Duloxetine Tibial Plateau

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Pain, Postoperative; Tibial Plateau Fracture
• Intervention / Treatment: Other: Placebo; Other: Standard of care (SOC) for tibial plateau surgery; Drug: Duloxetine

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • New York
    • Valhalla, New York, United States, 10595
      • Westchester Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Investigators: Principal Investigator: Seroos Salavati, MD, Boston Medical Center

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 1, 2022
• Primary Completion (ANTICIPATED): December 1, 2023
• Study Completion (ANTICIPATED): December 1, 2023

Study Registration Dates

• First Submitted: November 16, 2020
• First Submitted That Met QC Criteria: November 19, 2020
• First Posted (ACTUAL): November 20, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 21, 2022
• Last Update Submitted That Met QC Criteria: November 18, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Duloxetine; Patient Controlled Analgesia (PCA); VAS pain scores
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Serotonin Receptor Agonists; Serotonin and Noradrenaline Reuptake Inhibitors; Sympathomimetics; Vasoconstrictor Agents; Duloxetine Hydrochloride; Norepinephrine; Serotonin
• Other Study ID Numbers: H-40569

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes