Clinical trial NCT05113901: Medrol Dosepak Taper for Delayed Post-op Recovery After TKA
Official title: Methylprednisolone Taper to Treat Delayed Post-Operative Recovery After Total Knee Arthroplasty: a Double-Blind Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Total Knee Arthroplasty
Keywords: Methylprednisolone
Delayed recover
range of motion
Lead sponsor: Rush University Medical Center
Sponsor class: OTHER
First posted: 2021-11-09
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: To evaluate the efficacy of a methylprednisolone taper on patients with decreased range of motion (ROM) or delayed recovery in the acute postoperative period following total knee arthroplasty (TKA).

Patients with decreased ROM or delayed recovery six weeks to three months post-TKA will improve ROM and patient-reported outcomes at two weeks post-treatment initiation of methylprednisolone taper, as compared to similar patients who receive a placebo taper.

Detailed description: Total knee arthroplasty (TKA) is one of the most performed and efficacious orthopaedic procedures, with an estimated 7 million people living with a total knee prosthesis in 2010.1 The number of annual TKAs is predicted to increase by 85% by 2030 and 143% by 2050, equating to 1.26 million2 and 1.5 million3 procedures per year, respectively. In recent studies, knee prostheses have demonstrated their efficacy in 10-, 20-, and 25-year survival rates of 96.1%, 89.7%4, and 82.3%5, respectively. Similarly, comparing functional and patient-reported outcomes before and after surgery have confirmed the high success rate achieved with this procedure.6-10 However, recovery following total knee arthroplasty (TKA) in the acute postoperative period is variable. Most clinical improvements are achieved within the first three months postoperatively but can continue up to one year.11 There is currently a paucity of data evaluating the efficacy of oral corticosteroids in the six-week to three-month postoperative period in slowly recovering patients.

Few treatments have been studied for patients who fail to achieve early range of motion or pain reduction milestones in the perioperative period. Periarticular and systemic corticosteroids improve pain and function in the immediate postoperative period, without an increase in adverse events.12-16 Additional doses of corticosteroids administered at 24 and 48 hours postoperatively have demonstrated greater improvements in pain and ROM compared to perioperative administration, with no difference in complication rates.17-20 However, few studies have evaluated the use of oral corticosteroids within a multimodal pain management regimen. Gardiner et al. evaluated low-dose steroids 10 days immediately following lumbar laminectomy and/or discectomy, in addition to a standard opioid regimen, and reported decreased subjective pain scores.21 Gottshalk et al. reported decreased patient reported pain from postoperative days 4-7 in early published results of a randomized controlled trial investigating administration of a methylprednisolone taper immediately following distal radius repair.22 Importantly, the current literature demonstrates low- and short-dose corticosteroids are safe.23 Intraoperative corticosteroids have been shown to improve pain and function in the acute postoperative period, and additional doses in the immediate postoperative period can potentiate and prolong this beneficiary effect, without increasing adverse events. Therefore, a methylprednisolone taper six weeks post-TKA may benefit patients experiencing decreased ROM or delayed recovery, including residual pain.

Following TKA, care is taken to control pain, swelling, and stiffness, all of which may contribute to delayed recovery. For instance, more than 20% of TKA patients develop postoperative stiffness,24 known as arthrofibrosis, accounting for an estimated 28% of 90-day hospital readmissions.25 In treating patients with delayed recovery, corticosteroids are of particular interest because of its potent anti-inflammatory effect, evidenced by its ability to decrease postoperative levels of IL-6 and CRP.15 Corticosteroids block prostaglandin synthesis, which is responsible for sensitizing nociceptive pain receptors, and reduce vascular permeability, which causes edema following surgery.26, 27 Therefore, by reducing pain and edema, corticosteroids may allow for more effective physical therapy sessions and more rapid improvement in ROM and recovery following TKA.

