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

Sponsor

University Hospital, Geneva (Other)

Overall Status

Terminated

CT.gov ID

NCT00403806

Collaborator

(none)

215

Enrollment

Location

Arms

33.9

Duration (Months)

6.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Postoperative Nausea and Vomiting Postoperative Pain	Drug: dexamethasone Drug: Dexamethasone Drug: dexamethasone Drug: Saline	Phase 4

Detailed Description

Primary objective: To investigate the dose-effect relationship of prophylactic single-dose dexamethasone for the prevention of PONV in children undergoing adeno-tonsillectomy.
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.
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.
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

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

215 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, 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

Study Start Date :

Feb 1, 2005

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Intravenous dexamethasone 0.05 mg per kg bodyweight	Drug: dexamethasone intravenous dexamethasone 0.05 mg per kg bodyweight Other Names: Mephamesone
Active Comparator: 2 Intravenous dexamethasone 0.15 mg per kg bodyweight	Drug: Dexamethasone Intravenous dexamethasone 0.15 mg per kg bodyweight Other Names: mephamesone
Active Comparator: 3 Intravenous dexamethasone 0.5 mg per kg bodyweight	Drug: dexamethasone Intravenous dexamethasone 0.5 mg per kg bodyweight Other Names: mephamesone
Placebo Comparator: 4 Intravenous saline	Drug: Saline Intravenous saline Other Names: mephamesone

Outcome Measures

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 [24 hours postoperatively]

Secondary Outcome Measures

Dose-effect relationship for the prevention of postoperative pain [24 hours postoperatively]
Oral intake [10 days]
Effect on general outcome [10 days]
Investigation of safety (drug-related harm) [10 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 16 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)