Pain, PostoperativePhase 4BAFANCT06949826
Buprenorphine as a Post-operative Analgesic in Opioid-Naive Patients After Ankle Fracture Surgery
A Phase 4 study testing Buprenorphine Transdermal System in people with Pain, Postoperative and Ankle Fracture Surgery, run by Jenna-Leigh Wilson at 1 site in United States.
Trial summary
Addictive full-agonist opioids, like oxycodone and hydrocodone, are often used to treat pain after surgery. However, these full-agonist opioids can be very addictive. After ankle fracture surgery, about 1 in 5 patients that did not take opioids before surgery become addicted to opioids after surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain, Postoperative, Ankle Fracture Surgery, Opioid Use Disorder
- What is being tested?
- Buprenorphine Transdermal System
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Apr 2025to Jun 2027
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient is 18 years of age or older
- Patient is undergoing single stage ORIF of an ankle fracture
- Patient is English-speaking
Who cannot join
- Patient is under 18 years of age
- Patient's ankle fracture is treated with external fixation
- Patient has a concomitant osseous or visceral injury
- Patient has a history of opioid use disorder or a current diagnosis of opioid use disorder
- Patient has a history of alcohol use disorder or a current diagnosis of alcohol use disorder
- Patient was taking opioid medication or narcotic drugs prior to their injury
Show all 14Show fewer
- Patient has a current active malignancy
- Patient is taking a medication that carries a prohibitively high risk of drug-drug interaction with buprenorphine, hydrocodone, or oxycodone in the view of their treating physician or nurse anesthetist
- Patient has an anaphylactic allergy to buprenorphine, hydrocodone, or oxycodone
- Patient is not English-speaking
- Patient is pregnant
- Patient is unable to complete pain diary or communicate pain scores
- Patient is incarcerated
- Patient has a Gustilo-Anderson Type III open fracture
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
Washington University in St. Louis/Barnes Jewish Hospital
St Louis, Missouri, 63110
Noah J Harrison, MD, MMSc, 314-459-1140, nharrison@wustl.edu
Juanita R Tylor, MPA, BS, RRT, 314-454-7047, jrtaylor@wustl.edu
About this study
Official title: A Single-institution, Parallel, Double-blinded, Randomized Study Assessing the Safety and Efficacy of Transdermal Buprenorphine as a Post-operative Analgesic in Opioid-Naive Patients After Ankle Fracture Surgery
Addictive full-agonist opioids, like oxycodone and hydrocodone, are often used to treat pain after surgery. However, these full-agonist opioids can be very addictive. After ankle fracture surgery, about 1 in 5 patients that did not take opioids before surgery become addicted to opioids after surgery. Buprenorphine is an opioid with unique properties that may offer a way to reduce the number of patients that become addicted to opioids after surgery. Buprenorphine has good analgesic (painkilling) effects. It is also thought to be less addictive and cause less of a high than full-agonist opioids, like oxycodone and hydrocodone. This project's goal is to determine if transdermal buprenorphine can safely and effectively control pain after ankle fracture surgery. This study will be a pilot study, which sets the stage for future studies that investigate whether buprenorphine can reduce the rate that patients become addicted to opioids after surgery. This study's multidisciplinary team will divide patients into two groups. Participants in one group will be treated with a 7-day transdermal buprenorphine patch (where the buprenorphine is slowly absorbed through the skin over 7 days). Participants in the other group will be treated with a placebo patch. A placebo has no drug in it, it just looks like the buprenorphine patch. Aside from the buprenorphine patch or placebo patch, both groups' pain management plans will be the same as if they were not in the study. Over the first week after surgery, the investigators will measure the amount of full-agonist opioids (for example, oxycodone or hydrocodone) that participants consume, participants' pain scores, the frequency of side effects related to opioids, and the number of calls and patient portal messages to the clinic for uncontrolled pain. The investigators will also assess whether participants are continuing to use opioids 3 months after surgery for pain related to their ankle fracture.
