PAIN Study

PAIN Study


Improving Pain Management in High Energy Orthopaedic Trauma


Co-Principal Investigators: Dr. Renan Castillo and Dr. Srinivasa Raja

The objective of this study is to compare the efficacy of standard pain management vs. standard pain management combined with use of perioperative pregabalin (Lyrica) or ketorolac (Toradol) in the treatment of severe lower limb fractures.


Poorly controlled postoperative pain in orthopaedic trauma patients often leads to increased length of hospital stays, repeat hospitalizations, psychological distress, delayed functional recovery, and failure to return to work. Despite the importance of controlling postoperative pain, pain management for orthopaedic trauma patients remains inconsistent and often inadequate.


Perioperative pain management using non-steroidal anti-inflammatory drugs (NSAIDs) such as ketorolac (Toradol), and anticonvulsants such as pregabalin (Lyrica), has been found to substantially improve post-surgical pain control in numerous clinical settings. However, multi-modal perioperative pain management has not been widely used in orthopaedics due to conflicting data about increased risk of non-union, wound closure and bleeding complications.


Given the central role of pain management in the etiology of long-term disability following trauma, it is critical to definitively resolve this question in the context of a randomized clinical trial. This study focuses on isolated lower extremity trauma (many of whom have a single surgical encounter), but our findings should be easily extended to polytrauma populations. A critical next step in our research agenda will be to test the results of this study in a pragmatic trial in which multi-modal perioperative pain management is the standard for all surgical encounters in the care of the multiply injured patient.


The PAIN study is a three-arm, double blinded, randomized, placebo controlled Phase III clinical trial. Study participants with high energy lower limb fractures requiring operative fixation will be assigned via block randomization to one of the following three groups: (Group 1) standard pain management plus perioperative intravenous and oral placebo; (Group 2) standard pain management plus perioperative intravenous ketorolac (30 mg immediately before anesthesia and every 6 hours for 48 hours) and oral placebo; or (Group 3) standard pain management plus perioperative intravenous placebo and oral pregabalin (300 mg, 1 hour before surgery, 75 mg every 12 hours for 48 hours). Patients will be followed for 12 months to study unplanned readmissions for complications, and to assess pain, functional outcome, and medical costs. Analgesic treatment related side effects will also be assessed.


This study is being funded by DOD CDMRP METRC Consortium Award (W81XWH-10-2-0090).



PTOA Pilot Study


Characterizing Chronic Post Traumatic Osteoarthritis


Co-Principal Investigators: Dr. J. Lawrence Marsh and Don Anderson


The sub-objective of the Pain Study is to examine the etiology and incidence of chronic pain and PTOA in this population.


PTOA is an important outcome in the population to be enrolled in the Pain study. The aims of the PTOA Study are to: (1) measure the incidence of PTOA and chronic pain for up to 24 months following fracture reduction surgery and (2) quantify the extent to which fracture severity and post-reduction contact stress are related to the development of PTOA.  To achieve these aims, all patients in the Pain study will complete a PTOA survey at 12 months and at any subsequent visits that are conducted as part of standard of care and provide access to all standard of care imaging studies completed during the study period. Additionally, 60 patients with pilon fracture who enrolled in the Pain study for whom post-operative CT scans are not standard of care will be asked to provide consent for completion of a study-funded post-operative CT scan and 24 month radiographic study.


This is study is being funded by The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Award (R21 AR061808)