Total Knee ArthroplastyPhase 4NCT07485803
Methadone in the Management of Post-Operative Pain in Total Knee Replacement
A Phase 4 study testing Methadone in people with Total Knee Arthroplasty, run by AdventHealth at 1 site in United States.
Trial summary
The goal of this study is to determine whether one dose of IV methadone given right before surgery will help patients' pain management after a total knee replacement and reduce the amount of pain medications taken in the weeks after surgery. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Total Knee Arthroplasty
- What is being tested?
- Methadone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 192 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2026to Jun 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent from
- Stated willingness to comply with all study procedures and availability to attend all required visits for the duration of the study.
- Age 21- 75
- Unilateral total knee arthroplasty at Colorado Joint Replacement
- All individuals will be screened for drug use (opioid use, illicit drug use) at their preoperative appointment
- For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.
Who cannot join
- Narcotic use in the past 6 weeks
- Current or previous history of drug and alcohol abuse
- Tobacco use in the previous 90 days
- Treatment with another investigational drug
- Patients that cannot receive spinal anesthesia
- Patients that cannot receive the standardized multimodal pain medications (i.e. Tylenol, gabapentin and meloxicam)'
Show all 15Show fewer
- Patients that are not able to go home after leaving the hospital and require a short-term rehabilitation facility
- Obstructive sleep apnea
- Morbid obesity (BMI >40)
- Patients with liver disease.
- Significant kidney disease - stage 3 CKD or greater
- Pregnant or nursing females
- Baseline QTc >480
- severe COPD (GOLD 3 or 4)
- home oxygen requirement
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
AdventHealth Porter
Denver, Colorado, 80210
Makenna Hemmerle, 3032602951, makenna.hemmerle@adventhealth.com
About this study
Official title: A Prospective, Randomized Trial Utilizing Methadone in the Management of Post-Operative Pain in Total Knee Replacement
The goal of this study is to determine whether one dose of IV methadone given right before surgery will help patients' pain management after a total knee replacement and reduce the amount of pain medications taken in the weeks after surgery.
- Conditions
- Total Knee Arthroplasty
- Being tested
- Methadone
- Keywords
- pain management, TKA, methadone
- Medical subject headings
- Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethadoneDrug
Subjects randomized to receive methadone will be given one dose of methadone 0.15mg/kg intravenously dosed based on ideal body weight administered by the anesthesia team prior to surgical incision
| Study group | Role | What they receive |
|---|---|---|
| Methadone | Experimental | Patient will receive one perioperative dose of IV methadone prior to their surgical procedure in addition to standard of care medications. Receives: Drug: Methadone |
| No medication | No intervention | Patient will receive only the standard of care medications for their procedure. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Opioid use for 48 hours post-operatively
Opioid use will be calculated using morphine milligram equivalents (MME). Patients will keep a log to track opioid consumption.
Measured: 48 hours after TKA procedure
Secondary outcomes (7)
Defense and Veterans Pain Scale
Using the Defense and Veterans Pain Scale, patients will rate their pain ranging from 0 (no pain) to 10 (severe pain)
Measured: 2 weeks after TKA procedure
Opioid-Related Symptom Distress Scale (ORSDS)
4-point scale that evaluates 12 symptoms in 3 symptom categories including frequency, severity, and bothersomeness. The ORSDS may be used to calculate a symptom-specific score, which is the average of the 3 symptom distress dimensions and range from 0 to 4. The composite ORSDS score is the mean of all 12 symptom-specific scores. Composite ORSDS scores range from 0 to 4.
Measured: At baseline and 2 weeks after TKA procedure
Pittsburgh Sleep Quality Index
Patients will complete survey to monitor sleeping habits
Measured: At baseline and 2 weeks after TKA procedure
Total opioid usage over 2 weeks post-operatively
Opioid use will be calculated using morphine milligram equivalents (MME). Patients will keep a log to track opioid consumption.
