Pain, PostoperativePhase 4METASPINENCT04764825
Methadone for Spinal Fusion Surgery.
A Phase 4 study testing Methadone and Morphine in people with Pain, Postoperative and Back Pain, run by University of Aarhus at 1 site in Denmark.
Trial summary
A prospective double-blind, randomized controlled trial investigating the effect of a single-dose of intraoperative methadone in patients undergoing spinal fusion. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Pain, Postoperative, Back Pain, Opioid Use
- What is being tested?
- Methadone and Morphine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 1 siteDenmark
- Study dates
- 26 Feb 2021to 1 Jul 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients (≥18 years ≤85) scheduled for elective spinal fusion surgery are screened for inclusion.
Who cannot join
- 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%)
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Intraoperative Methadone for Postoperative Pain Management in Spinal Fusion Surgery: a Prospective, Double-blind, Randomised Controlled Trial
A prospective double-blind, randomized controlled trial investigating the effect of a single-dose of intraoperative methadone in patients undergoing spinal fusion.
Read the 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
- Being tested
- Methadone, Morphine
- Keywords
- methadone, postoperative, pain, spinalfusion
- Medical subject headings
- Pain, Postoperative, Back Pain, Spinal Stenosis, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethadoneDrug
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.
MorphineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Methadone, induction | Experimental | 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). Receives: Drug: Methadone |
| Methadone, end of surgery | Experimental | 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). Receives: Drug: Methadone |
| Morphine | Active comparator | 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). Receives: Drug: Morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Opioid consumption (mean cumulative MME)
Opioid consumption within the first 6 hours after extubation
Measured: 6 hours
Opioid consumption (mean cumulative MME)
Opioid consumption within the first 24 hours after extubation
Measured: 24 hours
Secondary outcomes (8)
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
Measured: 1-72 hours
Patient satisfaction with pain management
Satisfaction with pain management, measured from 0-10, 24 hours following extubation
Measured: 24 hours
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.
Measured: 6 - 24 hours
Readiness to discharge
Time from arrival to readiness for discharge from PACU(hours and minutes),
Measured: 2-24 hours
Level of sedation
Level of sedation at observation in the PACU (Ramsay Sedation Scale at 1 hour after extubation)
Measured: 1 hour
Adverse events
Any adverse events in the PACU
- Hypoventilation (respiratory rate < 10/minutes)
- Hypoxemia (peripheral oxygen saturation < 94%)
Measured: 1-24 hours
Given treatment according to patient and investigator
Patient and investigator are asked to asses which treatment they believe was given
Measured: 24 hours
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)
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start26 Feb 2021
- Primary completion19 Mar 2024
- Study completion1 Jul 2024
Why it stopped: Due to extremely slow inclusion rates.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pain, PostoperativeStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04764825
- Sponsor's protocol ID
- 89456049
- Other IDs
- 2020-004826-47
- Acronym
- METASPINE
- Status last verified
- Apr 2023
- First submitted
- 18 Feb 2021
- Last updated
- 25 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intraoperative Methadone for Postoperative Pain Management in Spinal Fusion Surgery: a Prospective, Double-blind, Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT04764825
- Acronym / sponsor ID
- METASPINE / 89456049
- Conditions
- Pain, Postoperative, Back Pain, Opioid Use, Methadone, Degenerative Spondylolisthesis, Stenosis, Spinal
- Keywords
- methadone, postoperative, pain, spinalfusion
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to extremely slow inclusion rates.
- Enrolment
- 114 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Aarhus University Hospital
- Study start
- 26 Feb 2021 (actual)
- Primary completion
- 19 Mar 2024 (actual)
- Study completion
- 1 Jul 2024 (actual)
- First posted
- 21 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Methadone, induction | Experimental | Drug: MethadonePatients 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). |
| Methadone, end of surgery | Experimental | Drug: MethadonePatients 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). |
| Morphine | Active comparator | Drug: MorphinePatients 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). |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All patients (≥18 years ≤85) scheduled for elective spinal fusion surgery are screened for inclusion.
Key exclusion criteria (20 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethadoneThe 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. | Drug | Methadone, end of surgery, Methadone, induction |
| MorphineThe 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. | Drug | Morphine |
Primary outcome
Opioid consumption (mean cumulative MME)
Time frame: 6 hours
Opioid consumption within the first 6 hours after extubation
Opioid consumption (mean cumulative MME)
Time frame: 24 hours
Opioid consumption within the first 24 hours after extubation
8 secondary outcomes
Pain intensity (NRS, 0-10) at rest and coughing
Time frame: 1-72 hours
Patient satisfaction with pain management
Time frame: 24 hours
Nausea and/or vomiting (PONV)
Time frame: 6 - 24 hours
Readiness to discharge
Time frame: 2-24 hours
Level of sedation
Time frame: 1 hour
Adverse events
Time frame: 1-24 hours
Given treatment according to patient and investigator
Time frame: 24 hours
3 months follow-up
Time frame: 3 months
Results and safety
The study was stopped early (reason given: Due to extremely slow inclusion rates.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methadone and Morphine in people with Pain, Postoperative and Back Pain, run by University of Aarhus at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Due to extremely slow inclusion rates.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Opioid consumption (mean cumulative MME) (time frame: 6 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2024.