The Effect of Chlorzoxazone on Moderate to Severe Postoperative Pain After Spine Surgery

Study Overview
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Brief Summary
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Chlorzoxazone is a centrally acting muscle relaxant used to treat muscle spasm and the resulting pain or discomfort. It acts on the spinal cord by depressing reflexes. Our purpose is to investigate the effect of chlorzoxazone on moderate to severe postoperative pain after spine surgery. Our hypothesis is that chlorzoxazone can reduce postoperative pain and reduce opioidconsumption and side effects compared to placebo.

Official Title
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The Effect of Chlorzoxazone on Moderate to Severe Postoperative Pain After Spine Surgery

Conditions
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Chlorzoxazone, Postoperative Pain

Intervention / Treatment
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* Drug: Placebo
* Drug: Chlorzoxazone
* Drug: Morphine
* Drug: Zofran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing spine surgery in general anaesthesia. Postoperative pain > 50 mm on the VAS scale during mobilization. Patients who have not received analgesia 1 hour prior to inclusion. ASA 1-3. BMI > 18 og < 40. Fertile women need a negative HCG urine test. Patients who have given their written consent to participate and understand the contents of the protocol. Exclusion Criteria: Participation in another clinical trial. Patients who do not speak and/or understand Danish. Fertile women with a positive HCG urine test. Allergy to the drugs used in the trial. Alcohol or medicine abuse, assessed by investigator. Daily use of strong opioids (morphine, ketobemidone, oxynorm, methadone, fentanyl) Daily chlorzoxazone treatment. Known or suspected porphyria.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chlorzoxazone<br>Oral administration of chlorzoxazone 500 mg (two 250 mg tablets) Morphine. Patient controlled intravenous morphine (PCA-pump), bolus 2.5 mg, lock-out-time 10 minutes. Concentration : Morphin 1 mg/ml. Zofran 4 mg iv in case of moderate to severe nausea, supplemented by Zofran 1 mg iv if needed | Drug: Chlorzoxazone<br>* Two 250 mg chlorzoxazone tablets<br>Drug: Morphine<br>* Patient controlled intravenous morphine (PCA-pump), bolus 2.5 mg, lock-out-time 10 minutes. Concentration : Morphin 1 mg/ml.<br>Drug: Zofran<br>* Zofran 4 mg iv. in case of moderate to severe nausea, supplemented by Zofran 1 mg iv. if needed<br>|
| Placebo Comparator: Placebo<br>Oral administration of two placebo tablets Morphine. Patient controlled intravenous morphine (PCA-pump), bolus 2.5 mg, lock-out-time 10 minutes. Concentration : Morphin 1 mg/ml. Zofran 4 mg iv in case of moderate to severe nausea, supplemented by Zofran 1 mg iv if needed | Drug: Placebo<br>* Two placebo tablets identical to the chlorzoxazone tablets.<br>Drug: Morphine<br>* Patient controlled intravenous morphine (PCA-pump), bolus 2.5 mg, lock-out-time 10 minutes. Concentration : Morphin 1 mg/ml.<br>Drug: Zofran<br>* Zofran 4 mg iv. in case of moderate to severe nausea, supplemented by Zofran 1 mg iv. if needed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Painscore during mobilization | Painscore during active mobilization (VAS scale) defined by a standarized movement from recumbent position to sitting on the bedside | 2 hours after taking the trial medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morphine consumption | Total morphine consumption 0-4 hours after taking the trial medication, administered as patient controlled analgesia (PCA, bolus 2.5 mg, lockout 10 minutes). | 0-4 hours after taking the trial medication | 
| Painscore during rest | Painscore at rest (VAS)at time 1, 2, 3 and 4 hours, calculated as area under curve (AUC) from 1-4 hours after taking the trial medication. | 1, 2, 3 and 4 hours after taking the trial medication | 
| Painscore during mobilization | Painscore during active mobilization (VAS scale) defined by a standarized movement from recumbent position to sitting on the bedside at time 1, 2, 3 and 4 hours, calculated as area under curve (AUC) from 1-4 hours after taking the trial medication. | 1, 2, 3 and 4 hours after taking the trial medication | 
| Degree of nausea | Degree of nausea 1, 2, 3 and 4 hours after taking the trial medication. | 1, 2, 3 and 4 hours after taking the trial medication | 
| Zofran consumption | Consumption of Zofran (milligram) 0-4 hours after taking the trial medication. | 4 hours after taking the trial medication | 
| Degree of dizziness | Degree of dizziness 1, 2, 3 and 4 hours after taking the trial medication. | 1, 2, 3 and 4 hours after taking the trial medication | 
| Incidence of vomiting | Total number of vomits 0-4 hours after taking the trial medication. | 0-4 hours after taking the trial medication | 
| Degree of sedation | Degree of sedation 1, 2, 3 and 4 hours after taking the trial medication. | 1, 2, 3 and 4 hours after taking the trial medication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chlorzoxazone, Postoperative pain, Spine surgery, Opioid consumption