Read the detailed description
Addictive full-agonist opioids, like oxycodone, remain a staple of post-operative analgesia after many types of surgery. However, perioperative exposure to opioid analgesics risks addiction in up to 7% of cases. Moreover, opioid overdoses kill over 80,000 in the United States (US) annually. Buprenorphine, a partial-agonist of the μ-opioid receptor and an antagonist of the κ-opioid receptor, may be able to safely function as a post-operative analgesic, reducing our reliance on full-agonist opioids post-operatively. Compared to full-agonist opioids, buprenorphine has a favorable safety profile. It has been hypothesized that buprenorphine's unique pharmacodynamics give it a lower addictive potential compared to full-agonist opioids. Moreover, it endows a ceiling on respiratory depression, has reduced dysphoric and psychotomimetic effects, and does not result in immunosuppression at therapeutic analgesic doses. International studies have suggested that transdermal buprenorphine is noninferior to tramadol, transdermal fentanyl, and oral celecoxib in the management of acute post-operative pain in opioid-naïve patients following orthopaedic surgery. However, the efficacy of buprenorphine for postoperative analgesia has never been studied in the United States, whose population has different beliefs and expectations surrounding pain control when compared to international populations. The major goal of this project is to determine the safety and efficacy of transdermal buprenorphine for postoperative analgesia, as a first step toward exploring the ability of buprenorphine to mitigate the incidence of opioid dependence in the postoperative setting.
This study will assess whether buprenorphine can reduce the use of full-agonist opioids following ankle fracture surgery. Approximately one in five opioid-naïve patients undergoing ankle fracture surgery continue to use opioids 3 to 6 months out from surgery, suggesting that this population is relatively susceptible to developing post-operative opioid dependence. The investigators will divide patients into two groups. One group will be treated with a 7-day transdermal buprenorphine patch. The other will be treated with a placebo patch. Both groups will otherwise receive a post-operative pain management regimen that is in accordance with the standard of care. The investigators hypothesize that participants treated with the buprenorphine patch will experience improved analgesia with the use fewer full-agonist opioids following ankle fracture surgery than those treated with the placebo patch. This hypothesis will be tested with the following aims.
Specific Aim 1: To measure the analgesic effect of buprenorphine on post-operative analgesia. In this Aim, the investigators will test the hypothesis that use of buprenorphine patches will reduce the average pain scores and consumption of full-agonist opioids after ankle fracture surgery. In sub-Aim 1.1, the investigators will quantify postoperative pain by monitoring participants' visual analog scale pain scores and full-agonist opioid consumption over the first post-operative week. In sub-Aim 1.2, the investigators will track the number of episodes of breakthrough pain in the hospital, the number of calls to the clinic with a chief complaint of uncontrolled pain, and the number of presentations to an emergency department for uncontrolled surgery-related pain.
Specific Aim 2: To examine the safety of buprenorphine as a post-operative analgesic following ankle fracture surgery. In this Aim, the investigators will test the hypothesis that participants treated with buprenorphine patches will experience fewer adverse events related to opioid exposure compared to those treated with placebo patches. The investigators will monitor for adverse effects of buprenorphine and full-agonist opioids, including respiratory depression, constipation, nausea, and vomiting. The investigators will track the number of presentations to an emergency department with a diagnosis of opioid toxicity. For pilot data, the investigators will also monitor use of opioids for analgesia at the 3-month postoperative time point as a secondary outcome.
This study assesses whether buprenorphine safely reduces full-agonist opioid use after orthopaedic surgery. Completion of the Aims of this study will permit future studies assessing whether buprenorphine comprises a less-addictive alternative for postoperative analgesia compared to full-agonist opioids. Annually, there are 40-50 million major surgeries performed in the US. As 6-7% of opioid-naïve patients develop long-term opioid use after major surgery, exploring avenues to decrease the impact of post-operative analgesia on the opioid epidemic is critical.
- Conditions
- Pain, Postoperative, Ankle Fracture Surgery, Opioid Use Disorder, Opioid Dependence, Opioid Analgesia
- Being tested
- Buprenorphine Transdermal System, Placebo Patch
- Keywords
- Buprenorphine, Postoperative pain, Transdermal buprenorphine, Ankle fracture surgery, Ankle fracture, Opioid-naive patient, ORIF Ankle Fracture, Opioid use disorder, Opioid Addiction, Buprenorphine for postoperative pain
- Medical subject headings
- Pain, Postoperative, Opioid-Related Disorders, Ankle Fractures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Buprenorphine Transdermal SystemDrug
The buprenorphine transdermal system is unique from other interventions in the study, as it is the experimental drug in the study. The buprenorphine transdermal system will be applied in the pre-operative holding area. Aside from the buprenorphine transdermal system, participants assigned to this intervention will otherwise receive the standard of care in their post-operative pain management following ankle fracture surgery.
