Postoperative Oral Methadone After Major Spine Surgery; Safety, Feasibility and Efficacy in Prevention of Progression to Chronic Opioid Usage at 3 Months

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the feasibility and safety of a clinical protocol based on the administration of intraoperative intravenous methadone followed by a short regimen of oral/IV (if the patient is not able to take oral) methadone following spine surgery and to evaluate if methadone decreases persistent opioid usage at 3 months in comparison to placebo.

Official Title
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Postoperative Oral Methadone After Major Spine Surgery; Safety, Feasibility and Efficacy in Prevention of Progression to Chronic Opioid Usage at 3 Months - A Pilot Trial.

Conditions
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Spine Surgery

Intervention / Treatment
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* Drug: Postoperative methadone
* Drug: Postoperative placebo
* Drug: Rescue Analgesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults undergoing multilevel complex lumbar and/or thoracic spine fusion surgery, including revision surgeries Exclusion Criteria: BMI greater than 40

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Postoperative methadone<br> | Drug: Postoperative methadone<br>* Participants will receive intraoperative methadone (0.2 mg/kg ideal body weight intravenously but not exceeding 20mg) followed by oral/IV methadone postoperatively according to the following scheme: A) Opioid naïve patients will receive 5mg twice daily dosage of methadone on postoperative days 1 and 2 followed by 5 mg daily on postoperative days 3, 4, and 5. B) Patients taking opioids preoperatively will continue to receive their regular opioids and additionally receive 5 mg twice a day of methadone on postoperative days 1 and 2, followed by 5 mg per day on days 3, 4 and 5.<br>Drug: Rescue Analgesia<br>* PACU analgesia for both groups will be the usual care regime of fentanyl or hydromorphone bolus as prescribed by the physician anesthesiologist doing the case. All patients receive IV intravenous patient-controlled analgesia and rescue opioids which is usual care for postoperative pain.<br>|
| Placebo Comparator: Postoperative placebo<br> | Drug: Postoperative placebo<br>* Participants will receive intraoperative methadone intravenously 0.2mg/kg followed by oral placebo postoperatively according to the following scheme: Opioid naïve patients and patients taking opioids preoperatively will receive placebo tablets twice daily on day 1 and day 2 and once daily day 3, 4 and 5. Patients taking preoperative opioids will be able to return to their baseline opioids immediately after surgery.<br>Drug: Rescue Analgesia<br>* PACU analgesia for both groups will be the usual care regime of fentanyl or hydromorphone bolus as prescribed by the physician anesthesiologist doing the case. All patients receive IV intravenous patient-controlled analgesia and rescue opioids which is usual care for postoperative pain.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of study design as assessed by the number of participants for which scheduled postoperative methadone versus placebo were able to be administered according to the scheme described |  | Day of discharge (about 6 days after surgery) | 
| Feasibility of study design as assessed by number of participants for which safety was able to be assessed (EKGs) |  | postop days 1 and 5 | 
| Feasibility of study design as assessed by the number of participants for which safety was able to be assessed (respiratory events) | ability to evaluate adverse respiratory events | Day of discharge (about 6 days after surgery) | 
| Feasibility of study design as assessed by the number of participants for which postop opioid usage could be surveyed at 3 months |  | 3 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants for which opioid usage was able to be collected |  | Day of discharge (about 6 days after surgery) | 
| Safety as assessed by the number of patients developing respiratory depression | Saturation of Oxygen(SPO2) less than 85%, Respiratory rate <5 for longer than 3 minutes, ( Khanna et) increased oxygen requirement related to opioid-induced respiratory depression, naloxone use. The SPO2 will be monitored continuously per usual care in post anesthesia care unit (PACU) and every 4 hours in the ward. | by fifth day of hospital stay | 
| Safety as assessed by the number of patients developing clinically significant corrected QT interval(QTc )prolongation | QTc interval >500ms or >25% increase from baseline; number of patients developing arrhythmias needed treatment | by fifth day of hospital stay | 
| Safety as assessed by the number of participants with hallucinations |  | by fifth day of hospital stay | 
| Safety as assessed by the number of participants with dizziness |  | by fifth day of hospital stay | 
| Safety as assessed by the number of participants with Antiemetic use |  | by fifth day of hospital stay | 
| Safety as assessed by the number of participants with occurrence of nausea |  | by fifth day of hospital stay | 
| Safety as assessed by the number of participants with occurrence of vomiting |  | by fifth day of hospital stay | 
| Safety as assessed by the number of participants with occurrence of Ileus or constipation |  | by fifth day of hospital stay | 
| Safety as assessed by the number of subjects with persistent opioid use | This is scored from 0(less than once a week) to 4(constantly, a higher number indicating more opioid use) | 3 months after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioids