Methadone in Cystectomy Patients

Pain Clinical Trial

— METAMORF  

Official title:

Clinical Effectiveness and Safety of Intraoperative Methadone in Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04475029
• Other study ID #: 004581
• Secondary ID: 2019-004581-18
• Status: Completed
• Phase: N/A
• Start date: July 6, 2020
• Est. completion date: August 17, 2023

Study information

• Verified date: April 2023
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: August 17, 2023
• Est. primary completion date: August 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 110 Years

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Drug-Related Side Effects and Adverse Reactions
• Neurologic Manifestations
• Neurologic Symptoms
• Pain
• Pain, Postoperative
• Pathologic Processes
• Postoperative Complications
• Side Effect of Drug
• Signs and Symptoms

Intervention

Drug:
• Methadone
One intravenous administration of methadone (0.15 mg/kg treatment weight (height(cm)-100)) one hour prior to expected extubation.
• Morphine
One intravenous administration of morphine (0.15 mg/kg treatment weight (height(cm)-100)) one hour prior to expected extubation.

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pain intensity	• Pain intensity (NRS, 0-10) at rest and coughing, questionnaires answered by nurse.	32-72 hours
Other	PONV	• Nausea and/or vomiting (PONV) on a 4-point Likert scale (none/mild/moderate/severe). Questionnaires answered by nurse.	32-72 hours
Other	Gastrointestinal function	Gastrointestinal function (flatus, stools) and laxatives ordained.	6-72 hours
Primary	Opioid consumption (morphine mg equivalents)	• Opioid consumption within the first 3 hours after extubation	3 hours
Primary	Opioid consumption (morphine mg equivalents)	• Opioid consumption within the first 24 hours after extubation	24 hours
Secondary	Pain intensity	NRS (0-10) at rest and when coughing. Questionnaires answered by nurse.	within 24 hours
Secondary	Opioid consumption (morphine mg equivalents)	• Opioid consumption within the first 72 hours after extubation	72 hours
Secondary	PONV	• Nausea and/or vomiting (PONV) on a 4-point Likert scale (none/mild/moderate/severe). Questionnaires answered by nurse.	Within 24 hours
Secondary	Level of sedation	Level of sedation (Ramsey Sedation Score) assessed by PACU nurse.	3 hours
Secondary	Adverse events	Any adverse events registered.	6 hours
Secondary	Patient satisfaction from 0-10.	Patient satisfaction with pain management (NRS 0-10) Questionnaires answered by nurse.	24 hours
Secondary	Discharge	• Time from arrival to discharge from PACU and hospital (hours and minutes)	6 days