Placebo PatchDrug
The placebo patch is unique from other interventions in the study, as it is the placebo drug in the study. The placebo patch will be applied in the pre-operative holding area. Aside from the placebo patch, participants assigned to this intervention will otherwise receive the standard of care in their post-operative pain management following ankle fracture surgery.
| Study group | Role | What they receive |
|---|---|---|
| Buprenorphine Transdermal System | Experimental | Participants in this arm will be treated with the transdermal buprenorphine system (a transdermal patch) that is applied in the pre-operative holding area. Aside from being treated with the transdermal buprenorphine system, their care will otherwise be in accordance with the standard of care following ankle fracture surgery. Receives: Drug: Buprenorphine Transdermal System |
| Placebo Patch | Placebo comparator | Participants in this arm will be treated with a placebo patch that is applied in the pre-operative holding area. Aside from the placebo patch, their care will otherwise be in accordance with the standard of care following ankle fracture surgery. Receives: Drug: Placebo Patch |
What is being measured
The primary outcome is the main question the study is designed to answer.
Morphine Milligram Equivalents of Full-agonist Opioid Consumed
After surgery, patients will record the total amount of opioid medication they consumed during the first post-operative week in their pain diary. In admitted patients, the electronic medical record will be reviewed to determine the morphine milligram equivalents of opioid consumed while admitted. Patients will also bring all their bottles and opioid prescriptions to their first post-operative clinic visit, at which point their total opioid consumption between surgery and their first post-operative clinic visit will be recorded by the researchers.
Measured: Post-operative days 0-7. First post-operative clinic visit (approximately 3 weeks after surgery).
Secondary outcomes (18)
Visual Analog Pain Scores
After surgery, visual analog pain scores with movement and at rest will be reported by the patient in a pain diary. In admitted patients, visual analog pain scores will be recorded by the bedside nurse. Visual analog pain scores are rated from 0-10. A score of 0 represents that the patient has no pain. A score of 10 represents excruciating pain.
Measured: Postoperative days 1-8, 21, 90.
Morphine Milligram Equivalents of Full-Agonist Opioids Administered in Perioperative Setting
Review of the medication administration record will be performed to calculate the morphine milligram equivalents of opioid medication administered during ankle fracture surgery and in the post-operative recovery unit.
Measured: Perioperative/Periprocedural
Adverse Effects Related to Opioid Medication
After surgery, patients will record whether they have symptoms of constipation, nausea, vomiting, drowsiness, or anything other symptoms potentially related to their opioid medication. The frequency and types of adverse effects will be recorded by the study researchers.
Measured: Post-operative days 1-8, 21.
Hospital Readmissions due to Uncontrolled Post-operative Pain
The investigators will track the number of hospital readmissions due to uncontrolled post-operative pain.
Measured: From patch application through post-operative day 21.
Emergency Department Presentations due to Uncontrolled Pain
The investigators will track the number of emergency department presentations, with a chief complaint of uncontrolled post-operative pain.
Measured: From patch application through post-operative day 21.
Emergency Department Presentations due to Opioid Toxicity
The researchers will track the number of presentations to the emergency department with a chief complaint of opioid toxicity.
Measured: From patch application to post-operative day 21
Hospital Readmissions due to Opioid Toxicity
The researchers will track the number of hospital readmissions secondary to opioid toxicity.
Measured: From patch application to post-operative day 21
Time from Surgery Completion to Discharge
For patients undergoing outpatient surgery, review of the electronic medical record will be performed to determine the time from surgery completion to discharge.
Measured: Perioperative/periprocedural
Hospital Length of Stay
For patients being admitted to the hospital to recover after ankle fracture surgery, review of the electronic medical record will be performed to determine the average hospital length of stay for each group.
Measured: From the completion of ankle fracture surgery to hospital discharge.
Number of Breakthrough Pain Episodes while Inpatient
For patients admitted after surgery, the number of breakthrough pain episodes while inpatient will be determined. A breakthrough pain episode will be defined as a sudden, severe, brief pain occurring in the setting go f adequately controlled mild-moderate background pain. It will be denoted by the administration of a medication in the inpatient setting with an indication of "for breakthrough pain."
Measured: Post-operative day 0 through hospital discharge
Quality of Recovery after Anesthesia 15-Question Survey
Patients will complete the quality of recovery after anesthesia 15-question survey. Scores range from 0 to 150. A score of 0 represents a poor recovery after anesthesia. A score of 150 represents an excellent recover after anesthesia.
Measured: Post-operative day 7
Telephone Calls and MyChart Messages to Clinic or Call Center with a Chief Complaint of Uncontrolled Pain
Review of the electronic medical record will be performed to record the average number of telephone calls and MyChart messages to the orthopaedic surgery clinic or call center with a chief complaint of uncontrolled pain.
