Dexamethasone and Postoperative Bleeding Following Tonsillectomy in Children (Blueberry)

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

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.

Study Overview

• Status: Terminated
• Conditions: Pain, Postoperative; Postoperative Nausea and Vomiting; Tonsillar Bleeding
• Intervention / Treatment: Drug: Dexamethasone; Drug: Sodium chloride

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 523
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, QC H4A 3L5
      • Queen Elizabeth Hospital of Montreal, Mc Gill
• Switzerland
  • Geneva, Switzerland, 1205
    • Geneva Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 9 years (Child)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Walid HABRE
• Collaborators: University Hospital, Geneva

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2020
• Primary Completion (Actual): March 30, 2023
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: December 1, 2019
• First Submitted That Met QC Criteria: December 3, 2019
• First Posted (Actual): December 5, 2019

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: children; reintervention
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Nausea; Pain, Postoperative; Vomiting; Hemorrhage; Postoperative Nausea and Vomiting; Postoperative Hemorrhage; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: 2019-02268

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data for all primary and secondary outcome measures will be made available
• IPD Sharing Time Frame: Up to 2 years following study completion
• IPD Sharing Access Criteria: Data access requests from National coordinators or from local investigators will be examined by the steering committee and an agreement will be signed prior to Data access
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No