Measured: 2 weeks after TKA procedure
Knee Society Score
This survey includes alignment, instability, joint range of motion, and symptoms. A higher score indicates good alignment, range of motion, and minimal symptoms of pain. A lower score indicates poor knee alignment, potential issues in range of motion, and the likely experience of symptoms of pain.
Measured: At baseline
KOOS-12 Knee Survey
This survey is used to evaluate knee pain, function and quality of life. The total score ranges from 0 to 100, where higher scores indicate better outcomes.
Measured: At baseline
Veterans Rand 12-Item Health Survey (VR-12)
This survey assesses overall health-related quality of life across physical and mental domains. It generates two summary scores-Physical Component Summary (PCS) and Mental Component Summary (MCS)-to provide a standardized evaluation of a patient's functional health and well-being.
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2026
- Study start1 Jun 2026
- Primary completionApr 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Total Knee ArthroplastyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 192 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AdventHealth
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07485803
- Sponsor's protocol ID
- 2387801
- Status last verified
- Mar 2026
- First submitted
- 17 Mar 2026
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kharasch ED. Intraoperative methadone: rediscovery, reappraisal, and reinvigoration? Anesth Analg. 2011 Jan;112(1):13-6. doi: 10.1213/ANE.0b013e3181fec9a3. No abstract available.
PubMed 21173206Komen H, Brunt LM, Deych E, Blood J, Kharasch ED. Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study. Anesth Analg. 2019 Apr;128(4):802-810. doi: 10.1213/ANE.0000000000003464.
PubMed 29847382Friesgaard KD, Brix LD, Kristensen CB, Rian O, Nikolajsen L. Clinical effectiveness and safety of intraoperative methadone in patients undergoing laparoscopic hysterectomy: a randomised, blinded clinical trial. BJA Open. 2023 Aug 5;7:100219. doi: 10.1016/j.bjao.2023.100219. eCollection 2023 Sep.
PubMed 37638083Morris BJ, Mir HR. The opioid epidemic: impact on orthopaedic surgery. J Am Acad Orthop Surg. 2015 May;23(5):267-71. doi: 10.5435/JAAOS-D-14-00163.
PubMed 25911660Menendez ME, Ring D, Bateman BT. Preoperative Opioid Misuse is Associated With Increased Morbidity and Mortality After Elective Orthopaedic Surgery. Clin Orthop Relat Res. 2015 Jul;473(7):2402-12. doi: 10.1007/s11999-015-4173-5. Epub 2015 Feb 19.
PubMed 25694266Cancienne JM, Patel KJ, Browne JA, Werner BC. Narcotic Use and Total Knee Arthroplasty. J Arthroplasty. 2018 Jan;33(1):113-118. doi: 10.1016/j.arth.2017.08.006. Epub 2017 Aug 17.
PubMed 28887020Li WT, Bell KL, Yayac M, Barmann JA, Star AM, Austin MS. A Postdischarge Multimodal Pain Management Cocktail Following Total Knee Arthroplasty Reduces Opioid Consumption in the 30-Day Postoperative Period: A Group-Randomized Trial. J Arthroplasty. 2021 Jan;36(1):164-172.e2. doi: 10.1016/j.arth.2020.07.060. Epub 2020 Jul 30.
PubMed 33036845
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized Trial Utilizing Methadone in the Management of Post-Operative Pain in Total Knee Replacement
- ClinicalTrials.gov ID
- NCT07485803
- Acronym / sponsor ID
- 2387801
- Conditions
- Total Knee Arthroplasty
- Keywords
- pain management, TKA, methadone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 192 participants (estimated)
- Lead sponsor
- AdventHealthUniversity, hospital or other
- Study start
- 1 Jun 2026 (actual)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 20 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to determine whether one dose of IV methadone given right before surgery will help patients' pain management after a total knee replacement and reduce the amount of pain medications taken in the weeks after surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methadone | Experimental | Drug: MethadonePatient will receive one perioperative dose of IV methadone prior to their surgical procedure in addition to standard of care medications. |
| No medication | No intervention | –Patient will receive only the standard of care medications for their procedure. |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Provision of signed and dated informed consent from
- Stated willingness to comply with all study procedures and availability to attend all required visits for the duration of the study.
