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The goal of this clinical trial is to learn if buprenorphine can treat pain in older adults who have broken bones. The main questions it aims to answer are:
Is buprenorphine as effective as opioids to treat pain? Are there less side effects with buprenorphine? Researchers will compare buprenorphine and hydromorphone to see if there are differences in pain control and side effects.
Participants will be given one of the two study drugs after breaking a bone and asked about their pain scores and side effects for the next 48 hours.
Older adults are prone to fractures but are less likely to receive adequate analgesia in the Emergency Department (ED)due to concerns for side effects including respiratory depression, sedation, delirium, and constipation, however untreated pain can induce delirium, decrease satisfaction, and impede functional recovery. Buprenorphine is a partial opioid agonist with analgesic properties, does not require dosing changes in renal or hepatic insufficiency, and may have a ceiling on respiratory depression. Prior studies have demonstrated similar or improved efficacy compared to full agonist opioids in treating acutely painful conditions, however older adults are underrepresented or excluded as a population in this research and have unique considerations due to polypharmacy, comorbidities, and aging physiology, leaving a gap in knowledge for this population.
This proposal will test the hypothesis that buprenorphine is a feasible intervention that is as effective as full-agonist opioids for the treatment of acute pain in older adults but with reduced adverse drug events, with the long-term goal to improve pain control in older adults in acute settings. Demonstrating safety of buprenorphine to manage older adults experiencing acute pain could improve emergency care, reduce adverse events associated with full agonist opioids, and improve patient satisfaction.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hydromorphone | Active Comparator | 0.25mg hydromorphone IV given every 15 minutes as needed for numerical pain score 4 or greater for a maximum of three doses |
|
| Buprenorphine | Experimental | 0.15mg buprenorphine IV given every 15 minutes as needed for numerical pain score 4 or greater for a maximum of three doses |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Buprenorphine 0.15 MG | Drug | given every 15 minutes as needed for numerical pain score 4 or greater for a maximum of three doses |
|
| Measure | Description | Time Frame |
|---|---|---|
| Difference in pain scores | Difference in pain scores measured on the numerical rating scale (scale of 0-10, with 10 being maximum pain and 0 being no pain), collected on arrival and measured at one hour and four hours after medication administration | 4 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with adverse events | Gastrointestinal symptoms such as nausea, vomiting, constipation, and diarrhea, including by inferring from antiemetic administration; respiratory depression; and delirium. Delirium will be assessed at least 8 hours after enrollment and first dose of medication and within 48 hours. Presence of delirium is determined by a positive Brief Confusional Assessment Method (bCAM) screen. Patients will also be interviewed about other adverse effects at the time of delirium assessment. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Katherine E Selman, MD | Contact | 856-342-2627 | selman-katherine@cooperhealth.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cooper University Hospital | Recruiting | Camden | New Jersey | 08103 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39024042 | Background | Selman K, Perelman S, Blatcher C, Fett D, Adams A, Roberts B. Buprenorphine for acute pain in older adults: a systematic review with meta-analysis. Pain Med. 2024 Jul 18:pnae064. doi: 10.1093/pm/pnae064. Online ahead of print. | |
| 37032687 | Background | Albaqami MS, Alqarni AA, Alabeesy MS, Alotaibi AN, Alharbi HA, Alshammari MM, Aldhfery AH. Buprenorphine for acute post-surgical pain: A systematic review and meta-analysis. Saudi J Anaesth. 2023 Jan-Mar;17(1):65-71. doi: 10.4103/sja.sja_822_22. Epub 2023 Jan 2. |
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There is not a plan to make individual participant data collected in this study available at this time given the small sample size. The authors may be contacted at any time to discuss further.
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| ID | Term |
|---|---|
| D050723 | Fractures, Bone |
| D000377 | Agnosia |
| ID | Term |
|---|---|
| D014947 | Wounds and Injuries |
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
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| ID | Term |
|---|---|
| D002047 | Buprenorphine |
| D004091 | Hydromorphone |
| ID | Term |
|---|---|
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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| Hydromorphone 0.25 mg IV | Drug | given every 15 minutes as needed for numerical pain score 4 or greater for a maximum of three doses |
|
| 48 hours |
| Number of patients requiring naloxone | Need for naloxone administration | 4 hours |
| Number of patients who receive rescue medications | Administration of rescue medications (yes/no) | 4 hours |
| Total oral morphine equivalents | Administered in the ED | 8 hours |
| Mortality | Mortality | 30 days |
| 29576108 | Background | White LD, Hodge A, Vlok R, Hurtado G, Eastern K, Melhuish TM. Efficacy and adverse effects of buprenorphine in acute pain management: systematic review and meta-analysis of randomised controlled trials. Br J Anaesth. 2018 Apr;120(4):668-678. doi: 10.1016/j.bja.2017.11.086. Epub 2017 Dec 2. |
| 22115823 | Background | Jalili M, Fathi M, Moradi-Lakeh M, Zehtabchi S. Sublingual buprenorphine in acute pain management: a double-blind randomized clinical trial. Ann Emerg Med. 2012 Apr;59(4):276-80. doi: 10.1016/j.annemergmed.2011.10.021. Epub 2011 Nov 23. |
| 37924855 | Background | Saini M, Samanta J, Kumar A, Choudhury A, Dhar J, Jafra A, Chauhan R, Muktesh G, Gupta P, Gupta V, Yadav TD, Kochhar R, Capurso G, De-Madaria E, Facciorusso A. Buprenorphine Versus Diclofenac for Pain Relief in Acute Pancreatitis: A Double-Blinded Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2024 Mar;22(3):532-541.e8. doi: 10.1016/j.cgh.2023.10.021. Epub 2023 Nov 3. |
| 16547090 | Background | Dahan A, Yassen A, Romberg R, Sarton E, Teppema L, Olofsen E, Danhof M. Buprenorphine induces ceiling in respiratory depression but not in analgesia. Br J Anaesth. 2006 May;96(5):627-32. doi: 10.1093/bja/ael051. Epub 2006 Mar 17. |
| 16764217 | Background | Boger RH. Renal impairment: a challenge for opioid treatment? The role of buprenorphine. Palliat Med. 2006;20 Suppl 1:s17-23. |
| 34079354 | Background | Hale M, Garofoli M, Raffa RB. Benefit-Risk Analysis of Buprenorphine for Pain Management. J Pain Res. 2021 May 24;14:1359-1369. doi: 10.2147/JPR.S305146. eCollection 2021. |
| 30531584 | Background | Coe MA, Lofwall MR, Walsh SL. Buprenorphine Pharmacology Review: Update on Transmucosal and Long-acting Formulations. J Addict Med. 2019 Mar/Apr;13(2):93-103. doi: 10.1097/ADM.0000000000000457. |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006572 |
| Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D009022 | Morphine Derivatives |