Measured: Post-operative days 0-21.
Opioid Medication Prescriptions - Number and Total Morphine Milligram Equivalents Prescribed
The researchers will review the electronic medical record to record the number of opioid medication prescriptions requested and filled by the patient.
Measured: From the time of injury through post-operative day 90.
Drug Liking and Economic Choice Survey
Patients will be asked by questionnaire how much they liked their buprenorphine vs placebo patch and oral narcotic prescriptions, as well as how much they would pay for their buprenorphine vs placebo patch and oral full-agonist opioid prescription.
Measured: Post-operative days 7, 21, 90
Patient Satisfaction with Post-operative Pain Control
Patient satisfaction with their post-operative pain control will be recorded by questionnaire in the form of a Likert scale.
Measured: Post-operative days 7, 21
Rate of Persistent Opioid Use
Approximately three months after surgery, patients will record whether they are continuing to take opioids/narcotics for pain related to their ankle fracture surgery.
Measured: Post-operative day 90
Prescription Pain Medication Misuse Short Form 7a Scores
Patients will complete the PROMIS Prescription Pain Medication Misuse Short Form 7a. Scores will be tabulated from 0 to 35. A score of 35 represents a high level of pain medication misuse. A score of 0 represents a low level of pain medication misuse.
Measured: Post-operative day 90
Post-operative Complication Rate
The researchers will review the electronic medical record to the rate and type of post-operative complications after ankle fracture surgery.
Measured: Post-operative days 0-90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2025
- Study start21 Apr 2025
- Primary completionMar 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (32)Papers the sponsor has linked to this study.
- Other trials for Pain, PostoperativeStudies 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jenna-Leigh Wilson
- Sponsor type
- University, hospital or other
- Collaborators
- The Foundation for Barnes-Jewish Hospital, Washington University Institute of Clinical and Translational Sciences
- Responsible party
- Sponsor-investigator, Jenna-Leigh Wilson, Washington University School of Medicine
- Investigators
- Jenna Wilson, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06949826
- Sponsor's protocol ID
- 202406162
- Acronym
- BAFA
- Status last verified
- Mar 2026
- First submitted
- 11 Apr 2025
- Last updated
- 6 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: After deidentification, all individual participant data may be shared.
Publications
Lawal OD, Gold J, Murthy A, Ruchi R, Bavry E, Hume AL, Lewkowitz AK, Brothers T, Wen X. Rate and Risk Factors Associated With Prolonged Opioid Use After Surgery: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020 Jun 1;3(6):e207367. doi: 10.1001/jamanetworkopen.2020.7367.
PubMed 32584407Vadivelu N, Hines RL. Buprenorphine: a unique opioid with broad clinical applications. J Opioid Manag. 2007 Jan-Feb;3(1):49-58. doi: 10.5055/jom.2007.0038.
PubMed 17367094Jasinski DR, Pevnick JS, Griffith JD. Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction. Arch Gen Psychiatry. 1978 Apr;35(4):501-16. doi: 10.1001/archpsyc.1978.01770280111012.
PubMed 215096Walsh SL, Babalonis S. The Abuse Potential of Prescription Opioids in Humans-Closing in on the First Century of Research. Curr Top Behav Neurosci. 2017;34:33-58. doi: 10.1007/7854_2016_448.
PubMed 27356522Walsh SL, Preston KL, Stitzer ML, Cone EJ, Bigelow GE. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther. 1994 May;55(5):569-80. doi: 10.1038/clpt.1994.71.
PubMed 8181201Kress HG. Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine. Eur J Pain. 2009 Mar;13(3):219-30. doi: 10.1016/j.ejpain.2008.04.011. Epub 2008 Jun 24.
PubMed 18567516Pergolizzi JV Jr, Magnusson P, LeQuang JA, Breve F, Mitchell K, Chopra M, Varrassi G. Transdermal Buprenorphine for Acute Pain in the Clinical Setting: A Narrative Review. J Pain Res. 2021 Mar 31;14:871-879. doi: 10.2147/JPR.S280572. eCollection 2021.
PubMed 33833565Desai SN, Badiger SV, Tokur SB, Naik PA. Safety and efficacy of transdermal buprenorphine versus oral tramadol for the treatment of post-operative pain following surgery for fracture neck of femur: A prospective, randomised clinical study. Indian J Anaesth. 2017 Mar;61(3):225-229. doi: 10.4103/ija.IJA_208_16.
