Improving Pain Management and Long Term Outcomes Following High Energy Orthopedic Trauma (Pain Study)
Overview
- Phase
- Phase 3
- Intervention
- placebo
- Conditions
- Orthopaedic Fractures
- Sponsor
- Major Extremity Trauma Research Consortium
- Enrollment
- 450
- Locations
- 17
- Primary Endpoint
- Opioid Utilization
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this study is to definitively resolve questions regarding the use of multimodal pharmacologic pain management for orthopedic trauma patients in the context of a multicenter, randomized clinical trial.
Also, as a significant proportion of this population develops chronic post traumatic osteoarthritis (PTOA), a sub-objective of this study is to examine the etiology and incidence of chronic pain and PTOA in this population.
Detailed Description
In this study, will test whether adjunctive analgesic therapy during the pre and peri-operative period, in addition to standard of care pain management, can improve overall pain control and pain related outcomes without increasing analgesic related side effects. Patients will be randomized into three treatment groups. The intervention will begin within 48 hours of admission and continue for up to the time of definitive fixation. Group 1: standard pain management, plus intravenous and oral placebo for up to 48 hours following definitive fixation. Group 2: standard pain management, plus intravenous NSAIDs (ketorolac) and oral placebo for up to 48 hours following definitive fixation. Group 3: standard pain management, plus intravenous placebo and oral pregabalin for up to 48 hours following definitive fixation. Specific Aim 1: Evaluate the effect of standard pain management (Group 1) vs. standard pain management plus peri-operative NSAIDs (Group 2 - meloxicam + ketorolac) in the treatment of severe limb fractures. Hypothesis 1a: When compared to patients who received standard of care pain management, patients treated with NSAIDs will: (1) have reduced post operative opioid utilization; (2) report reduced levels of persistent pain; and (3) have noninferior rates of surgery for nonunion. Hypothesis 1b: When compared to patients who received standard of care pain management, patients treated with NSAIDs will benefit from (1) improved post operative pain control; (2) improved pre operative pain control; (3) reduced lengths of stay; (4) reduced pain interference; (5) improved functional outcomes; (6) lower levels of depression and post-traumatic stress disorder (PTSD); (7) improved overall health status; and (8) have noninferior rates of analgesic treatment related side effects. Specific Aim 2: Evaluate the effect of standard pain management (Group 1) vs. standard pain management plus pre and peri-operative pregabalin (Group 3) in the treatment of severe limb fractures. Hypothesis2a : When compared to patients who received standard of care pain management, patients treated with pregabalin will: (1) have reduced post operative opioid utilization; (2) report reduced levels of persistent pain; and (3) have noninferior rates of surgery for nonunion. Hypothesis 2b: When compared to patients who received standard of care pain management, patients treated with pregabalin will benefit from (1) improved post operative pain control; (2) improved pre operative pain control; (3) reduced lengths of stay; (4) reduced pain interference; (5) improved functional outcomes; (6) lower levels of depression and post-traumatic stress disorder (PTSD); (7) improved overall health status; and (8) have noninferior rates of analgesic treatment related side effects. Specific Aim 3: Estimate the incremental cost effectiveness of each adjunctive analgesic therapy relative to standard of care analgesic therapy in the treatment of severe limb fractures. Costs will be estimated from both the health care provider perspective and the societal perspective. The time horizon for cost-effectiveness analysis will be based on the actual period of observation. Incremental cost-effectiveness ratios will be calculated for: (a) study group 2 (NSAIDS - meloxicam + ketorolac) relative to standard of care; and (b) study group 3 (pregabalin) relative to standard of care. For purpose of cost-effectiveness analysis, the effect will be measured as unit change in specific outcome metrics at up to 15 months (or longer period as available) compared to baseline. The following cost-effectiveness metrics, all relative to standard of care, will be reported: 1. incremental cost per unit change in the Brief Pain Inventory 2. incremental cost per unit change in the Short Muscular Function Assessment (SFMA) 3. incremental cost per unit change in health state preference ("utility") as derived from the VR-12. PTOA Pilot Study: Additional funding was received from NIH to conduct a pilot, observational study of post-traumatic osteoarthritis (PTOA), leveraging current resources of the Pain study. 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. Accomplishment of these aims will require (1) for all patients with ankle fractures in the Pain study: 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 and (2) for a subset of 60 pilon fracture patients enrolled in the Pain study for whom post-operative CT scans are not standard of care, obtain additional consent for completion of a study-funded post-operative CT scan and 24 month radiographic study
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with one of the following types of injuries:
- •Unilateral, Grade I \&II open or closed pilon (distal tibial plafond), calcaneus, talus fractures and Lisfranc dislocations requiring operative treatment with fixation; or
- •Unilateral, open (type I, II, or IIIA) ankle fractures with associated dislocation on presentation (OTA 44B3 or 44C) requiring operative treatment with fixation; or
- •Unilateral, open or closed distal and proximal humerus (OTA 11A-C and OTA 13 A-C); or
- •Open femoral shaft fracture (OTA 32 A-C; Gustilo Type I-IIIC) or open or closed supracondylar femur fractures (OTA 33 A-C); or
- •Open or closed tibial plateau or shaft fractures (OTA 42 A-C or 43 A-C)
- •Any combination of the above injuries which are surgically treated as a whole
- •Patients who present to the admitting hospital acutely or clinic following an initial assessment in the Emergency Department, for care up to 10 days following initial injury.
