

Study Overview

• Status: Completed
• Conditions: Postoperative Nausea and Vomiting
• Intervention / Treatment: Drug: Placebo to Ondansetron; Drug: Placebo to Palonosetron; Drug: Palonosetron; Drug: Ondansetron

• Study Type: Interventional
• Enrollment (Actual): 670
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1431FWO
    • CEMIC, Otorhinolaryngology Department
  • Rio Cuarto, Argentina, X5800AEV
    • Istituto Medico Rio Cuarto
• Czech Republic
  • Brno, Czech Republic, 61300
    • University Hospital Brno - Children's Medical Centre
  • Hradec Kralove, Czech Republic, 500 05
    • University Hospital Hradec Kralove
  • Olomouc, Czech Republic, 775 20
    • University Hospital Olomouc
  • Plzen-Lochotin, Czech Republic, 30460
    • University Hospital Pilsen- Paediatric Clinic
  • Praha, Czech Republic, 15006
    • University Hospital Motol
  • Znojmo, Czech Republic, 669 02
    • Hospital Znojmo, State-Funded Organisation, Department of Pediatrics
• Hungary
  • Budapest, Hungary, 1083
    • Semmeleis University
  • Budapest, Hungary, 1097
    • St Istvan and St Laszlo Corporate Hospital; Paediatric Intensive Care Unit
  • Budapest, Hungary, 1125
    • The Municipal Council's St Janos Hospital and North Buda United Hospitals; Central Anaesthesiology and Intensive Care Unit
  • Dunaújváros, Hungary, 2400
    • St Panthaleon Hospital; Central Department of Anaesthesiology and Intensive Care Unit
  • Gyula, Hungary, 5700
    • Pandy Kalman County Hospital; Department of Central Anaesthesiology and Intensive Care Unit
• Poland
  • Gdansk, Poland, 80-803
    • Department of Pediatric Surgery and Urology of Medical University of Gdansk
  • Lodz, Poland, 91-738
    • Department of Pediatric Anesthesiology and Intensive Care
  • Lublin, Poland, 20-093
    • Department of Pediatric Anesthesiology and Intensive Care
  • Olsztyn, Poland, 10-561
    • Department of Intensive Care and Anesthesiology
  • Wroclaw, Poland, 50-369
    • Department of Pediatric Surgery
• Puerto Rico
  • San Juan, Puerto Rico, PR 00936
    • University Pediatric Hospital
• Russian Federation
  • Arkhangelsk, Russian Federation, 132002
    • State Healthcare Institution Arkhangelsk Regional Children's Hospital
  • Saint Petersburg, Russian Federation, 190013
    • Federal State Institution: St. Petersburg Research Institute of Ear, Throat, Nose and Speech under the MoH Care and Social Development of the Russian Federation
  • Saint Petersburg, Russian Federation, 191025
    • International Clinic MEDEM
  • St-Petersburg, Russian Federation, 194100
    • St. Petersburg State Pediatric Medical Academy
  • Yaroslavl, Russian Federation, 150042
    • Yaroslavl Region State Healthcare Institution
• Ukraine
  • Dnipropetrovsk, Ukraine, 49100
    • Dnipropetrovsk Regional Childrens Clinical Hospital
  • Donetsk, Ukraine, 83052
    • Regional Childrens Clinical Hospital
  • Ivano-Frankivsk, Ukraine, 76000
    • Ivano-Frankivsk Regional Childrens Clinical Hospital
  • Kharkiv, Ukraine, 61000
    • City Clinical Hospital n#30
  • Kyiv, Ukraine, 01133
    • Research and Development Center for Prophylactic and Clinical Medicine
  • Kyiv, Ukraine, 01135
    • National Specialized Childrens Hospital OKHMATDYT
  • Odesa, Ukraine, 65061
    • V.P. Filatov Institute of Eye Diseases and Tissue Therapy
  • Zaporizhia, Ukraine, 69000
    • Zaporizhia Regional Clinical Childrens Hospital
• United States
  • Alabama
    • Florence, Alabama, United States, 35630
      • Shoals Clinical Research Associates
    • Sheffield, Alabama, United States, 35660
      • Shoals Medical Research, LLC
  • District of Columbia
    • Washington DC, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Florida
    • Miami, Florida, United States, 33136
      • Bascom Palmer Eye Institute - University of Miami
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Louisiana State University Health Sciences Center
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • CRC of Jackson
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • The University of North Carolina Hospitals
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45255
      • Clinical Trial Developers
  • Texas
    • Grapevine, Texas, United States, 76051
      • Texas Orthopedic Specialist, P.A
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patient aged from full term neonate to less than 17 years.

