Ankle Fracture Surgery, Opioid Analgesia, Opioid Dependence, Opioid Use Disorder, Pain, Postoperative
Conditions
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
Brief 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. 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.
Interventions
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.
DRUGPlacebo Patch
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.
Sponsors
Jenna-Leigh Wilson
The Foundation for Barnes-Jewish Hospital
Washington University Institute of Clinical and Translational Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient is 18 years of age or older * Patient is undergoing single stage ORIF of an ankle fracture * Patient is English-speaking
Exclusion criteria
* 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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Morphine Milligram Equivalents of Full-agonist Opioid Consumed | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Pain Scores | Postoperative days 1-8, 21, 90. | 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. |
| Morphine Milligram Equivalents of Full-Agonist Opioids Administered in Perioperative Setting | Perioperative/Periprocedural | 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. |
| Adverse Effects Related to Opioid Medication | Post-operative days 1-8, 21. | 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. |
| Hospital Readmissions due to Uncontrolled Post-operative Pain | From patch application through post-operative day 21. | The investigators will track the number of hospital readmissions due to uncontrolled post-operative pain. |
| Emergency Department Presentations due to Uncontrolled Pain | From patch application through post-operative day 21. | The investigators will track the number of emergency department presentations, with a chief complaint of uncontrolled post-operative pain. |
| Emergency Department Presentations due to Opioid Toxicity | From patch application to post-operative day 21 | The researchers will track the number of presentations to the emergency department with a chief complaint of opioid toxicity. |
| Hospital Readmissions due to Opioid Toxicity | From patch application to post-operative day 21 | The researchers will track the number of hospital readmissions secondary to opioid toxicity. |
| Time from Surgery Completion to Discharge | Perioperative/periprocedural | For patients undergoing outpatient surgery, review of the electronic medical record will be performed to determine the time from surgery completion to discharge. |
| Hospital Length of Stay | From the completion of ankle fracture surgery to hospital discharge. | 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. |
| Number of Breakthrough Pain Episodes while Inpatient | Post-operative day 0 through hospital discharge | 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." |
| Quality of Recovery after Anesthesia 15-Question Survey | Post-operative day 7 | 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. |
| Telephone Calls and MyChart Messages to Clinic or Call Center with a Chief Complaint of Uncontrolled Pain | Post-operative days 0-21. | 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. |
| Opioid Medication Prescriptions - Number and Total Morphine Milligram Equivalents Prescribed | From the time of injury through post-operative day 90. | The researchers will review the electronic medical record to record the number of opioid medication prescriptions requested and filled by the patient. |
| Drug Liking and Economic Choice Survey | Post-operative days 7, 21, 90 | 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. |
| Patient Satisfaction with Post-operative Pain Control | Post-operative days 7, 21 | Patient satisfaction with their post-operative pain control will be recorded by questionnaire in the form of a Likert scale. |
| Rate of Persistent Opioid Use | Post-operative day 90 | Approximately three months after surgery, patients will record whether they are continuing to take opioids/narcotics for pain related to their ankle fracture surgery. |
| Prescription Pain Medication Misuse Short Form 7a Scores | Post-operative day 90 | 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. |
| Post-operative Complication Rate | Post-operative days 0-90 | The researchers will review the electronic medical record to the rate and type of post-operative complications after ankle fracture surgery. |
Countries
United States
Contacts
CONTACTNoah J Harrison, MD, MMSc
CONTACTJuanita Taylor, MPA, BS, RRT
PRINCIPAL_INVESTIGATORJenna Wilson, MD
Washington University School of Medicine
Outcome results
None listed