Duloxetine Tibial Plateau

Study Overview
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Brief Summary
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The purpose of this study is to determine if Duloxetine provides effective pain management for adult patients (18 or older) undergoing tibial plateau surgery. Participants from two institutions will be randomized to one of two treatment groups: control (Group A) and treatment (Group B). Group A control group will receive placebo of sugar pill and BMC standard of care - namely postoperative, IV administration of opioids via a patient controlled analgesia (PCA) system which utilizes a hydromorphone pump (BMC standard of care). Group B, the intervention group, will receive three doses of 60 mg of oral duloxetine (right before operation, postop day 1, postop day 2). This study is important as tibial plateau surgery's postoperative pain management primarily involved providing opioids, and if duloxetine can result in reduced narcotic intake and lower pain scores, it can potentially improve patient care, rehabilitation, early movement, and shorter length of hospital stay.

Official Title
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Effects of Duloxetine on Postoperative Pain Control and Knee Rehabilitation After Open Reduction Internal Fixation of Tibial Plateau Fractures

Conditions
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Tibial Plateau Fracture, Pain, Postoperative

Intervention / Treatment
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* Drug: Duloxetine
* Other: Placebo
* Other: Standard of care (SOC) for tibial plateau surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Tibial plateau fracture that requires operative fixation Ambulatory patient prior to fracture Exclusion Criteria: Previous tibial plateau fracture on ipsilateral knee History of Complex Regional Pain Syndrome in ipsilateral extremity History of any demyelinating disorder or neurologic deficit that may contribute to altered pain tolerance/sensation Acute or chronic knee infection in ipsilateral extremity Previous total knee arthroplasty or knee hemiarthroplasty in ipsilateral knee Allergy to morphine (used in the SOC PCA pump) Pregnant or breastfeeding as determined by standard of care pre-operative urine pregnancy test Polytrauma Open fracture IV drug user Rheumatoid arthritis Revision cases Non-ambulatory Anatomical deformities of the knee Hepatic dysfunction or cirrhosis Taking Selective Serotonin Reuptake Inhibitor (SSRI), serotonin-norepinephrine reuptake Inhibitor (SNRI), monoamine oxidase inhibitors (MAOIs), tri- or tetra- cyclic anti-depressant Renal impairment (mention in patient chart and/or creatinine clearance <30) Moderate to severe depression Taking CYP1A2 inhibitors and CYP1A6 inhibitors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A Placebo<br>Participants randomized to Group A will receive placebo (sugar pill) and Boston Medical Center (BMC) standard of care. | Other: Placebo<br>* Three doses of placebo will be given to participants (right before operation, postop day 1, postop day 2).<br>* Other names: Sugar pill;Other: Standard of care (SOC) for tibial plateau surgery<br>* Postoperative IV administration of opioids via a patient controlled analgesia (PCA) system which utilizes a hydromorphone pump.<br>|
| Experimental: Groups B Intervention<br>Participants randomized to Group B will receive duloxetine and Boston Medical Center (BMC) standard of care. | Drug: Duloxetine<br>* Three doses of 60 mg of oral duloxetine will be given to participants (right before operation, postop day 1, postop day 2)<br>* Other names: Serotonin-norepinephrine reuptake inhibitor (SNRI);Other: Standard of care (SOC) for tibial plateau surgery<br>* Postoperative IV administration of opioids via a patient controlled analgesia (PCA) system which utilizes a hydromorphone pump.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain levels in the first 16 hours after surgery | A visual analog pain scale (VAS) will be used to assess postoperative pain levels. Participants will make a mark on a 10-cm line that represents a continuum between no pain and worst pain. HIgher scores reflect greater pain levels. | every 4 hours up to 16 hours | 
| Pain level 24 hours after surgery | A visual analog pain scale (VAS) will be used to assess the postoperative pain level. Participants will make a mark on a 10-cm line that represents a continuum between no pain and worst pain. HIgher scores reflect greater pain levels. | 24 hours | 
| Pain level 36 hours after surgery | A visual analog pain scale (VAS) will be used to assess the postoperative pain level. Participants will make a mark on a 10-cm line that represents a continuum between no pain and worst pain. HIgher scores reflect greater pain levels. | 36 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total morphine consumption | The total morphine consumption will be calculated using the Centers for Disease Control (CDC) morphine equivalents [ME].Determine the total daily amount of morphine taken; convert to MEs by multiplying the daily dosage for each opioid by its conversion factor [which is =1 for morphine]; then add all morphine MEs together. | up to 10 days post op | 
| Change in knee range of motion | The knee range of motion will be abstracted from the electronic medical record. Knee range of motion ranges from 0 to 140 degrees. | 6 weeks, 12 weeks | 
| Self reported functional status at 6 weeks | Functional status will be assessed using the Short Musculoskeletal Function Assessment (SMFA). SMFA is a 46 item questionnaire. It consists of the dysfunction index, which has 34 items for the assessment of patient function, and the bother index, which has 12 items for the assessment of how much patients are bothered by functional problems. | 6 weeks | 
| Self reported functional status at 12 weeks | Functional status will be assessed using the Short Musculoskeletal Function Assessment (SMFA). SMFA is a 46 item questionnaire. It consists of the dysfunction index, which has 34 items for the assessment of patient function, and the bother index, which has 12 items for the assessment of how much patients are bothered by functional problems. | 12 weeks | 
| Hospital length of stay | The hospital length of stay will be measured in days, calculated by subtracting the date of admission from the date of discharge as recorded in the electronic medical record. | 12 weeks | 
| Time to mobilization (starting to walk) | The time to mobilization will be calculated by subtracting the date the participant started to walk post operatively from the date of surgery as recorded in the electronic medical record. | 12 weeks | 
| Ambulation (walking) distance on post-op days 1 or 2 | The walking distance will be abstracted from the electronic medical record. | Up to 2 days post op | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Duloxetine, VAS pain scores, Patient Controlled Analgesia (PCA)