Methadone in Cystectomy Patients

Not Applicable

Completed

• Conditions: Pathologic Processes; Neurologic Manifestations; Pain, Postoperative; Pain; Postoperative Complications; Bladder Cancer; Signs and Symptoms; Neurologic Symptoms; Side Effect of Drug
• Interventions: Drug: Methadone; Drug: Morphine

• Registration Number: NCT04475029
• Lead Sponsor: University of Aarhus

Brief Summary

The role of a single-dose intraoperative methadone on postoperative pain and opioid consumption in patients undergoing Surgeon Accuracy Robot Assistant cystectomy. A prospective double-blind, randomized controlled trial investigating the effect of a single-dose of intraoperative methadone in patients undergoing robotassisted cystectomy.

Detailed Description

During early recovery after surgery, intravenous opioids are typically administered to control the pain, either as intermittent bolus administration by nursing staff or by a patient-controlled analgesia device. Unfortunately, repeated doses or boluses of shorter-acting opioids, such as morphine, oxycodone and fentanyl, result in fluctuating blood concentrations, with the inherent risk of only relatively brief periods of adequate pain relief. Moreover, the use of shorter-acting opioids increases the risk of opioid-associated side effects, such as sedation, nausea and vomiting. An alternative approach to the postoperative use of shorter-acting opioids is therefore called for.

In this respect, methadone is an opioid with unique pharmalogical properties that may be advantageous when applied intraoperatively. A single-dose of this long acting opioid could provide a stable analgesia and potentially reduce the need for shorter-acting opioids

Method:

110 patients will be included in an investigator-initiated, prospective, randomised, double-blind, controlled trial with two arms: intervention arm (methadone 0.15 mg/kg ideal body weight). Control arm (morphine 0.15 mg/kg ideal body weight). The study will be GCP-monitored, and is approved by the Danish Health and Medicines Authority (2020041652) and the Central Denmark Region Committees on Health Research Ethics (1-10-72-275-19).

Hypothesis We hypothesize that a single-dose of intravenous intraoperative methadone is efficient and safe for the treatment of postoperative pain after cystectomy.

Objectives The primary objective is to determine whether a single-dose of intravenous methadone reduces postoperative opioid consumption when compared to morphine. The secondary objectives are to compare the effect and safety of intravenous methadone and morphine on postoperative pain, side effects, patient satisfaction and length of stay.

Study Timeline

• Study Start: 2020-07-06
• Study First Submitted: 2020-07-09
• Study First Submitted QC: 2020-07-16
• Study First Posted: 2020-07-17
• Status Verified: 2023-04
• Primary Completion: 2023-08-15
• Study Completion: 2023-08-17
• Last Update Submitted: 2023-09-11
• Last Update Posted: 2023-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 114

Inclusion Criteria

• All patients (≥18 years) scheduled for elective robot assisted cystectomy.

Exclusion Criteria

• American Society of Anesthesiologists (ASA) physical status IV or V
• Prolonged QTc-interval assessed by electrocardiogram (> 440 milliseconds)
• Existing treatment with a high risk of QTc-interval prolongation
• Allergy to study drugs
• Preoperative daily use of opioids
• Inability to provide informed consent
• Severe respiratory insufficiency (oxygen treatment at home)
• Heart failure (ejection fraction < 30%)
• Acute abdominal pain
• Signs of severe liver dysfunction (cirrhosis, inflammation/hepatitis or liver malignancy)
• Severe kidney insufficiency (estimated Glomerular Filtration Rate < 30 ml/min)
• Treatment with rifampicin
• Phaeochromocytoma
• Treatment with MAO-inhibitor during the last 14 days
• Pregnancy
• Nursing mothers
• Intraoperative conversion to open surgery (secondary inclusion criterion)
• Epidural analgesia in relation to surgical procedure

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Methadone	Methadone	A 10 ml syringe with 2 mg/ml of methadone will be prepared and and study drug will be administered as intravenous bolus dose (0.15 mg/kg treatment weight (height (cm) - 100)). The study drug will be administered 1 hour prior to expected extubation.
Morphine	Morphine	A 10 ml syringe with 2 mg/ml of morphine will be prepared and and study drug will be administered as intravenous bolus dose (0.15 mg/kg treatment weight (height (cm) - 100)). The study drug will be administered 1 hour prior to expected extubation.

Primary Outcome Measures

Name	Time	Method
Opioid consumption (morphine mg equivalents)	24 hours	• Opioid consumption within the first 24 hours after extubation

Secondary Outcome Measures

Name	Time	Method
Pain intensity	within 24 hours	NRS (0-10) at rest and when coughing. Questionnaires answered by nurse.
Opioid consumption (morphine mg equivalents)	72 hours	• Opioid consumption within the first 72 hours after extubation
PONV	Within 24 hours	• Nausea and/or vomiting (PONV) on a 4-point Likert scale (none/mild/moderate/severe). Questionnaires answered by nurse.
Level of sedation	3 hours	Level of sedation (Ramsey Sedation Score) assessed by PACU nurse.
Adverse events	6 hours	Any adverse events registered.
Patient satisfaction from 0-10.	24 hours	Patient satisfaction with pain management (NRS 0-10) Questionnaires answered by nurse.
Discharge	6 days	• Time from arrival to discharge from PACU and hospital (hours and minutes)

Trial Locations

Locations (1)

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark