Blueberry: Dexamethasone and Postoperative Bleeding Following Tonsillectomy in Children

Sponsor

Walid HABRE (Other)

Overall Status

Recruiting

CT.gov ID

NCT04188431

Collaborator

University Hospital, Geneva (Other)

3,794

Enrollment

Locations

Arms

Anticipated Duration (Months)

1897

Patients Per Site

54.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pain, Postoperative Tonsillar Bleeding Postoperative Nausea and Vomiting	Drug: Dexamethasone Drug: Sodium chloride	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

3794 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double-blind (investigator-surgeon-patient blinded), randomized, placebo control, multi-centre, international, pragmatic, Non-inferiority trial.Double-blind (investigator-surgeon-patient blinded), randomized, placebo control, multi-centre, international, pragmatic, Non-inferiority trial.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Patients are allocated by block randomisation using sealed envelope system. An external person dedicated by Sponsor is in charge to randomize groups of treatment allocation through a website-generated list and to conceal the lists. Each centre receives the sealed opaque envelopes which contain treatment allocation. The envelope will be opened just before surgery. A member of the team not involved in the anaesthesia care will open an envelope and prepare the tested medication according to the result of randomization (Dexamethasone or NaCl). The repartition ratio between the 2 arms is 1:1 with a block size of 10.

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Nov 1, 2020

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Reoperation for postoperative bleeding [Up to 30 days]
bleeding requiring surgical revision

Secondary Outcome Measures

Respiratory complications [Intraoperative and up to 2 hours postoperative]
7) Incidence of perioperative respiratory critical events: laryngospasm, bronchospasm, stridor, bronchial aspiration, hypoxia (Saturation in oxygen<90% for 2 minutes)
Pain scores [Up to 7 days after surgery]
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.
Postoperative nausea, vomiting and retching [3 intervals: 0-2 hours, 2-6 hours and 6-24 hours postoperatively]
2) Number of postoperative nausea and vomiting (PONV) and retching: during the stay at hospital with a maximum of 24 hours post-extubation
Morbidity [Up to 30 days]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 13 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)