To the best of our knowledge, this is the first study to investigate the utility of a methylprednisolone taper six weeks to three months postoperatively following TKA. The authors present a double-blinded, randomized-controlled trial evaluating the role of a methylprednisolone taper on patients with decreased ROM or delayed recovery in the acute postoperative period.

Eligibility criteria: Inclusion Criteria:

* Any patient undergoing primary TKA with a diagnosis of osteoarthritis
* ≥ 18 years old
* ROM \<90° by 3 weeks postoperatively without improvement to \>90° by 6 weeks
* Requiring a 30-pill oxycodone refill
* NSAID allergy
* Thigh circumference discrepancy \>2cm between legs from 3 to 6 weeks
* Defense and Veterans Pain Rating Scale (DVPRS) \> 5 between 3 and 6 weeks
* Willingness to undergo randomization

Exclusion Criteria:

* Reported chronic corticosteroid or opiate use
* Suspected or confirmed periprosthetic joint infection
* Revision TKA
* Primary diagnosis other than osteoarthritis, including avascular necrosis, fracture, or post-traumatic arthritis
* American Society of Anesthesiologists (ASA) score ≥ 4
* Reported history of liver or renal disease
* Uncontrolled diabetes
* Immunosuppression
* ≤ 18 years old
* Inability to take oral medications
* Unable to provide consent