PubMed 28405035Arshad Z, Prakash R, Gautam S, Kumar S. Comparison between Transdermal Buprenorphine and Transdermal Fentanyl for Postoperative Pain Relief after Major Abdominal Surgeries. J Clin Diagn Res. 2015 Dec;9(12):UC01-4. doi: 10.7860/JCDR/2015/16327.6917. Epub 2015 Dec 1.
PubMed 26816973Kim HJ, Ahn HS, Nam Y, Chang BS, Lee CK, Yeom JS. Comparative study of the efficacy of transdermal buprenorphine patches and prolonged-release tramadol tablets for postoperative pain control after spinal fusion surgery: a prospective, randomized controlled non-inferiority trial. Eur Spine J. 2017 Nov;26(11):2961-2968. doi: 10.1007/s00586-017-5213-5. Epub 2017 Jul 20.
PubMed 28730328Londhe S, Patwardhan M, Shah R, Oak M. Efficacy and Safety of Buprenorphine Transdermal Patch for Immediate Postoperative Analgesia After Total Knee Arthroplasty Surgery. J Arthroplasty. 2020 Jun;35(6S):S178-S181. doi: 10.1016/j.arth.2020.02.015. Epub 2020 Feb 13.
PubMed 32201109Londhe SB, Patwardhan M, Shah RV, Oak M, Shah A, Antao N, Khot R. Comparison of Efficacy and Safety of Transdermal Buprenorphine Patch and Conventional Analgesics in Intra-capsular Femur Neck Fracture Post Hemiarthroplasty. Indian J Orthop. 2022 Jun 25;56(8):1363-1369. doi: 10.1007/s43465-022-00668-7. eCollection 2022 Aug.
PubMed 35928664Niyogi S, Bhunia P, Nayak J, Santra S, Acharjee A, Chakraborty I. Efficacy of transdermal buprenorphine patch on post-operative pain relief after elective spinal instrumentation surgery. Indian J Anaesth. 2017 Nov;61(11):923-929. doi: 10.4103/ija.IJA_118_17.
PubMed 29217859Setti T, Sanfilippo F, Leykin Y. Transdermal buprenorphine for postoperative pain control in gynecological surgery: a prospective randomized study. Curr Med Res Opin. 2012 Oct;28(10):1597-608. doi: 10.1185/03007995.2012.719864. Epub 2012 Sep 10.
PubMed 22876835Xu X, Xie L, Liu H, Hu Y. Transdermal buprenorphine patch versus oral celecoxib for pain management after total knee arthroplasty: An open- label, randomized controlled trial. Orthop Traumatol Surg Res. 2020 Sep;106(5):915-919. doi: 10.1016/j.otsr.2020.04.010. Epub 2020 Jul 2.
PubMed 32624377
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-institution, Parallel, Double-blinded, Randomized Study Assessing the Safety and Efficacy of Transdermal Buprenorphine as a Post-operative Analgesic in Opioid-Naive Patients After Ankle Fracture Surgery
- ClinicalTrials.gov ID
- NCT06949826
- Acronym / sponsor ID
- BAFA / 202406162
- Conditions
- Pain, Postoperative, Ankle Fracture Surgery, Opioid Use Disorder, Opioid Dependence, Opioid Analgesia
- Keywords
- Buprenorphine, Postoperative pain, Transdermal buprenorphine, Ankle fracture surgery, Ankle fracture, Opioid-naive patient, ORIF Ankle Fracture, Opioid use disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Jenna-Leigh WilsonUniversity, hospital or other
- Collaborators
- The Foundation for Barnes-Jewish Hospital, Washington University Institute of Clinical and Translational Sciences
- Study start
- 21 Apr 2025 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 29 Apr 2025 (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.
Addictive full-agonist opioids, like oxycodone and hydrocodone, are often used to treat pain after surgery. However, these full-agonist opioids can be very addictive. After ankle fracture surgery, about 1 in 5 patients that did not take opioids before surgery become addicted to opioids after surgery. Buprenorphine is an opioid with unique properties that may offer a way to reduce the number of patients that become addicted to opioids after surgery. Buprenorphine has good analgesic (painkilling) effects. It is also thought to be less addictive and cause less of a high than full-agonist opioids, like oxycodone and hydrocodone. This project's goal is to determine if transdermal buprenorphine can safely and effectively control pain after ankle fracture surgery. This study will be a pilot study, which sets the stage for future studies that investigate whether buprenorphine can reduce the rate that patients become addicted to opioids after surgery. This study's multidisciplinary team will divide patients into two groups. Participants in one group will be treated with a 7-day transdermal buprenorphine patch (where the buprenorphine is slowly absorbed through the skin over 7 days). Participants in the other group will be treated with a placebo patch. A placebo has no drug in it, it just looks like the buprenorphine patch. Aside from the buprenorphine patch or placebo patch, both groups' pain management plans will be the same as if they were not in the study. Over the first week after surgery, the investigators will measure the amount of full-agonist opioids (for example, oxycodone or hydrocodone) that participants consume, participants' pain scores, the frequency of side effects related to opioids, and the number of calls and patient portal messages to the clinic for uncontrolled pain. The investigators will also assess whether participants are continuing to use opioids 3 months after surgery for pain related to their ankle fracture.