- •Patients 18-80 years old inclusive.
- •Patients who are English or Spanish competent.
Exclusion Criteria
- •Patients unable to provide informed consent.
- •Patients with chronic pain being presently treated with opioid or gabapentinoid prescription or any other alternative therapy.
- •Patients who are current IVDA
- •Patients with bilateral or ipsilateral injuries requiring surgery
- •Patients with other orthopedic or non-orthopedic injuries requiring operative intervention
- •Patients with severe osteopenia.
- •Patients who are skeletally immature (defined as less than 18 years of age or no radiographic evidence of epiphyseal closure).
- •Patients who are expected to have a post-surgical stay less than 24 hours.
- •Patients with a history of allergy to any drugs in the study.
- •Patients unable to swallow oral medications or without adequately functioning GI tract.
Arms & Interventions
Placebo
Standard pain management + perioperative intravenous placebo \& oral placebo. Control group will receive an oral dose of placebo up to two hours prior to surgery and twice daily for up to 48 hours following any surgery, in addition to an intravenous dose of placebo up to two hours prior to surgery and every 6 hours for up to 48 hours following surgery. All study medications will be in addition to standard of care pain medication. \*Previous preoperative protocol was removed due to difficulty of medication adherence and limited importance of preoperative regimen to the intervention overall.
Intervention: placebo
NSAID
Standard pain management + perioperative intravenous ketorolac \& oral placebo. The NSAID group will receive 30 mg of intravenous (IV) ketorolac (Ketorolac 30 mg/ml dose vial, NDC 00409-3795-01; manufacturer: Hospira) administered up to two hours prior to the procedure and every 6 hours for up to 48 hours following the procedure. In addition, as part of the perioperative protocol, patients will receive an oral dose of placebo up to two hours prior to the procedure and every 12 hours for up to 48 hours following the procedure. \*Previous preoperative protocol was removed due to difficulty of medication adherence and limited importance of preoperative regimen to the intervention overall.
Intervention: NSAID
Gabapentinoid
Standard pain management + perioperative intravenous placebo \& oral pregabalin. The Pregabalin group will receive an oral bolus dose of 300 mg of pregabalin up to two hours prior to the procedure and a 75 mg dose every 12 hours for up to 48 hours following the procedure. In addition, as part of the perioperative protocol, patients will receive an IV dose of placebo up to two hours prior to the procedure and every 6 hours for up to 48 hours following the procedure. \*Previous preoperative protocol was removed due to difficulty of medication adherence and limited importance of preoperative regimen to the intervention overall.
Intervention: Gabapentinoids
Outcomes
Primary Outcomes
Opioid Utilization
Time Frame: 1 year
Morphine equivalent opioid utilization during initial hospitalization through 48 hours following definitive fixation.
Persistent Pain
Time Frame: 1 year
Patient reported persistent pain states at standard of care visits 3, 6 and 12 months following hospital discharge. Measured using the Brief Pain Inventory (BPI) and an additional battery of questions to assess neuropathic pain (painDETECT).
Surgery for non-union
Time Frame: 1 year
Defined as non-prophylactic surgery for nonunion performed between six months and a year following initial hospital discharge.
Secondary Outcomes
- Post Surgical Pain Intensity(2 days)
- Pre Surgical Pain Intensity(2 days)
- Length of Index Hospitalization(1 year)
- Adverse Effects and Complications(2-3 weeks)
- Medical Costs(1 year)
- Functional Outcome(1 year)
- Generic Health Status(1 year)
- Post Traumatic Stress (PTSD)(1 year)
- Depressive Symptoms(1 year)
- Fracture Classification(1-2 years)
- Fracture Severity(1-2 years)