Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Methadone for Spinal Fusion Surgery. (METASPINE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04764825
Recruitment Status : Recruiting
First Posted : February 21, 2021
Last Update Posted : February 25, 2021
Sponsor:
Information provided by (Responsible Party):
University of Aarhus ( Aarhus University Hospital )

Brief Summary:
A prospective double-blind, randomized controlled trial investigating the effect of a single-dose of intraoperative methadone in patients undergoing spinal fusion.

Condition or disease Intervention/treatment Phase
Pain, Postoperative Back Pain Opioid Use Methadone Degenerative Spondylolisthesis Stenosis, Spinal Drug: Methadone Drug: Morphine Phase 4

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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: Intraoperative Methadone for Postoperative Pain Management in Spinal Fusion Surgery: a Prospective, Double-blind, Randomised Controlled Trial
Estimated Study Start Date : February 26, 2021
Estimated Primary Completion Date : July 1, 2023
Estimated Study Completion Date : November 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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).

Drug: 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.


Experimental: 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).
Drug: 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.


Active Comparator: 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).
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.





Primary Outcome Measures :
  1. Opioid consumption (mean cumulative MME) [ Time Frame: 6 hours ]
    Opioid consumption within the first 6 hours after extubation

  2. Opioid consumption (mean cumulative MME) [ Time Frame: 24 hours ]
    Opioid consumption within the first 24 hours after extubation


Secondary Outcome Measures :
  1. Pain intensity (NRS, 0-10) at rest and coughing [ Time Frame: 1-72 hours ]
    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

  2. Patient satisfaction with pain management [ Time Frame: 24 hours ]
    Satisfaction with pain management, measured from 0-10, 24 hours following extubation

  3. Nausea and/or vomiting (PONV) [ Time Frame: 6 - 24 hours ]
    Nausea and/or vomiting (PONV) on a 4 point Likert scale (none/mild/moderate/severe) at 6 and 24 hours.

  4. Readiness to discharge [ Time Frame: 2-24 hours ]
    Time from arrival to readiness for discharge from PACU(hours and minutes),

  5. Level of sedation [ Time Frame: 1 hour ]
    Level of sedation at observation in the PACU (Ramsay Sedation Scale at 1 hour after extubation)

  6. Adverse events [ Time Frame: 1-24 hours ]

    Any adverse events in the PACU

    • Hypoventilation (respiratory rate < 10/minutes)
    • Hypoxemia (peripheral oxygen saturation < 94%)

  7. Given treatment according to patient and investigator [ Time Frame: 24 hours ]
    Patient and investigator are asked to asses which treatment they believe was given

  8. 3 months follow-up [ Time Frame: 3 months ]
    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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04764825


Contacts
Layout table for location contacts
Contact: Camilla G Uhrbrand, MD 0045 23956082 camgaa@rm.dk
Contact: Lone Nikolajsen, PhD, DMSc lone.nikolajsen@clin.au.dk

Locations
Layout table for location information
Denmark
Aarhus University Hospital Recruiting
Aarhus, Denmark, 8200
Contact: Camilla G Uhrbrand, MD    0045 23956082    camgaa@rm.dk   
Contact: Lone Nikolajsen, MD, PhD, DMSc       lone.nikolajsen@clin.au.dk   
Principal Investigator: Camilla G Uhrbrand, MD         
Sub-Investigator: Kristian Friesgaard, MD, PhD         
Sponsors and Collaborators
Aarhus University Hospital
Layout table for additonal information
Responsible Party: Aarhus University Hospital
ClinicalTrials.gov Identifier: NCT04764825    
Other Study ID Numbers: 89456049
2020-004826-47 ( EudraCT Number )
First Posted: February 21, 2021    Key Record Dates
Last Update Posted: February 25, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Aarhus ( Aarhus University Hospital ):
methadone
postoperative
pain
spinalfusion
Additional relevant MeSH terms:
Layout table for MeSH terms
Spondylolisthesis
Spinal Stenosis
Pain, Postoperative
Pain
Neurologic Manifestations
Postoperative Complications
Pathologic Processes
Spondylolysis
Spondylosis
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Morphine
Methadone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antitussive Agents
Respiratory System Agents