Dexamethasone for Paediatric Adeno-tonsillectomy - A Dose-finding Study

This study has been terminated.
(drug-related harm)
Sponsor:
Information provided by:
University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT00403806
First received: November 24, 2006
Last updated: August 13, 2010
Last verified: January 2009
  Purpose

Adeno-tonsillectomy is a commonly performed surgical procedure in children. Main morbidities are postoperative pain, nausea and vomiting, and haemorrhage. Non-steroidal anti-inflammatory drugs (NSAIDs)widely used for paincontrol increase the risk of postoperative bleeding and reoperation. Dexamethasone is an powerful antiemetic and has shown analgesic efficacy. Antiemetic and analgesic dose-response has never been established.


Condition Intervention Phase
Postoperative Nausea and Vomiting
Postoperative Pain
Drug: dexamethasone
Drug: Dexamethasone
Drug: Saline
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Antiemetic and Analgesic Efficacy and Safety of Dexamethasone for Paediatric Adeno-tonsillectomy - A Randomised, Placebo-controlled, Double-blind, Dose-finding Study

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Investigation of the dose-effect relationship of prophylactic single-dose dexamethasone for the prevention of postoperative nausea and vomiting in children undergoing adeno-tonsillectomy [ Time Frame: 24 hours postoperatively ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Dose-effect relationship for the prevention of postoperative pain [ Time Frame: 24 hours postoperatively ] [ Designated as safety issue: No ]
  • Oral intake [ Time Frame: 10 days ] [ Designated as safety issue: No ]
  • Effect on general outcome [ Time Frame: 10 days ] [ Designated as safety issue: No ]
  • Investigation of safety (drug-related harm) [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]

Enrollment: 215
Study Start Date: February 2005
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Intravenous dexamethasone 0.05 mg per kg bodyweight
Drug: dexamethasone
intravenous dexamethasone 0.05 mg per kg bodyweight
Other Name: Mephamesone
Active Comparator: 2
Intravenous dexamethasone 0.15 mg per kg bodyweight
Drug: Dexamethasone
Intravenous dexamethasone 0.15 mg per kg bodyweight
Other Name: mephamesone
Active Comparator: 3
Intravenous dexamethasone 0.5 mg per kg bodyweight
Drug: dexamethasone
Intravenous dexamethasone 0.5 mg per kg bodyweight
Other Name: mephamesone
Placebo Comparator: 4
Intravenous saline
Drug: Saline
Intravenous saline
Other Name: mephamesone

  Hide Detailed Description

Detailed Description:
  1. Primary objective: To investigate the dose-effect relationship of prophylactic single-dose dexamethasone for the prevention of PONV in children undergoing adeno-tonsillectomy.
  2. Secondary objective:To investigate the dose-effect relationship of prophylactic single-dose dexamethasone for the prevention of postoperative pain and its effect on general outcome in children undergoing adeno-tonsillectomy. To investigate the safety of dexamethasone in children undergoing adeno-tonsillectomy.
  3. Study Population:Children, aged 3 to 16 years, scheduled for elective tonsillectomy with or without adenoidectomy, and with or without ear tubes will be included. Children will stay the first postoperative night at the hospital and will be discharged the day after surgery.
  4. Randomisation and blinding:Children will be randomised to one of four groups of equal size:

    Group 1: Placebo NaCL 0.9%,Group 2:Dexa 0.05 mg/kg, Group 3: Dexa 0.15 mg/kg, Group 4:Dexa 0.5 mg/kg

    Indistinguishable 20 ml ampoules will be prepared and randomised by the Hospital Pharmacy. Children will receive 0.5 ml/kg of the solution as an IV bolus after induction of anaesthesia. The maximum volume of dexamethasone injected will be limited to 20 ml (corresponding to a maximum dose of 20 mg in a child with ≥40 kg bodyweight).

    Standardized Anesthesia technique and surgical procedure

  5. Variables measured

5.1. Intraoperatively

  • Type of surgery
  • Surgical time
  • Dose of opioid

5.2. Postoperatively

Follow up will be during the hospital stay, through a telephone interview 48 hours after surgery, and through a surgical control (standard procedure) at about one week. Preoperatively, parents and children will be instructed in the evaluation of pain. Parents will be given a questionnaire to be filled in twice daily (morning and evening) after discharge of the child, and to bring it back to the routine postoperative surgical control at one week (or to send it back by post).