Detailed description
Addictive full-agonist opioids, like oxycodone, remain a staple of post-operative analgesia after many types of surgery. However, perioperative exposure to opioid analgesics risks addiction in up to 7% of cases. Moreover, opioid overdoses kill over 80,000 in the United States (US) annually. Buprenorphine, a partial-agonist of the μ-opioid receptor and an antagonist of the κ-opioid receptor, may be able to safely function as a post-operative analgesic, reducing our reliance on full-agonist opioids post-operatively. Compared to full-agonist opioids, buprenorphine has a favorable safety profile. It has been hypothesized that buprenorphine's unique pharmacodynamics give it a lower addictive potential compared to full-agonist opioids. Moreover, it endows a ceiling on respiratory depression, has reduced dysphoric and psychotomimetic effects, and does not result in immunosuppression at therapeutic analgesic doses. International studies have suggested that transdermal buprenorphine is noninferior to tramadol, transdermal fentanyl, and oral celecoxib in the management of acute post-operative pain in opioid-naïve patients following orthopaedic surgery. However, the efficacy of buprenorphine for postoperative analgesia has never been studied in the United States, whose population has different beliefs and expectations surrounding pain control when compared to international populations. The major goal of this project is to determine the safety and efficacy of transdermal buprenorphine for postoperative analgesia, as a first step toward exploring the ability of buprenorphine to mitigate the incidence of opioid dependence in the postoperative setting.
This study will assess whether buprenorphine can reduce the use of full-agonist opioids following ankle fracture surgery. Approximately one in five opioid-naïve patients undergoing ankle fracture surgery continue to use opioids 3 to 6 months out from surgery, suggesting that this population is relatively susceptible to developing post-operative opioid dependence. The investigators will divide patients into two groups. One group will be treated with a 7-day transdermal buprenorphine patch. The other will be treated with a placebo patch. Both groups will otherwise receive a post-operative pain management regimen that is in accordance with the standard of care. The investigators hypothesize that participants treated with the buprenorphine patch will experience improved analgesia with the use fewer full-agonist opioids following ankle fracture surgery than those treated with the placebo patch. This hypothesis will be tested with the following aims.
Specific Aim 1: To measure the analgesic effect of buprenorphine on post-operative analgesia. In this Aim, the investigators will test the hypothesis that use of buprenorphine patches will reduce the average pain scores and consumption of full-agonist opioids after ankle fracture surgery. In sub-Aim 1.1, the investigators will quantify postoperative pain by monitoring participants' visual analog scale pain scores and full-agonist opioid consumption over the first post-operative week. In sub-Aim 1.2, the investigators will track the number of episodes of breakthrough pain in the hospital, the number of calls to the clinic with a chief complaint of uncontrolled pain, and the number of presentations to an emergency department for uncontrolled surgery-related pain.
Specific Aim 2: To examine the safety of buprenorphine as a post-operative analgesic following ankle fracture surgery. In this Aim, the investigators will test the hypothesis that participants treated with buprenorphine patches will experience fewer adverse events related to opioid exposure compared to those treated with placebo patches. The investigators will monitor for adverse effects of buprenorphine and full-agonist opioids, including respiratory depression, constipation, nausea, and vomiting. The investigators will track the number of presentations to an emergency department with a diagnosis of opioid toxicity. For pilot data, the investigators will also monitor use of opioids for analgesia at the 3-month postoperative time point as a secondary outcome.
