Postoperative Pain and Analgesic Requirements After Preoperative Methadone for Primary TKA

Postoperative Pain and Analgesic Requirements After Preoperative Methadone for Primary Total Knee Arthroplasty, a Prospective, Randomized Study

The goal of this prospective, randomized study is to compare the outcomes of two cohorts of patients undergoing primary Total Knee Arthroplasty (TKA) and to determine whether a single dose of methadone administered preoperatively is effective at reducing postoperative opioid usage and postoperative pain versus a control group of patients receiving standard intraoperative opioids only for primary TKA.

The main questions it aims to answer are:

• What is the efficacy of a single preoperative dose of methadone in reducing opioid consumption and postoperative pain in primary total knee arthroplasty?
• Will the study results demonstrate the effectiveness and safety of a single preoperative dose of methadone (10 mg) in primary total knee arthroplasty in reducing postoperative opioid usage while maintaining a similar or better level of pain control when compared to a standard pain control regimen? Researchers will compare Methadone to a standard pain control regimen (Oxycodone) to see if Methadone is equivalent or more effective at reducing opioid consumption and postoperative pain in primary total knee arthroplasty

Participants will:

• be randomized into one of two groups
• undergo a primary TKA
• complete a tracking sheet documenting daily pain medicine usage and VAS pain level for the first 14 days following the TKA
• return to office at 2 weeks and 6 weeks postop for follow-up
• complete additional questionnaires at 2 weeks and 6 weeks postop

Study Overview

• Status: Completed
• Conditions: Osteoarthritis (OA) of the Knee
• Intervention / Treatment: Drug: Preoperative Methadone; Drug: Preoperative Oxycodone

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • UofL Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient age is 21-89 at time of surgery
2. Patient is scheduled to undergo a unilateral primary TKA, secondary to osteoarthritis
3. Patient agrees to participate as a study subject and signs the Informed Consent and Research Authorization document
4. Patient is able to read and speak English.

Exclusion Criteria:

1. Patient is under the age of 21
2. Patient's primary diagnosis is not osteoarthritis
3. Patient is unable to read and speak English
4. History of liver or kidney disease,
5. Known or suspected GI obstruction
6. Hypersensitivity to methadone
7. Patients with significant respiratory depression
8. Pregnant or nursing females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methadone Group; Participant receives a one-time preoperative dose of 10 mg of methadone	Drug: Preoperative Methadone; patient receives a one-time preoperative dose of 10 mg of methadone
Active Comparator: Oxycodone Group; participant receives a one-time preoperative dose of 10 mg of oral oxycodone	Drug: Preoperative Oxycodone; patient receives a one-time preoperative dose of 10 mg of oral oxycodone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily Opioid Use	Daily Opioid Use as measured in MME recorded daily for the first two weeks following TKA	2 weeks
Total opioid usage over two weeks	total daily opioid usage (as measured in MME) during the first 14 days following TKA	2 weeks
Visual Analogue Scale pain score	Visual Analogue Scale knee pain score (minimum value: 0, maximum value: 10). Higher scores equate to a worse outcome (a score of zero = pain free).	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Length of Stay	Number of days patient was an inpatient in the hospital prior to discharge date	Up to 2 weeks
Discharge location	Whether patient was discharged to home or to a rehab facility	2 weeks
Two and six-week narcotic refill	Whether patient was prescribed a two week and/or six-week postoperative narcotic refill	6 weeks
Knee Injury and Osteoarthritis Outcome Score, Joint Replacement score	The Knee Injury and Osteoarthritis Outcome Score, Joint Replacement (KOOS, JR.) is a survey measuring overall knee health for individuals post total knee arthroplasty (TKA) by evaluating stiffness, pain, function, and activities of daily living. The minimum value is 0, the maximum value is 100. A higher score means a better outcome.	preoperatively and 6 weeks (± 2 weeks) postoperatively
ROM	active range-of-motion (ROM) as measured in degrees of extension and degrees of flexion	preoperatively, 2 weeks and 6 weeks (± 2 weeks) postoperatively

Collaborators and Investigators

• Sponsor: University of Louisville
• Investigators: Study Chair: Rodolfo Zamora, MD, University of Louisville

Publications and helpful links

General Publications

• Bourne RB, Chesworth BM, Davis AM, Mahomed NN, Charron KD. Patient satisfaction after total knee arthroplasty: who is satisfied and who is not? Clin Orthop Relat Res. 2010 Jan;468(1):57-63. doi: 10.1007/s11999-009-1119-9.
• Duellman TJ, Gaffigan C, Milbrandt JC, Allan DG. Multi-modal, pre-emptive analgesia decreases the length of hospital stay following total joint arthroplasty. Orthopedics. 2009 Mar;32(3):167.
• Chui PT, Gin T. A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine. Anaesth Intensive Care. 1992 Feb;20(1):46-51. doi: 10.1177/0310057X9202000109.
• Bahreini M, Jalili M, Moradi-Lakeh M. A comparison of three self-report pain scales in adults with acute pain. J Emerg Med. 2015 Jan;48(1):10-8. doi: 10.1016/j.jemermed.2014.07.039. Epub 2014 Sep 27.
• Davis AM, Inturrisi CE. d-Methadone blocks morphine tolerance and N-methyl-D-aspartate-induced hyperalgesia. J Pharmacol Exp Ther. 1999 May;289(2):1048-53.
• Ferrari A, Coccia CP, Bertolini A, Sternieri E. Methadone--metabolism, pharmacokinetics and interactions. Pharmacol Res. 2004 Dec;50(6):551-9. doi: 10.1016/j.phrs.2004.05.002.
• Ebert B, Thorkildsen C, Andersen S, Christrup LL, Hjeds H. Opioid analgesics as noncompetitive N-methyl-D-aspartate (NMDA) antagonists. Biochem Pharmacol. 1998 Sep 1;56(5):553-9. doi: 10.1016/s0006-2952(98)00088-4.
• Aasvang EK, Lunn TH, Hansen TB, Kristensen PW, Solgaard S, Kehlet H. Chronic pre-operative opioid use and acute pain after fast-track total knee arthroplasty. Acta Anaesthesiol Scand. 2016 Apr;60(4):529-36. doi: 10.1111/aas.12667. Epub 2015 Dec 28.

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2024
• Primary Completion (Actual): September 24, 2024
• Study Completion (Actual): October 18, 2024

Study Registration Dates

• First Submitted: November 12, 2024
• First Submitted That Met QC Criteria: November 13, 2024
• First Posted (Actual): November 15, 2024

Study Record Updates

• Last Update Posted (Actual): November 15, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: osteoarthritis; knee; total knee arthroplasty; Methadone; preoperative analgesia; prospective RCT
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Postoperative Complications; Pathologic Processes; Arthritis; Joint Diseases; Rheumatic Diseases; Pain, Postoperative; Osteoarthritis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Methadone; Oxycodone
• Other Study ID Numbers: 23.0752

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Will not share IPD if it is not a requirement

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