- Age 21- 75
- Unilateral total knee arthroplasty at Colorado Joint Replacement
- All individuals will be screened for drug use (opioid use, illicit drug use) at their preoperative appointment
Key exclusion criteria (15 listed)
- Narcotic use in the past 6 weeks
- Current or previous history of drug and alcohol abuse
- Tobacco use in the previous 90 days
- Treatment with another investigational drug
- Patients that cannot receive spinal anesthesia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethadoneSubjects randomized to receive methadone will be given one dose of methadone 0.15mg/kg intravenously dosed based on ideal body weight administered by the anesthesia team prior to surgical incision | Drug | Methadone |
Primary outcome
Opioid use for 48 hours post-operatively
Time frame: 48 hours after TKA procedure
Opioid use will be calculated using morphine milligram equivalents (MME). Patients will keep a log to track opioid consumption.
7 secondary outcomes
Defense and Veterans Pain Scale
Time frame: 2 weeks after TKA procedure
Opioid-Related Symptom Distress Scale (ORSDS)
Time frame: At baseline and 2 weeks after TKA procedure
Pittsburgh Sleep Quality Index
Time frame: At baseline and 2 weeks after TKA procedure
Total opioid usage over 2 weeks post-operatively
Time frame: 2 weeks after TKA procedure
Knee Society Score
Time frame: At baseline
KOOS-12 Knee Survey
Time frame: At baseline
Veterans Rand 12-Item Health Survey (VR-12)
Time frame: At baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
- Background: PubMed 21173206Kharasch ED. Intraoperative methadone: rediscovery, reappraisal, and reinvigoration? Anesth Analg. 2011 Jan;112(1):13-6. doi: 10.1213/ANE.0b013e3181fec9a3. No abstract available.
- Background: PubMed 29847382Komen H, Brunt LM, Deych E, Blood J, Kharasch ED. Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study. Anesth Analg. 2019 Apr;128(4):802-810. doi: 10.1213/ANE.0000000000003464.
- Background: PubMed 37638083Friesgaard KD, Brix LD, Kristensen CB, Rian O, Nikolajsen L. Clinical effectiveness and safety of intraoperative methadone in patients undergoing laparoscopic hysterectomy: a randomised, blinded clinical trial. BJA Open. 2023 Aug 5;7:100219. doi: 10.1016/j.bjao.2023.100219. eCollection 2023 Sep.
- Background: PubMed 25911660Morris BJ, Mir HR. The opioid epidemic: impact on orthopaedic surgery. J Am Acad Orthop Surg. 2015 May;23(5):267-71. doi: 10.5435/JAAOS-D-14-00163.
- Background: PubMed 25694266Menendez ME, Ring D, Bateman BT. Preoperative Opioid Misuse is Associated With Increased Morbidity and Mortality After Elective Orthopaedic Surgery. Clin Orthop Relat Res. 2015 Jul;473(7):2402-12. doi: 10.1007/s11999-015-4173-5. Epub 2015 Feb 19.
- Background: PubMed 28887020Cancienne JM, Patel KJ, Browne JA, Werner BC. Narcotic Use and Total Knee Arthroplasty. J Arthroplasty. 2018 Jan;33(1):113-118. doi: 10.1016/j.arth.2017.08.006. Epub 2017 Aug 17.
- Background: PubMed 33036845Li WT, Bell KL, Yayac M, Barmann JA, Star AM, Austin MS. A Postdischarge Multimodal Pain Management Cocktail Following Total Knee Arthroplasty Reduces Opioid Consumption in the 30-Day Postoperative Period: A Group-Randomized Trial. J Arthroplasty. 2021 Jan;36(1):164-172.e2. doi: 10.1016/j.arth.2020.07.060. Epub 2020 Jul 30.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methadone in people with Total Knee Arthroplasty, run by AdventHealth at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Makenna Hemmerle (303-260-2951, makenna.hemmerle@adventhealth.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Opioid use for 48 hours post-operatively (time frame: 48 hours after TKA procedure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07485803, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2026.