This study assesses whether buprenorphine safely reduces full-agonist opioid use after orthopaedic surgery. Completion of the Aims of this study will permit future studies assessing whether buprenorphine comprises a less-addictive alternative for postoperative analgesia compared to full-agonist opioids. Annually, there are 40-50 million major surgeries performed in the US. As 6-7% of opioid-naïve patients develop long-term opioid use after major surgery, exploring avenues to decrease the impact of post-operative analgesia on the opioid epidemic is critical.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Buprenorphine Transdermal System | Experimental | Drug: Buprenorphine Transdermal SystemParticipants in this arm will be treated with the transdermal buprenorphine system (a transdermal patch) that is applied in the pre-operative holding area. Aside from being treated with the transdermal buprenorphine system, their care will otherwise be in accordance with the standard of care following ankle fracture surgery. |
| Placebo Patch | Placebo comparator | Drug: Placebo PatchParticipants in this arm will be treated with a placebo patch that is applied in the pre-operative holding area. Aside from the placebo patch, their care will otherwise be in accordance with the standard of care following ankle fracture surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patient is 18 years of age or older
- Patient is undergoing single stage ORIF of an ankle fracture
- Patient is English-speaking
Key exclusion criteria (14 listed)
- Patient is under 18 years of age
- Patient's ankle fracture is treated with external fixation
- Patient has a concomitant osseous or visceral injury
- Patient has a history of opioid use disorder or a current diagnosis of opioid use disorder
- Patient has a history of alcohol use disorder or a current diagnosis of alcohol use disorder
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 |
|---|---|---|
| Buprenorphine Transdermal SystemThe buprenorphine transdermal system is unique from other interventions in the study, as it is the experimental drug in the study. The buprenorphine transdermal system will be applied in the pre-operative holding area. Aside from the buprenorphine transdermal system, participants assigned to this intervention will otherwise receive the standard of care in their post-operative pain management following ankle fracture surgery. | Drug | Buprenorphine Transdermal System |
| Placebo PatchThe placebo patch is unique from other interventions in the study, as it is the placebo drug in the study. The placebo patch will be applied in the pre-operative holding area. Aside from the placebo patch, participants assigned to this intervention will otherwise receive the standard of care in their post-operative pain management following ankle fracture surgery. | Drug | Placebo Patch |
Primary outcome
Morphine Milligram Equivalents of Full-agonist Opioid Consumed
Time frame: Post-operative days 0-7. First post-operative clinic visit (approximately 3 weeks after surgery).
After surgery, patients will record the total amount of opioid medication they consumed during the first post-operative week in their pain diary. In admitted patients, the electronic medical record will be reviewed to determine the morphine milligram equivalents of opioid consumed while admitted. Patients will also bring all their bottles and opioid prescriptions to their first post-operative clinic visit, at which point their total opioid consumption between surgery and their first post-operative clinic visit will be recorded by the researchers.
18 secondary outcomes
Visual Analog Pain Scores
Time frame: Postoperative days 1-8, 21, 90.
Morphine Milligram Equivalents of Full-Agonist Opioids Administered in Perioperative Setting
Time frame: Perioperative/Periprocedural
Adverse Effects Related to Opioid Medication
Time frame: Post-operative days 1-8, 21.
Hospital Readmissions due to Uncontrolled Post-operative Pain
Time frame: From patch application through post-operative day 21.
Emergency Department Presentations due to Uncontrolled Pain
Time frame: From patch application through post-operative day 21.
Emergency Department Presentations due to Opioid Toxicity
Time frame: From patch application to post-operative day 21
Hospital Readmissions due to Opioid Toxicity
Time frame: From patch application to post-operative day 21
Time from Surgery Completion to Discharge
Time frame: Perioperative/periprocedural
Hospital Length of Stay
Time frame: From the completion of ankle fracture surgery to hospital discharge.
Number of Breakthrough Pain Episodes while Inpatient
Time frame: Post-operative day 0 through hospital discharge
Quality of Recovery after Anesthesia 15-Question Survey
Time frame: Post-operative day 7
Telephone Calls and MyChart Messages to Clinic or Call Center with a Chief Complaint of Uncontrolled Pain
Time frame: Post-operative days 0-21.
Opioid Medication Prescriptions - Number and Total Morphine Milligram Equivalents Prescribed
Time frame: From the time of injury through post-operative day 90.
Drug Liking and Economic Choice Survey
Time frame: Post-operative days 7, 21, 90
Patient Satisfaction with Post-operative Pain Control
Time frame: Post-operative days 7, 21
Rate of Persistent Opioid Use
Time frame: Post-operative day 90
Prescription Pain Medication Misuse Short Form 7a Scores
Time frame: Post-operative day 90
Post-operative Complication Rate
Time frame: Post-operative days 0-90
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 6 Apr 2026.
- Background: PubMed 32584407Lawal OD, Gold J, Murthy A, Ruchi R, Bavry E, Hume AL, Lewkowitz AK, Brothers T, Wen X. Rate and Risk Factors Associated With Prolonged Opioid Use After Surgery: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020 Jun 1;3(6):e207367. doi: 10.1001/jamanetworkopen.2020.7367.
