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Methadone for Spinal Fusion Surgery. (METASPINE)

Primary Purpose

Pain, Postoperative, Back Pain, Opioid Use

Status
Recruiting
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Methadone
Morphine
Sponsored by
Aarhus University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pain, Postoperative focused on measuring methadone, postoperative, pain, spinalfusion

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

- All patients (≥18 years ≤85) scheduled for elective spinal fusion surgery are screened for inclusion.

Exclusion Criteria:

  • Allergy to study drugs
  • American Society of Anaesthesiologists (ASA) physical status IV or V
  • Prolonged QTc-interval assessed by electrocardiogram(> 440 milliseconds)
  • Inability to provide informed consent
  • Severe respiratory insufficiency(Oxygen treatment at home)
  • Known or clinical signs of heart failure (Ejection Fraction <30%)
  • Acute alcohol intoxication/delirium tremens
  • Known or clinical signs of increased intracranial pressure
  • Acute liver disease
  • Acute abdominal pain
  • Known or clinical signs of severe liver dysfunction (cirrhosis, inflammation/hepatitis or liver malignancies)
  • Known or clinical signs of severe kidney insufficiency(eGFR<30)
  • Pregnancy: women of childbearing potential will be tested with serum-HCG prior to surgery, unless the woman is using a birth control method that may be considered as highly effective (based on CTFG 'recommendations related to contraception and pregnancy testing in clinical trials'). Women of childbearing potential is defined as women between menarche and post-menopausal, unless permanently steril. Post-menopausal is defined as no menses for 12 months without alternative medical cause.
  • Breastfeeding mothers
  • Existing treatment with a high risk of QTc-interval prolongation
  • Existing treatment with opioids (at least the last 7days) exceeding 60 mg morphine equivalents daily
  • Planned postoperative treatment with epidural analgesics and/or ketamine infusion
  • Treatment with rifampicin
  • Spinal fusion surgery over >4vertebral levels
  • Spinal fusion surgery due to malignant disease

Sites / Locations

  • Aarhus University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Methadone, induction

Methadone, end of surgery

Morphine

Arm Description

Patients receive methadone 0.15-0.2 mg/kg ideal bodyweight 10 minutes prior to surgery start (Syringe A). 45 minutes before expected extubation patients will receive saline (syringe B).

Patients receive saline 10 minutes prior to surgery start (Syringe A). 45 minutes before expected extubation patients will receive methadone 0.15-0.2 mg/kg ideal bodyweight (syringe B).

Patients receive saline 10 minutes prior to surgery start (Syringe A). 45 minutes before expected extubation patients will receive morphine 0.15-0.2 mg/kg ideal bodyweight (syringe B).

Outcomes

Primary Outcome Measures

Opioid consumption (mean cumulative MME)
Opioid consumption within the first 6 hours after extubation
Opioid consumption (mean cumulative MME)
Opioid consumption within the first 24 hours after extubation

Secondary Outcome Measures

Pain intensity (NRS, 0-10) at rest and coughing
Pain intensity from 0-10 in the affected area at when patient is at rest and coughing at the hours: 1, 3, 6, 24, 48 and 72 after extubation
Patient satisfaction with pain management
Satisfaction with pain management, measured from 0-10, 24 hours following extubation
Nausea and/or vomiting (PONV)
Nausea and/or vomiting (PONV) on a 4 point Likert scale (none/mild/moderate/severe) at 6 and 24 hours.
Readiness to discharge
Time from arrival to readiness for discharge from PACU(hours and minutes),
Level of sedation
Level of sedation at observation in the PACU (Ramsay Sedation Scale at 1 hour after extubation)
Adverse events
Any adverse events in the PACU Hypoventilation (respiratory rate < 10/minutes) Hypoxemia (peripheral oxygen saturation < 94%)
Given treatment according to patient and investigator
Patient and investigator are asked to asses which treatment they believe was given
3 months follow-up
Pain (NRS 0-10 in the surgical area and legs (left and right), analgesic consumption (opioids MME and secondary analgesics) and quality ogf life (Eq5D)