Primary outcomes:
measure: Range of Motion in Degrees at Pre and Post Treatment
timeFrame: Baseline, Week 6 Following Treatment
Secondary outcomes:
measure: Patient Reported Outcome Measures: Post Treatment Pain Scores (6 Weeks)
timeFrame: 6 weeks post treatment
measure: Patient Reported Outcome Measures: Pre Treatment Pain Scores Using Knee Society Scores
timeFrame: pre treatment
measure: Patient Reported Outcome Measures: Post Treatment Pain Scores
timeFrame: 3 weeks post treatment
measure: Patient Reported Outcome Measures: Post Treatment Pain Scores
timeFrame: 6 weeks post treatment
measure: Patient Reported Outcome Measures:(Immediate) Post Treatment Pain Scores
timeFrame: Days 1 through 6 following treatment
measure: Patient Reported Outcome Measures: Overall Assessment of Knee After Surgery and Treatment
timeFrame: pre treatment
measure: Patient Reported Outcome Measures: Overall Assessment of Knee After Surgery and Treatment
timeFrame: 6 weeks after treatment
measure: Patient Reported Outcome Measures: Overall Assessment of Knee Before Treatment
timeFrame: pre treatment
measure: Patient Reported Outcome Measures: Overall Assessment of Knee 6 Weeks After Treatment
timeFrame: 6 weeks after treatment
measure: Patient Reported Outcome Measures: Overall Assessment of Knee Before Treatment
timeFrame: pre treatment
measure: Patient Reported Outcome Measures: Overall Assessment of Knee 6 Weeks After Treatment
timeFrame: 6 weeks after treatment
measure: Patient Reported Outcome Measures: Overall Assessment of Knee Prior to Treatment
timeFrame: pre treatment
measure: Patient Reported Outcome Measures: Overall Assessment of Knee 6 Wks After Treatment
timeFrame: 6 weeks after treatment
measure: Patient Reported Outcome Measures: Overall Assessment of Knee Prior to Treatment
timeFrame: pre treatment
measure: Patient Reported Outcome Measures: Overall Assessment of Knee 6 Weeks After Treatment
timeFrame: 6 weeks after treatment
measure: Number of Participants With Complications Following Treatment
timeFrame: within 90 days after initial total knee arthroplasty
measure: Adverse Events or Outcomes Outside of Manipulations Under Anesthesia
timeFrame: within 90 days after initial total knee arthroplasty
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University medical Center
state: Illinois
Study officials:
References:
citation: Inacio MCS, Paxton EW, Graves SE, Namba RS, Nemes S. Projected increase in total knee arthroplasty in the United States - an alternative projection model. Osteoarthritis Cartilage. 2017 Nov;25(11):1797-1803. doi: 10.1016/j.joca.2017.07.022. Epub 2017 Aug 8.
citation: Maradit Kremers H, Larson DR, Crowson CS, Kremers WK, Washington RE, Steiner CA, Jiranek WA, Berry DJ. Prevalence of Total Hip and Knee Replacement in the United States. J Bone Joint Surg Am. 2015 Sep 2;97(17):1386-97. doi: 10.2106/JBJS.N.01141.
citation: Sloan M, Premkumar A, Sheth NP. Projected Volume of Primary Total Joint Arthroplasty in the U.S., 2014 to 2030. J Bone Joint Surg Am. 2018 Sep 5;100(17):1455-1460. doi: 10.2106/JBJS.17.01617.
citation: Bayliss LE, Culliford D, Monk AP, Glyn-Jones S, Prieto-Alhambra D, Judge A, Cooper C, Carr AJ, Arden NK, Beard DJ, Price AJ. The effect of patient age at intervention on risk of implant revision after total replacement of the hip or knee: a population-based cohort study. Lancet. 2017 Apr 8;389(10077):1424-1430. doi: 10.1016/S0140-6736(17)30059-4. Epub 2017 Feb 14.
citation: Evans JT, Evans JP, Walker RW, Blom AW, Whitehouse MR, Sayers A. How long does a hip replacement last? A systematic review and meta-analysis of case series and national registry reports with more than 15 years of follow-up. Lancet. 2019 Feb 16;393(10172):647-654. doi: 10.1016/S0140-6736(18)31665-9. Epub 2019 Feb 14.
citation: Callahan CM, Drake BG, Heck DA, Dittus RS. Patient outcomes following tricompartmental total knee replacement. A meta-analysis. JAMA. 1994 May 4;271(17):1349-57.
