Remifentanil Tapering and Post-adenotonsillectomy Pain in Children

NCT03994146 | Terminated Phase 4 DMC

• 1 other identifier: 2019-001677-81
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

Tonsillectomy is the commonest operation of childhood and results in considerable pain. Remifentanil is a potent, ultra short acting opioid with a long- established safety record in paediatric anaesthesia that is used to provide intraoperative analgesia. There is evidence from adult studies that remifentanil increases postoperative pain, although this may be ablated if propofol (rather than inhalational anaesthesia) is used or if the remifentanil is tapered rather than abruptly discontinued at the end of surgery. The analgesic effect of gradual withdrawal of remifentanil at the end of surgery has not been studied in children and may have significant clinical implications. The primary measure of efficacy will be the dose of fentanyl rescue analgesia in the peri-operative period (1 mcg.kg-1 bolus for \>20% increase in pulse, blood pressure or movement intraoperatively or a FLACC(Face, Legs, Arms, Cry, Consolablity) score of \>5 in recovery).

Conditions

Child, Only; Pain; Tonsillectomy; Remifentanil

Outcome Measures

Primary Outcomes (1)

• Intravenous fentanyl consumption in the perioperative period (mcg/kg).

  Intravenous fentanyl consumption in the perioperative period (mcg/kg).

  From the induction of anaesthesia until discharge from the day case surgical unit.4 hours.

Secondary Outcomes (2)

• Faces Legs Activity Cry Consolability (FLACC) pain scores at 20,40,60,90 and 120 minutes after the operation to give a Sum of Pain Intensity Differences (SPID).

  From cessation of anaesthesia until 120 minutes after the cessation of anaesthesia.

• Parents' Post Operative Pain Measure (PPOMP) on post operative days 1,3,7,10,14 and 28

  From the cessation of anaesthesia until the 28th day following discharge from the day case surgical unit.

Study Arms (2)

Remifentanil tapering / Placebo abrupt cessation

EXPERIMENTAL

Syringe one contains Remifentanil 2 mg in 40 ml NaCl 9 mg.ml-1 = 50 µg.ml-1 which will be infused at a rate of 0.9 µg.kg-1.min-1 and Syringe two contains 40 ml NaCl 9 mg.ml-1 at an identical infusion rate. According to randomisation syringe one will then be tapered towards the end of surgery and syringe two abruptly stopped.

Drug: Remifentanil; Drug: Sodium Chloride 9mg/mL

Placebo tapering / Remifentanil abrupt cessation.

PLACEBO COMPARATOR

Syringe one contains 40 ml NaCl 9 mg.ml-1 and Syringe two contains Remifentanil 2 mg in 40 ml NaCl 9 mg.ml-1 = 50 µg.ml-1 which will be infused at a rate of 0.9 µg.kg-1.min-1. According to randomization syringe one will be tapered towards the end of surgery and syringe two abruptly stopped.

Drug: Remifentanil; Drug: Sodium Chloride 9mg/mL

Interventions

Remifentanil DRUG

Syringe containing 40 ml of Remifentanil 50 µg/ml for intravenous administration. In order to maintain double blinding two identical syringes, prepared by pharmacy according to randomisation, will be simultaneously infused. One of the syringes will be abruptly stopped at the end of the operation whilst the other is tapered by stepwise decreases in infusion rate prior to the end of surgery.

Also known as: Ultiva

Placebo tapering / Remifentanil abrupt cessation.; Remifentanil tapering / Placebo abrupt cessation

Sodium Chloride 9mg/mL DRUG

Syringe containing 40 ml of Sodium Chloride 9 mg/ml for intravenous administration. In order to maintain double blinding two identical syringes, prepared by pharmacy according to randomisation, will be simultaneously infused. One of the syringes will be abruptly stopped at the end of the operation whilst the other is tapered by stepwise decreases in infusion rate prior to the end of surgery.

Also known as: Normal saline, Placebo

Placebo tapering / Remifentanil abrupt cessation.; Remifentanil tapering / Placebo abrupt cessation

Eligibility Criteria

• Age: 1 Year - 10 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• American Society Anaesthesiology I-II children 1 to 10 years
• Weight over 10.0 Kg
• Presenting for tonsillotomy / tonsillectomy or adenotonsillectomy at Akershus Universitetssykehus, Lørenskog and Lovisenberg Diakonale Hospital, Norway

You may not qualify if:

• Children who have had airway surgery previously.
• Children who have had any type of surgery in the previous 12 months.
• Children using chronic pain medication or who have used analgesia in the 24 hours preceding surgery.
• Children who are known to suffer from NSAID sensitive asthma.
• Children with a known allergy to propofol or remifentanil.
• Pre-existing cardiac, renal, liver dysfunction.
• Children or parents who are not fluent in Norwegian or English.
• Children in whom more than three attempts at intravenous cannulation are required or in those who request an inhalational induction or premedication

Sponsors & Collaborators

• University Hospital, Akershus: lead

Study Sites (2)

Akershsus Universitetssykehus

Lørenskog, Akershus, 1478, Norway

Location

Lovisenberg Diakonale Sykehus

Oslo, 0456, Norway

Location

MeSH Terms

Conditions

Pain

Interventions

Remifentanil; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propionates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Signe Søvik, MD. PhD

  University Hospital, Akershus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Two syringes will be simultaneously infused during the operation. One will contain normal saline solution and the other remifentanil solution. Prior to the end of the operation one of the syringes will have a step wise decrease in infusion rate whilst the other will be abruptly stopped at the end of surgery. The syringes will be prepared according to randomisation in the hospital pharmacy and the identity of each syringe will be masked from all those involved in the study. The syringe randomisation will be de-coded following completion of recruitment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Model Details: Double blind, randomised, placebo controlled trial.

Study Record Dates

• First Submitted: June 13, 2019
• First Posted: June 21, 2019
• Study Start: January 16, 2020
• Primary Completion: August 18, 2023
• Study Completion: August 18, 2023
• Last Updated: August 22, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The data will be available following completion of the study and analysis and publication by the investigating team. There is no plan to time limit access to the data following this.
• Access Criteria: On request and following consultation with the Regional Ethics Committee and the Data Protection Officer at the host institution.

Locations

NO (2)