Intraoperative Methadone in Children Undergoing Surgery (METACEBO)

The Use of Intraoperative Methadone in Children Undergoing Open Urological Surgery: a Randomized, Double-blind Trial

A prospective double-blind, randomized controlled trial investigating the effect of a single-dose of intraoperative methadone on postoperative pain and opioid consumption in 96 children undergoing open urological surgery.

Study Overview

• Status: Terminated
• Conditions: Pain, Postoperative; Pain, Acute; Children, Only
• Intervention / Treatment: Other: Placebo; Drug: Methadone Hydrochloride

Detailed Description

Treatment of postoperative pain is a challenge in younger children undergoing outpatient surgery. After discharge parents must assess pain intensity and administer analgesics, including opioids, as per needed. It has been shown that parents often hesitate to administer analgesics. The result is unrelieved pain that negatively affects the whole family and increases the risk of unscheduled contacts with healthcare professionals.

In children, methadone has shown a half-life of 19,2 +/-13,6 hours. Regarding outpatient surgery, methadone is an opioid with unique pharmalogical properties that may be advantageous. A single-dose of this long acting opioid administered perioperatively could provide a stable analgesia and potentially reduce the need for shorter-acting opioids in the PACU and at home.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 4 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Children scheduled for open urological surgery at the Outpatient Clinic at Aarhus University Hospital.

Exclusion Criteria:

• Age =/> 5 years at the date of operation
• Born preterm (Before gestational age of 37 weeks)
• Congenital heart disease
• Previous scrotal surgery
• Laparoscopic operation
• American Society of Anaesthesiologists (ASA) physical status lll, IV or V
• Allergy to study drugs
• Preoperative daily use of opioids
• Parents with inability to provide informed consent
• Severe respiratory insufficiency
• Acute abdominal pain
• Severe kidney insufficiency
• Treatment with rifampicin

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; A 5 ml syringe with saline will be prepared and study drug will be administered as intravenous bolus dose (0.1 mg/kg). The study drug will be administered at induction of anesthesia.	Other: Placebo; Single dose, intravenous bolus. Administered as the experimental arm.; Other Names: Saline
Experimental: Methadone; A 5 ml syringe with 1 mg/ml of methadone will be prepared and study drug will be administered as intravenous bolus dose (0.1 mg/kg). The study drug will be administered at induction of anesthesia.	Drug: Methadone Hydrochloride; Single dose, intravenous bolus, 0,1 mg/kg administered at induction of anesthesia.; Other Names: Methadone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients consumption of analgesics in the PACU.	Within the first 3 hours from extubation (or until discharge from PACU, if discharged before 3 hours).	3 hours
Pain intensity (highest score)	FLACC-score - Face, Legs, Activity, Cry og Consolability, 0-10, where 10 is the highest pain score. Within the first 3 hours from extubation (or until discharge from PACU, if discharged before 3 hours)	3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Readiness to discharge	Time for readiness to discharge from PACU assessed by PACU nurse.	6 hours
Patients need of supplemental oxygen in PACU	Need of supplemental oxygen within the first 3 hours after extubation,(or until discharge from PACU, if discharged before 3 hours)	3 hours
Awakenings during the first night after discharge.	Parents will answer whether the child have been awake and whether they believe the awakening(s) where due to pain.	24 hours
Pain intensity the first postoperative day	Assessed by parents, 3 FLACC-scores - Face, Legs, Activity, Cry og Consolability, 0-10, where 10 is the highest pain score, during the first postoperative day.	48 hours
Analgesic consumption following discharge until evening on the first postoperative day	From discharge until 8 PM the first day following surgery. Collected by parents.	36 hours
Unscheduled parental contacts to the hospital	Parental contacts to hospital regarding pain and/or analgesics until 4 days following surgery.	4 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
FLACC-scores - Face, Legs, Activity, Cry og Consolability, 0-10, where 10 is the highest pain score, at home	Parental experience with assessment of the FLACC-score at home following discharge.	48 hours

Collaborators and Investigators

• Sponsor: University of Aarhus

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2020
• Primary Completion (Actual): January 30, 2024
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: December 11, 2020
• First Submitted That Met QC Criteria: December 17, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: placebo; analgesics; postoperative; methadone; opioids
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Methadone
• Other Study ID Numbers: 23956082; 2020-002945-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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