citation: Ethgen O, Bruyere O, Richy F, Dardennes C, Reginster JY. Health-related quality of life in total hip and total knee arthroplasty. A qualitative and systematic review of the literature. J Bone Joint Surg Am. 2004 May;86(5):963-74. doi: 10.2106/00004623-200405000-00012.
citation: Heath EL, Ackerman IN, Cashman K, Lorimer M, Graves SE, Harris IA. Patient-reported outcomes after hip and knee arthroplasty : results from a large national registry. Bone Jt Open. 2021 Jun;2(6):422-432. doi: 10.1302/2633-1462.26.BJO-2021-0053.R1.
citation: Shan L, Shan B, Suzuki A, Nouh F, Saxena A. Intermediate and long-term quality of life after total knee replacement: a systematic review and meta-analysis. J Bone Joint Surg Am. 2015 Jan 21;97(2):156-68. doi: 10.2106/JBJS.M.00372.
citation: Kane RL, Saleh KJ, Wilt TJ, Bershadsky B. The functional outcomes of total knee arthroplasty. J Bone Joint Surg Am. 2005 Aug;87(8):1719-24. doi: 10.2106/JBJS.D.02714.
citation: Kagan R, Anderson MB, Christensen JC, Peters CL, Gililland JM, Pelt CE. The Recovery Curve for the Patient-Reported Outcomes Measurement Information System Patient-Reported Physical Function and Pain Interference Computerized Adaptive Tests After Primary Total Knee Arthroplasty. J Arthroplasty. 2018 Aug;33(8):2471-2474. doi: 10.1016/j.arth.2018.03.020. Epub 2018 Mar 17.
citation: Deng Z, Li Y, Storm GR, Kotian RN, Sun X, Lei G, Gao S, Lu W. The efficiency and safety of steroid addition to multimodal cocktail periarticular injection in knee joint arthroplasty: a meta-analysis of randomized controlled trials. Sci Rep. 2019 May 7;9(1):7031. doi: 10.1038/s41598-019-43540-9.
citation: Li Q, Mu G, Liu X, Chen M. Efficacy of additional corticosteroids to multimodal cocktail periarticular injection in total knee arthroplasty: a meta-analysis of randomized controlled trials. J Orthop Surg Res. 2021 Jan 22;16(1):77. doi: 10.1186/s13018-020-02144-0.
citation: Mohammad HR, Hamilton TW, Strickland L, Trivella M, Murray D, Pandit H. Perioperative adjuvant corticosteroids for postoperative analgesia in knee arthroplasty. Acta Orthop. 2018 Feb;89(1):71-76. doi: 10.1080/17453674.2017.1391409. Epub 2017 Oct 25.
citation: Yue C, Wei R, Liu Y. Perioperative systemic steroid for rapid recovery in total knee and hip arthroplasty: a systematic review and meta-analysis of randomized trials. J Orthop Surg Res. 2017 Jun 27;12(1):100. doi: 10.1186/s13018-017-0601-4.
citation: Lex JR, Edwards TC, Packer TW, Jones GG, Ravi B. Perioperative Systemic Dexamethasone Reduces Length of Stay in Total Joint Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Arthroplasty. 2021 Mar;36(3):1168-1186. doi: 10.1016/j.arth.2020.10.010. Epub 2020 Oct 16.
citation: Backes JR, Bentley JC, Politi JR, Chambers BT. Dexamethasone reduces length of hospitalization and improves postoperative pain and nausea after total joint arthroplasty: a prospective, randomized controlled trial. J Arthroplasty. 2013 Sep;28(8 Suppl):11-7. doi: 10.1016/j.arth.2013.05.041. Epub 2013 Aug 9.
citation: Kim JK, Ro DH, Lee HJ, Park JY, Han HS, Lee MC. Efficacy of Systemic Steroid Use Given One Day After Total Knee Arthroplasty for Pain and Nausea: A Randomized Controlled Study. J Arthroplasty. 2020 Jan;35(1):69-75. doi: 10.1016/j.arth.2019.08.026. Epub 2019 Aug 19.
citation: Lei Y, Huang Z, Huang Q, Huang W, Pei F. Repeat Doses of Dexamethasone up to 48 Hours Further Reduce Pain and Inflammation After Total Hip Arthroplasty: A Randomized Controlled Trial. J Arthroplasty. 2020 Nov;35(11):3223-3229. doi: 10.1016/j.arth.2020.06.023. Epub 2020 Jun 17.
citation: Xu H, Zhang S, Xie J, Lei Y, Cao G, Pei F. Multiple Doses of Perioperative Dexamethasone Further Improve Clinical Outcomes After Total Knee Arthroplasty: A Prospective, Randomized, Controlled Study. J Arthroplasty. 2018 Nov;33(11):3448-3454. doi: 10.1016/j.arth.2018.06.031. Epub 2018 Jul 4.
citation: Gardiner D, McShane BJ, Kerr M, et al. Low-Dose Steroids to Decrease Postoperative Pain and Opioid Use. Journal for nurse practitioners. 2020;16(7):523-527. doi:10.1016/j.nurpra.2020.04.017
