Intravenous Methadone in Perioperative Acute and Chronic Management in Chinese Adult Cardiac Surgical Patients

NCT05913284 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 2022.636-T
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

Despite modern day improvements in pain treatment and availability of different analgesic modalities, suboptimal postoperative pain control remains an issue in cardiac surgical patients. Poorly controlled acute postoperative pain is associated with adverse physiological outcomes that impair the recovery of cardiac surgical patients. It is associated with decreased patient satisfaction, delayed postoperative ambulation, and the development of chronic postsurgical pain (CPSP). Intravenous opioids such as fentanyl and morphine have been the mainstay of perioperative analgesia for cardiac surgery, either by intermittent boluses by healthcare staff or through a patient-controlled device (PCA). The primary problem with this mechanism of delivery is that significant fluctuations in serum opioid concentrations can occur, resulting in effects which range from inadequate analgesia to overdose and respiratory depression. In contrast to intermittent administration of short-acting opioids such as morphine and fentanyl, a single dose administration of methadone can be considered.

Conditions

Pain, Postoperative; Pain, Acute; Pain, Chronic; Anesthesia

Keywords

cardiac surgery

Outcome Measures

Primary Outcomes (4)

• Proportion of patients that can be recruited

  defined as the number of patients that fit the recruitment criteria divided by the total number of elective cardiac surgical patients over a period of time

  At recruitment

• Proportion of patients excluded based on inclusion and exclusion criteria

  Number of patients excluded divided by the total number of elective cardiac surgical patients over a period of time

  At recruitment

• Cardiac arrhythmia from side effects of methadone

  New-onset cardiac arrhythmia or prolonged QTc attributed to methadone

  intraoperatively

• Cardiac arrhythmia from side effects of methadone

  New-onset cardiac arrhythmia or prolonged QTc attributed to methadone

  Within 72 hours postoperatively

Secondary Outcomes (15)

• Ventilator time

  Within 24 postoperatively in ICU

• Total morphine consumption

  intraop and postop within 24 hours

• Intraoperative fentanyl consumption

  intraoperative

• Pain score at rest

  Within 72 hours postop

• Pain score on exertion

  within 72 hours postop

Study Arms (2)

Methadone group

EXPERIMENTAL

Upon induction of anaesthesia, intravenous methadone 0.2mg/kg (maximum dose 20mg) in blind labelling will be administered by infusion over 30 minutes. No further morphine will be given throughout the operation, but administration of Intraoperative fentanyl will be left to the discretion of the attending anaesthesiologists

Drug: Methadone

Morphine group

ACTIVE COMPARATOR

Upon induction of anaesthesia, intravenous morphine that is of equipotent dose as 0.2mg/kg methadone or 20mg methadone if maximum dose of interventional drug is reached) in blind labelling will be administered by infusion over 30 minutes. No further morphine will be given throughout the operation, but administration of Intraoperative fentanyl will be left to the discretion of the attending anaesthesiologists

Drug: Morphine

Interventions

Methadone DRUG

The drug will be prepared by study investigator and then handover to the anaesthesiologist which is blinded to the study. The syringe will be labelled as study drug and given on induction of anaesthesia as intravenous infusion over 30 minutes

Methadone group

Morphine DRUG

The drug will be prepared by study investigator and then handover to the anaesthesiologist which is blinded to the study. The syringe will be labelled as study drug and given on induction of anaesthesia as intravenous infusion over 30 minutes

Morphine group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 or older
• Elective primary isolated coronary artery bypass grafting, aortic valve repair/replacement, mitral valve repair/replacement or combined coronary artery bypass/valve procedure via sternotomy
• Expected extubation within 12 hours of surgery

You may not qualify if:

• emergency surgery
• aortic surgery
• redo surgery
• preoperative renal failure requiring renal replacement therapy or creatinine clearance \<30ml/min (calculated by Cockcroft-Gault Formula
• liver dysfunction (liver enzymes twice upper limit normal)
• LVEF \< 40% at baseline
• mechanical circulatory support in perioperative period
• history of chronic pain or who regularly used pain medications (except paracetamol and non-steroidal anti-inflammatory drugs)
• history of psychiatric illnesses or illicit drug use
• intraoperative use of remifentanil
• unable to provide informed consent

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Related Publications (1)

• Wong HMK, Wong WT, Liu X, Au SSW, Wong RHL. Intravenous methadone for perioperative acute and chronic pain management in Chinese adult cardiac surgical patients: A protocol for pilot randomized controlled trial. PLoS One. 2025 Jun 2;20(6):e0323820. doi: 10.1371/journal.pone.0323820. eCollection 2025.

  PMID: 40455731 DERIVED

MeSH Terms

Conditions

Pain, Postoperative; Acute Pain; Chronic Pain

Interventions

Methadone; Morphine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Man Kin WONG, MBChB

  Chinese Unversity of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: The study syringes containing the drug solution will be of identical appearance and with blind labelling so that the primary care team and the patient will be blinded to the treatments. An independent assessor blinded to the study will be responsible for the data analysis
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The patients are randomized to receive either methadone 0.2mg/kg (maximum dose of 20mg) or equipotent dose of morphine, added to a syringe containing saline made up to 50ml in total. Randomization will be carried out by an independent investigator, on the day before operation, from pre-prepared envelops each containing the group assignment of either methadone or morphine group. The group assignment will be done by sequence generation with computer models.

Study Record Dates

• First Submitted: May 26, 2023
• First Posted: June 22, 2023
• Study Start: January 15, 2024
• Primary Completion: February 1, 2026
• Study Completion: April 1, 2026
• Last Updated: March 27, 2025

Record last verified: 2025-03

Locations

HK (1)