METAMORF: Methadone in Cystectomy Patients

Sponsor

University of Aarhus (Other)

Overall Status

Recruiting

CT.gov ID

NCT04475029

Collaborator

(none)

110

Enrollment

Location

Arms

Anticipated Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pain, Postoperative Postoperative Complications Pathologic Processes Bladder Cancer Pain Signs and Symptoms Neurologic Manifestations Neurologic Symptoms Side Effect of Drug	Drug: Methadone Drug: Morphine	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized controlled trial.Randomized controlled trial.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Randomisation and study medication will be handled by the hospital pharmacy. All research team members, caregiving clinicians and enrolled patients will be blinded to the study allocation arms and the randomisation list will be concealed until all statistical analyses are made.

Primary Purpose:

Treatment

Official Title:

Clinical Effectiveness and Safety of Intraoperative Methadone in Patients

Actual Study Start Date :

Jul 1, 2020

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: 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.

Drug: Methadone

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

Active Comparator: 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.

Drug: Morphine

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

Outcome Measures

Primary Outcome Measures

Opioid consumption (morphine mg equivalents) [3 hours]
• Opioid consumption within the first 3 hours after extubation
Opioid consumption (morphine mg equivalents) [24 hours]
• Opioid consumption within the first 24 hours after extubation

Secondary Outcome Measures

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)

Other Outcome Measures

Pain intensity [32-72 hours]
• Pain intensity (NRS, 0-10) at rest and coughing, questionnaires answered by nurse.
PONV [32-72 hours]
• Nausea and/or vomiting (PONV) on a 4-point Likert scale (none/mild/moderate/severe). Questionnaires answered by nurse.
Gastrointestinal function [6-72 hours]
Gastrointestinal function (flatus, stools) and laxatives ordained.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 110 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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