Full Information

First Posted
February 18, 2021
Last Updated
April 17, 2023
Sponsor
Aarhus University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04764825
Brief Title
Methadone for Spinal Fusion Surgery.
Acronym
METASPINE
Official Title
Intraoperative Methadone for Postoperative Pain Management in Spinal Fusion Surgery: a Prospective, Double-blind, Randomised Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 26, 2021 (Actual)
Primary Completion Date
February 1, 2024 (Anticipated)
Study Completion Date
May 1, 2024 (Anticipated)

3. Sponsor/Collaborators

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

4. Oversight

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

5. Study Description

Brief Summary
A prospective double-blind, randomized controlled trial investigating the effect of a single-dose of intraoperative methadone in patients undergoing spinal fusion.
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 pharmacological 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: 150 patients will be included in an investigator-initiated, prospective, randomised, double-blind, controlled trial with three arms: intervention arm 1 (methadone administered at induction 0.15-0.2 mg/kg ideal body weight), Intervention arm 2 (methadone administered in the end of surgery 0.15-0.2 mg/kg ideal body weight), Control arm (morphine administered in the end of surgery 0.15-0.2 mg/kg ideal body weight). The study will be GCP-monitored, and is approved by the Danish Health and Medicines Authority (2020103115) and the Central Denmark Region Committees on Health Research Ethics (1-10-72-278-20). Objective The aim of this study is to investigate the effect of a single dose of intravenous intraoperative methadone on postoperative opioid consumption, pain and side effects in patients scheduled for spinal fusion surgery. A single dose of intravenous intraoperative morphine will be used as an active comparator. Hypothesis Intravenous perioperative methadone reduces opioid consumption (oral cumulative equivalent dose) by 50% during the first 24 postoperative hours compared to intravenous morphine(primary outcome). Methadone reduces opioid consumption the first 6 postoperative hours compared to intravenous morphine Methadone reduces pain in the affected areas at rest and during coughing(1-72 hours after extubation) compared to intravenous morphine Methadone increases patient satisfaction with pain management during the first 24 postoperative hours compared to intravenous morphine on a Numerical Rating Scale (NRS) from 0 to 10, where 0 is unsatisfied and 10 is satisfied The effects of methadone is attenuated when administered prior to surgical incision compared to administration in the end of surgery The frequency of opioid-related side effects is similar in the groups compared.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Postoperative, Back Pain, Opioid Use, Methadone, Degenerative Spondylolisthesis, Stenosis, Spinal
Keywords
methadone, postoperative, pain, spinalfusion