• In-patient or out-patient scheduled to undergo one of the following procedures:

  • ear, nose and throat surgery (e.g., tonsillectomy, adenoidectomy, myringotomy),
  • eye surgery (e.g. strabismus, vitreoretinal, cataract surgery),
  • urological surgery (e.g. orchidopexy, varicocoele),
  • plastic reconstructive surgery (e.g. cleft lip/cleft palate, burn procedures involving the scalp),
  • hernia repair,
  • orthopedic surgery (e.g. foot and ankle deformities, arthroscopic surgeries, ACL surgery),.
  • cardiac surgery,
  • neurosurgery.
• Patient is scheduled to undergo surgery requiring general intravenous anesthesia
• Patient is scheduled to receive nitrous oxide during the maintenance phase of anesthesia
• Patient weighs at least 3.2 kg
• ASA physical status I, II or III
• Fertile patients (male or female) must use reliable contraceptive measures
• Female patients who have attained menarche must have a negative pregnancy test at the screening visit (Visit 1) and at study treatment visit (Visit 2)
• For patients with known hepatic impairment: in the Investigator's opinion, the impairment does not jeopardize the patient's safety during the study
• For patients with known renal impairment: in the Investigator's opinion, the impairment does not jeopardize the patient's safety during the study

Exclusion Criteria:

• Lactating females
• Patient aged ≤6 years who received any investigational drug within 90 days prior to Day 1, or patient aged >6 years who received any investigational drug within 30 days prior to Day 1 or is expected to receive investigational drugs prior to study completion.
• Patient having participated in any previous trial with palonosetron.
• History of allergy to any components or any other contraindications to the use of any 5-HT3 receptor antagonists
• Patient to undergo emergency surgery
• Patient scheduled to receive regional anesthesia (lumbar, epidural, spinal) alone or in conjunction with general intravenous anesthesia
• Patient scheduled to receive laryngeal mask anesthesia
• Patient scheduled to receive propofol during the maintenance phase of anesthesia
• Patient suffering from any concomitant disease uncontrolled by therapy, which, in the judgment of the Investigator, could compromise the outcome of surgery
• Patient with history of gastro-esophageal reflux (except for patients up to 12 months)
• Patient with ongoing vomiting from any organic cause
• Patient having experienced any vomiting, retching, or nausea within 24 hours prior to the administration of the study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Palonosetron and placebo to Ondansetron; Intervention: Drug: Palonosetron	Drug: Placebo to Ondansetron; Drug: Palonosetron; Single dose Palonosetron IV 1 mcg/kg (up to a maximum total dose of 0.075 mg)
Active Comparator: Ondansetron and placebo to Palonosetron; Intervention: Drug: Comparator: Ondansetron	Drug: Placebo to Palonosetron; Drug: Ondansetron; Single dose Ondansetron IV: 0 months to 12 years dose: 0.1 mg/kg for ≤ 40 kg and 4 mg for >40 kg;; 13 years to less than 17 years dose: 4 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With Complete Response	Complete Response was defined as no vomiting, no retching, and no use of antiemetic rescue medication during the first 24 hours postoperatively, starting at T0. Time 0 (T0) was defined as the time when the patient wakes up and is able to show any active reaction postoperatively.	0-24 hours after T0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With no Vomiting	Time 0 (T0) was defined as the time when the patient wakes up and is able to show any active reaction postoperatively.	0-24 hours after T0
Proportion of Patients Without Emetic Episodes	An emetic episode was defined as one or more continuous vomits (expulsion of stomach contents through the mouth) or retches (an attempt to vomit that is not productive of stomach contents). Time 0 (T0) was defined as the time when the patient wakes up and is able to show any active reaction postoperatively.	0-24 hours after T0
Proportion of Patients Without Antiemetic Rescue Medication	Rescue medications are any medications with potential antiemetic effect taken in the 24 hours after patient wake-up from anaesthesia (T0).Time 0 (T0) was defined as the time when the patient wakes up and is able to show any active reaction postoperatively.	0-24 hours after T0
Proportion of Patients Without Nausea (Patient Aged > 6 Years)		0-24 hours after T0

Collaborators and Investigators

• Sponsor: Helsinn Healthcare SA

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: July 14, 2011
• First Submitted That Met QC Criteria: July 15, 2011
• First Posted (Estimate): July 18, 2011

Study Record Updates

• Last Update Posted (Estimate): July 30, 2014
• Last Update Submitted That Met QC Criteria: July 29, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Pediatric; Ondansetron; Palonosetron; Prevention of Postoperative Nausea and Vomiting
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Signs and Symptoms, Digestive; Nausea; Vomiting; Postoperative Nausea and Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin 5-HT3 Receptor Antagonists; Antipruritics; Palonosetron; Ondansetron
• Other Study ID Numbers: PALO-10-14