- Background: PubMed 17367094Vadivelu N, Hines RL. Buprenorphine: a unique opioid with broad clinical applications. J Opioid Manag. 2007 Jan-Feb;3(1):49-58. doi: 10.5055/jom.2007.0038.
- Background: PubMed 215096Jasinski DR, Pevnick JS, Griffith JD. Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction. Arch Gen Psychiatry. 1978 Apr;35(4):501-16. doi: 10.1001/archpsyc.1978.01770280111012.
- Background: PubMed 27356522Walsh SL, Babalonis S. The Abuse Potential of Prescription Opioids in Humans-Closing in on the First Century of Research. Curr Top Behav Neurosci. 2017;34:33-58. doi: 10.1007/7854_2016_448.
- Background: PubMed 8181201Walsh SL, Preston KL, Stitzer ML, Cone EJ, Bigelow GE. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther. 1994 May;55(5):569-80. doi: 10.1038/clpt.1994.71.
- Background: PubMed 18567516Kress HG. Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine. Eur J Pain. 2009 Mar;13(3):219-30. doi: 10.1016/j.ejpain.2008.04.011. Epub 2008 Jun 24.
- Background: PubMed 33833565Pergolizzi JV Jr, Magnusson P, LeQuang JA, Breve F, Mitchell K, Chopra M, Varrassi G. Transdermal Buprenorphine for Acute Pain in the Clinical Setting: A Narrative Review. J Pain Res. 2021 Mar 31;14:871-879. doi: 10.2147/JPR.S280572. eCollection 2021.
- Background: PubMed 28405035Desai SN, Badiger SV, Tokur SB, Naik PA. Safety and efficacy of transdermal buprenorphine versus oral tramadol for the treatment of post-operative pain following surgery for fracture neck of femur: A prospective, randomised clinical study. Indian J Anaesth. 2017 Mar;61(3):225-229. doi: 10.4103/ija.IJA_208_16.
- Background: PubMed 26816973Arshad Z, Prakash R, Gautam S, Kumar S. Comparison between Transdermal Buprenorphine and Transdermal Fentanyl for Postoperative Pain Relief after Major Abdominal Surgeries. J Clin Diagn Res. 2015 Dec;9(12):UC01-4. doi: 10.7860/JCDR/2015/16327.6917. Epub 2015 Dec 1.
- Background: PubMed 28730328Kim HJ, Ahn HS, Nam Y, Chang BS, Lee CK, Yeom JS. Comparative study of the efficacy of transdermal buprenorphine patches and prolonged-release tramadol tablets for postoperative pain control after spinal fusion surgery: a prospective, randomized controlled non-inferiority trial. Eur Spine J. 2017 Nov;26(11):2961-2968. doi: 10.1007/s00586-017-5213-5. Epub 2017 Jul 20.
- Background: PubMed 32201109Londhe S, Patwardhan M, Shah R, Oak M. Efficacy and Safety of Buprenorphine Transdermal Patch for Immediate Postoperative Analgesia After Total Knee Arthroplasty Surgery. J Arthroplasty. 2020 Jun;35(6S):S178-S181. doi: 10.1016/j.arth.2020.02.015. Epub 2020 Feb 13.
- Background: PubMed 35928664Londhe SB, Patwardhan M, Shah RV, Oak M, Shah A, Antao N, Khot R. Comparison of Efficacy and Safety of Transdermal Buprenorphine Patch and Conventional Analgesics in Intra-capsular Femur Neck Fracture Post Hemiarthroplasty. Indian J Orthop. 2022 Jun 25;56(8):1363-1369. doi: 10.1007/s43465-022-00668-7. eCollection 2022 Aug.
- Individual participant dataSharing planned: Yes. After deidentification, all individual participant data may be shared.
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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.
Jenna Wilson, MD principal investigator
Washington University School of Medicine
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 Buprenorphine Transdermal System in people with Pain, Postoperative and Ankle Fracture Surgery, run by Jenna-Leigh Wilson 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 3 inclusion and 14 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 6 Apr 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. Some participants in this study may receive a placebo. 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 Noah J Harrison, MD, MMSc (314-459-1140, nharrison@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Morphine Milligram Equivalents of Full-agonist Opioid Consumed (time frame: Post-operative days 0-7. First post-operative clinic visit (approximately 3 weeks after surgery).). 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 NCT06949826, which also lists 32 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 6 Apr 2026.