Dexamethasone and Postoperative Bleeding Following Tonsillectomy in Children

Study Overview
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Brief Summary
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Tonsillectomy is one of the most frequently performed surgical interventions in children. However, it is associated with a high incidence of PostOperative Nausea and Vomiting (PONV), severe pain and haemorrhage. There is strong evidence on the efficacy of Dexamethasone in reducing the incidence of PONV and pain after tonsillectomy, which led to consider this drug as a first line treatment in routine anaesthesia practice in such surgical setting. However, in the last decade, there have been arguments about the potential role of Dexamethasone in increasing the risk of postoperative bleeding in children and studies addressing the haemorrhage risk following administration of Dexamethasone for tonsillectomy are inconclusive.Thus, this study is aimed at providing evidence for the safety profile of Dexamethasone with regard to the risk of post-tonsillectomy bleeding in children when administered as a single intraoperative dose.

Detailed Description
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This double-blind (investigator-surgeon-patient blinded), randomized, placebo control, multicentre, international, pragmatic, non-inferiority trial is designed to to provide evidence of the Dexamethasone safety profile with regard to the risk of post-tonsillectomy bleeding in children when administered as a single intraoperative dose of 0.15mg/kg. The study is also aimed at characterizing whether the co-administration of non steroidal anti-inflammatory drugs for analgesia potentiates the risk of postoperative haemorrhage. Sample size estimation is based on the definition of a minimal clinically important difference between the 2 groups of treatment (dexamethasone or normal saline) to be equal to 2% (non-inferiority margin). Thus, 3'794 children in total will be included with 1'897 children in each treatment group. The follow-up will be performed by the parents via an Application for Android and Apple that has been developed specifically for this study.

Official Title
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Dexamethasone and Postoperative Bleeding Following Tonsillectomy in Children: Double-blind, Randomized, Placebo Control, Multi-centre, International, Pragmatic, Non-inferiority Trial

Conditions
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Pain, Postoperative, Tonsillar Bleeding, Postoperative Nausea and Vomiting

Intervention / Treatment
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* Drug: Dexamethasone
* Drug: Sodium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged from 2 to 13 years admitted for tonsillectomy/ tonsillotomy with or without adenoidectomy Parents or legal responsible person willing and capable to follow data collection by the application (Android and iPhone) developed for this study Exclusion Criteria: Children under Aspirin or any other anticoagulants with or without Congenital Heart Disease Children with any bleeding disorders (ex. Haemophilia, Von Willebrand Disease)

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind (investigator-surgeon-patient blinded), randomized, placebo control, multi-centre, international, pragmatic, Non-inferiority trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexamethasone<br>Single intraoperative administration of 0.15 mg/kg of Dexamethasone intravenously with a maximum dose of 5 mg | Drug: Dexamethasone<br>* Is usually commercialized as dexamethasone phosphate as solution for injection<br>|
| Placebo Comparator: Sodium chloride<br>Single intraoperative administration of Sodium Chloride (NaCl) 0.9% intravenously | Drug: Sodium chloride<br>* prepared in the same intravenous volume to mimic experimental arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reoperation for postoperative bleeding | bleeding requiring surgical revision | Up to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory complications | 7) Incidence of perioperative respiratory critical events: laryngospasm, bronchospasm, stridor, bronchial aspiration, hypoxia (Saturation in oxygen<90% for 2 minutes) | Intraoperative and up to 2 hours postoperative | 
| Pain scores | Assessment of pain scores at the hospital with the total score for the FLACC (Face, Legs, Activity, Cry, Consolability) scale for children less than 2 years of age and by the numeric pain rating scale above. Then at home, assessment by parents with the short version of the parents postoperative pain measurement. | Up to 7 days after surgery | 
| Postoperative nausea, vomiting and retching | 2) Number of postoperative nausea and vomiting (PONV) and retching: during the stay at hospital with a maximum of 24 hours post-extubation | 3 intervals: 0-2 hours, 2-6 hours and 6-24 hours postoperatively | 
| Morbidity | Any admission to high dependency unit or ICU, readmission for following reasons: Ear, Nose and Throat infection, dehydration, pulmonary infection, other pulmonary complications, seizure or bleeding not requiring reoperation | Up to 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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reintervention, children