Endpoint PONV

  • Cumulative incidence of vomiting (including retching) during the first 6 postoperative hours.
  • Cumulative incidence of nausea during the first 6 postoperative hours. Nausea is only recorded if the child is able to express the sensation of nausea.
  • Cumulative incidence of vomiting (including retching) during the first 24 postoperative hours.
  • Cumulative incidence of nausea during the first 24 postoperative hours. Rescue medication for PONV is with ondansetron (Zofran) 50 µg/kg IV or droperidol 20 µg/kg IV. Rescue antiemesis will be recorded.

Endpoint pain intensity In hospitalised children, pain assessment will be with the revised Faces Pain Scale (FPS-r) [Hicks et al, 2001] and with the conventional 0-10 cm Visual Analogue Scale (VAS). The FPS-r was adapted from the Faces Pain Scale [Bieri et al, 1990] in order to make it possible to score on the widely accepted 0-10 point metric. It shows a close linear relationship with the visual analogue pain scale across the age range from 4 to 16 years. In the case that a younger child is not able to express adequately its pain with the FPS-r or with the VAS we will use the CHEOP Scale (Children of Eastern Ontario Pain Scale); this is a behavioural observation scale [McGrath et al,1985]. Pain will be evaluated at arriving in the PACU, 1-hourly during the PACU stay, 4-hourly on the ward, and twice daily after discharge (see questionnaire). Sleeping children will not be woken up.

Cumulative doses per day of paracetamol/codeine and of any other analgesic (NSAIDs, opioids) will be recorded.

Further endpoints

  • Quality of sleep during each the night until the surgical visit. Each morning, the care-giver (nurse, parent) will estimate the child's quality of sleep on a NRS ranging from 0=did not sleep at all to 10=excellent sleep.
  • First oral intake of fluid (including ice cream); hours after end of surgery.
  • First oral intake of solid food; hours after end of surgery.
  • At discharge: Overall "satisfaction" judged by the nurse on a NRS ranging from 0=not satisfied at all to 10=very much satisfied.
  • Degree of stress on the part of the parents due to the child's "illness". Rated by the parents on a daily basis on a NRS scale from 0=not stressed at all to 10=very much stressed.
  • At the surgical visit: Overall "satisfaction" judged by the parents on a NRS ranging from 0=not satisfied at all to 10=very much satisfied.

Adverse effects, safety

  • Any minor complication: definition: no need for readmission.
  • Any major complication: definition: does need readmission (for instance, readmission due to bleeding, re-operation due to bleeding).
  Eligibility

Ages Eligible for Study:   3 Years to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

  • Elective tonsillectomy with or without adenoidectomy with or without eartubes

Exclusion criteria:

  • ASA > II
  • Allergie to Dexamethasone
  • Recent therapy with steroids or immunotherapy
  • Mental retardation
  • Children experiencing nausea or vomiting or have taken antiemetic medication within 24 hours before surgery
  • Additional surgery
  • Enrolement in another investigational study
  • Chronic infection or diabetes
  • Recent vaccination (less than 1 month prior to surgery)
  • Recent varicella infection (less than 1 month prior to surgery)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00403806

Locations
Switzerland
University Hospital of Geneva, Anesthesia Department
Geneva, Canton of Geneva, Switzerland, 1211
Sponsors and Collaborators
University Hospital, Geneva
Investigators
Principal Investigator: Christoph A Czarnetzki, MD, MBA anesthesia department
Study Chair: Martin Tramer, MD, PhD anesthesia department
  More Information

Publications:
Responsible Party: Christoph Czarnetzki MD, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT00403806     History of Changes
Other Study ID Numbers: NAC 04-005, Swissmedic DR 3028
Study First Received: November 24, 2006
Last Updated: August 13, 2010
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Geneva:
Adenotonsillectomy
Pediatrics
Postoperative Nausea and Vomiting
Pain
Oral intake
Dexamethasone
Dose finding

Additional relevant MeSH terms:
Vomiting
Pain, Postoperative
Postoperative Nausea and Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Postoperative Complications
Pathologic Processes
Pain
Nausea
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014