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Randomized controlled trial
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Methadone, induction
Arm Type
Experimental
Arm Description
Patients receive methadone 0.15-0.2 mg/kg ideal bodyweight 10 minutes prior to surgery start (Syringe A). 45 minutes before expected extubation patients will receive saline (syringe B).
Arm Title
Methadone, end of surgery
Arm Type
Experimental
Arm Description
Patients receive saline 10 minutes prior to surgery start (Syringe A). 45 minutes before expected extubation patients will receive methadone 0.15-0.2 mg/kg ideal bodyweight (syringe B).
Arm Title
Morphine
Arm Type
Active Comparator
Arm Description
Patients receive saline 10 minutes prior to surgery start (Syringe A). 45 minutes before expected extubation patients will receive morphine 0.15-0.2 mg/kg ideal bodyweight (syringe B).
Intervention Type
Drug
Intervention Name(s)
Methadone
Intervention Description
The dosage administered differ in regards to age and tolerance to opioids: 0.2 mg/kg: all patients <65 years of age and all patients tolerant to opioids (defined as treatment with opioids (at least the last 7days) exceeding 60 oral morphine milligram equivalents daily. 0.15 mg/kg: Opioid naive patients > 65 years of age.
Intervention Type
Drug
Intervention Name(s)
Morphine
Intervention Description
The dosage administered differ in regards to age and tolerance to opioids: 0.2 mg/kg: all patients <65 years of age and all patients tolerant to opioids (defined as treatment with opioids (at least the last 7days) exceeding 60 oral morphine milligram equivalents daily. 0.15 mg/kg: Opioid naive patients > 65 years of age.
Primary Outcome Measure Information:
Title
Opioid consumption (mean cumulative MME)
Description
Opioid consumption within the first 6 hours after extubation
Time Frame
6 hours
Title
Opioid consumption (mean cumulative MME)
Description
Opioid consumption within the first 24 hours after extubation
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Pain intensity (NRS, 0-10) at rest and coughing
Description
Pain intensity from 0-10 in the affected area at when patient is at rest and coughing at the hours: 1, 3, 6, 24, 48 and 72 after extubation
Time Frame
1-72 hours
Title
Patient satisfaction with pain management
Description
Satisfaction with pain management, measured from 0-10, 24 hours following extubation
Time Frame
24 hours
Title
Nausea and/or vomiting (PONV)
Description
Nausea and/or vomiting (PONV) on a 4 point Likert scale (none/mild/moderate/severe) at 6 and 24 hours.
Time Frame
6 - 24 hours
Title
Readiness to discharge
Description
Time from arrival to readiness for discharge from PACU(hours and minutes),
Time Frame
2-24 hours
Title
Level of sedation
Description
Level of sedation at observation in the PACU (Ramsay Sedation Scale at 1 hour after extubation)
Time Frame
1 hour
Title
Adverse events
Description
Any adverse events in the PACU Hypoventilation (respiratory rate < 10/minutes) Hypoxemia (peripheral oxygen saturation < 94%)
Time Frame
1-24 hours
Title
Given treatment according to patient and investigator
Description
Patient and investigator are asked to asses which treatment they believe was given
Time Frame
24 hours
Title
3 months follow-up
Description
Pain (NRS 0-10 in the surgical area and legs (left and right), analgesic consumption (opioids MME and secondary analgesics) and quality ogf life (Eq5D)
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - All patients (≥18 years ≤85) scheduled for elective spinal fusion surgery are screened for inclusion. Exclusion Criteria: Allergy to study drugs American Society of Anaesthesiologists (ASA) physical status IV or V Prolonged QTc-interval assessed by electrocardiogram(> 440 milliseconds) Inability to provide informed consent Severe respiratory insufficiency(Oxygen treatment at home) Known or clinical signs of heart failure (Ejection Fraction <30%) Acute alcohol intoxication/delirium tremens Known or clinical signs of increased intracranial pressure Acute liver disease Acute abdominal pain Known or clinical signs of severe liver dysfunction (cirrhosis, inflammation/hepatitis or liver malignancies) Known or clinical signs of severe kidney insufficiency(eGFR<30) Pregnancy: women of childbearing potential will be tested with serum-HCG prior to surgery, unless the woman is using a birth control method that may be considered as highly effective (based on CTFG 'recommendations related to contraception and pregnancy testing in clinical trials'). Women of childbearing potential is defined as women between menarche and post-menopausal, unless permanently steril. Post-menopausal is defined as no menses for 12 months without alternative medical cause. Breastfeeding mothers Existing treatment with a high risk of QTc-interval prolongation Existing treatment with opioids (at least the last 7days) exceeding 60 mg morphine equivalents daily Planned postoperative treatment with epidural analgesics and/or ketamine infusion Treatment with rifampicin Spinal fusion surgery over >4vertebral levels Spinal fusion surgery due to malignant disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Camilla G Uhrbrand, MD
Phone
0045 23956082
Email
camgaa@rm.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Lone Nikolajsen, PhD, DMSc
Email
lone.nikolajsen@clin.au.dk
Facility Information:
Facility Name
Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Camilla G Uhrbrand, MD
Phone
0045 23956082
Email
camgaa@rm.dk
First Name & Middle Initial & Last Name & Degree
Lone Nikolajsen, MD, PhD, DMSc
Email
lone.nikolajsen@clin.au.dk
First Name & Middle Initial & Last Name & Degree
Camilla G Uhrbrand, MD
First Name & Middle Initial & Last Name & Degree
Kristian Friesgaard, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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Methadone for Spinal Fusion Surgery.

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