Methadone for Spinal Fusion Surgery.

NCT ID: NCT04764825

Last Updated: 2024-11-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-26
• Study Completion Date: 2024-07-01

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.

Conditions

Pain, Postoperative; Back Pain; Opioid Use; Methadone; Degenerative Spondylolisthesis; Stenosis, Spinal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Methadone, induction

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).

Group Type: EXPERIMENTAL

Methadone

Intervention Type: DRUG

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.

Methadone, end of surgery

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).

Group Type: EXPERIMENTAL

Methadone

Intervention Type: DRUG

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.

Morphine

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).

Group Type: ACTIVE_COMPARATOR

Morphine

Intervention Type: DRUG

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.

Interventions

Methadone

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

Morphine

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aarhus University Hospital

OTHER

Sponsor Role: collaborator

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Aarhus University Hospital

Aarhus, , Denmark

Countries

Denmark

Other Identifiers

2020-004826-47

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

89456049

Identifier Type: -

Identifier Source: org_study_id