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Methadone in Cystectomy Patients (METAMORF)

Primary Purpose

Pain, Postoperative, Postoperative Complications, Pathologic Processes

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Methadone
Morphine
Sponsored by
University of Aarhus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pain, Postoperative focused on measuring morphine, methadone, analgesics, opioids, effect of drugs

Eligibility Criteria

18 Years - 110 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Aarhus University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Methadone

Morphine

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
July 9, 2020
Last Updated
September 11, 2023
Sponsor
University of Aarhus
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1. Study Identification

Unique Protocol Identification Number
NCT04475029
Brief Title
Methadone in Cystectomy Patients
Acronym
METAMORF
Official Title
Clinical Effectiveness and Safety of Intraoperative Methadone in Patients
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
July 6, 2020 (Actual)
Primary Completion Date
August 15, 2023 (Actual)
Study Completion Date
August 17, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aarhus

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Postoperative, Postoperative Complications, Pathologic Processes, Bladder Cancer, Pain, Signs and Symptoms, Neurologic Manifestations, Neurologic Symptoms, Side Effect of Drug
Keywords
morphine, methadone, analgesics, opioids, effect of drugs

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Randomized controlled trial.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Randomization and medication will be handled by hospital pharmacy. Randomisation list will be concealed until all statistical analyses are made. plan for data analysis was decided upon at a meeting with a statistician on September 7th, 2023. The plan was made before A and B lists were obtained from the hospital pharmacy. This study will be undertaken as an equivalence trial with the application of intention to treat analysis. Missing data are assumed to be missing at random. Primary outcome will be analyzed paired or unpaired t-test for difference, depending on distribution. Analysis of secondary outcome NRS will be reported as median(interquartile range) and compared between groups at the various times using the Mann-Whitney U test. If normal distributed multilevel mixed effects linear regression will be carried out. Analysis of other secondary outcomes will be dichotomized and presented for 3 and 24 hours with X2 test.
Allocation
Randomized
Enrollment
114 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Methadone
Arm Type
Experimental
Arm Description
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.
Arm Title
Morphine
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Methadone
Intervention Description
One intravenous administration of methadone (0.15 mg/kg treatment weight (height(cm)-100)) one hour prior to expected extubation.
Intervention Type
Drug
Intervention Name(s)
Morphine
Intervention Description
One intravenous administration of morphine (0.15 mg/kg treatment weight (height(cm)-100)) one hour prior to expected extubation.
Primary Outcome Measure Information:
Title
Opioid consumption (morphine mg equivalents)
Description
• Opioid consumption within the first 3 hours after extubation
Time Frame
3 hours
Title
Opioid consumption (morphine mg equivalents)
Description
• Opioid consumption within the first 24 hours after extubation
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Pain intensity
Description
NRS (0-10) at rest and when coughing. Questionnaires answered by nurse.
Time Frame
within 24 hours
Title
Opioid consumption (morphine mg equivalents)
Description
• Opioid consumption within the first 72 hours after extubation
Time Frame
72 hours
Title
PONV
Description
• Nausea and/or vomiting (PONV) on a 4-point Likert scale (none/mild/moderate/severe). Questionnaires answered by nurse.
Time Frame
Within 24 hours
Title
Level of sedation
Description
Level of sedation (Ramsey Sedation Score) assessed by PACU nurse.
Time Frame
3 hours
Title
Adverse events
Description
Any adverse events registered.
Time Frame
6 hours
Title
Patient satisfaction from 0-10.
Description
Patient satisfaction with pain management (NRS 0-10) Questionnaires answered by nurse.
Time Frame
24 hours
Title
Discharge
Description
• Time from arrival to discharge from PACU and hospital (hours and minutes)
Time Frame
6 days
Other Pre-specified Outcome Measures:
Title
Pain intensity
Description
• Pain intensity (NRS, 0-10) at rest and coughing, questionnaires answered by nurse.
Time Frame
32-72 hours
Title
PONV
Description
• Nausea and/or vomiting (PONV) on a 4-point Likert scale (none/mild/moderate/severe). Questionnaires answered by nurse.
Time Frame
32-72 hours
Title
Gastrointestinal function
Description
Gastrointestinal function (flatus, stools) and laxatives ordained.
Time Frame
6-72 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
110 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No

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Methadone in Cystectomy Patients

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