citation: Gottschalk M, Dawes A, Farley K, et al. Postoperative Methylprednisolone Taper Course for Distal Radius Fractures: Early Results of a Randomized Controlled Trial. Orthopaedic Proceedings; 2020:21
citation: Salerno A, Hermann R. Efficacy and safety of steroid use for postoperative pain relief. Update and review of the medical literature. J Bone Joint Surg Am. 2006 Jun;88(6):1361-72. doi: 10.2106/JBJS.D.03018.
citation: Issa K, Banerjee S, Kester MA, Khanuja HS, Delanois RE, Mont MA. The effect of timing of manipulation under anesthesia to improve range of motion and functional outcomes following total knee arthroplasty. J Bone Joint Surg Am. 2014 Aug 20;96(16):1349-57. doi: 10.2106/JBJS.M.00899.
citation: Schairer WW, Vail TP, Bozic KJ. What are the rates and causes of hospital readmission after total knee arthroplasty? Clin Orthop Relat Res. 2014 Jan;472(1):181-7. doi: 10.1007/s11999-013-3030-7.
citation: Leppert W, Buss T. The role of corticosteroids in the treatment of pain in cancer patients. Curr Pain Headache Rep. 2012 Aug;16(4):307-13. doi: 10.1007/s11916-012-0273-z.
citation: Vyvey M. Steroids as pain relief adjuvants. Can Fam Physician. 2010 Dec;56(12):1295-7, e415.
citation: Prvu Bettger J, Green CL, Holmes DN, Chokshi A, Mather RC 3rd, Hoch BT, de Leon AJ, Aluisio F, Seyler TM, Del Gaizo DJ, Chiavetta J, Webb L, Miller V, Smith JM, Peterson ED. Effects of Virtual Exercise Rehabilitation In-Home Therapy Compared with Traditional Care After Total Knee Arthroplasty: VERITAS, a Randomized Controlled Trial. J Bone Joint Surg Am. 2020 Jan 15;102(2):101-109. doi: 10.2106/JBJS.19.00695.
citation: Guzik A, Druzbicki M, Wolan-Nieroda A, Turolla A, Kiper P. Estimating Minimal Clinically Important Differences for Knee Range of Motion after Stroke. J Clin Med. 2020 Oct 15;9(10):3305. doi: 10.3390/jcm9103305.
citation: Research Programs. Accessed July 22, 2021. https://www.kneesociety.org/research-programs
citation: Huscher D, Thiele K, Gromnica-Ihle E, Hein G, Demary W, Dreher R, Zink A, Buttgereit F. Dose-related patterns of glucocorticoid-induced side effects. Ann Rheum Dis. 2009 Jul;68(7):1119-24. doi: 10.1136/ard.2008.092163. Epub 2008 Aug 6.
citation: Saag KG, Koehnke R, Caldwell JR, Brasington R, Burmeister LF, Zimmerman B, Kohler JA, Furst DE. Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med. 1994 Feb;96(2):115-23. doi: 10.1016/0002-9343(94)90131-7.
citation: Goldberg H, Firtch W, Tyburski M, Pressman A, Ackerson L, Hamilton L, Smith W, Carver R, Maratukulam A, Won LA, Carragee E, Avins AL. Oral steroids for acute radiculopathy due to a herniated lumbar disk: a randomized clinical trial. JAMA. 2015 May 19;313(19):1915-23. doi: 10.1001/jama.2015.4468.
citation: Bartlett R, Hartle AJ. Routine use of dexamethasone for postoperative nausea and vomiting: the case against. Anaesthesia. 2013 Sep;68(9):892-6. doi: 10.1111/anae.12309. Epub 2013 Jul 15. No abstract available.
citation: Feeley AA, Feeley TB, Feeley IH, Sheehan E. Postoperative Infection Risk in Total Joint Arthroplasty After Perioperative IV Corticosteroid Administration: A Systematic Review and Meta-Analysis of Comparative Studies. J Arthroplasty. 2021 Aug;36(8):3042-3053. doi: 10.1016/j.arth.2021.03.057. Epub 2021 Apr 24.
citation: Sauerland S, Nagelschmidt M, Mallmann P, Neugebauer EA. Risks and benefits of preoperative high dose methylprednisolone in surgical patients: a systematic review. Drug Saf. 2000 Nov;23(5):449-61. doi: 10.2165/00002018-200023050-00007.
citation: Dilisio MF. Osteonecrosis following short-term, low-dose oral corticosteroids: a population-based study of 24 million patients. Orthopedics. 2014 Jul;37(7):e631-6. doi: 10.3928/01477447-20140626-54.
citation: Madanagopal SG, Kovaleski JE, Pearsall AW 4th. Survey of short-term oral corticosteroid administration by orthopaedic physicians in college and high school athletes. J Sports Sci Med. 2009 Mar 1;8(1):37-44. eCollection 2009.