Knee Osteoarthritis Treatment With Zilretta vs. Kenalog in the Context of Type II Diabetes

Summary

A Phase 2 Randomized Study to Evaluate the Effects of triamcinolone acetonide extended-release (TA-ER; Zilretta) vs. triamcinolone acetonide immediate-release (TA-IR; Kenalog) on Blood Glucose Levels in Diabetic Subjects with Knee Osteoarthritis. Subjects should have Type 2 Diabetes Mellitus (T2DM) with HbA1C ≤9 that is managed without insulin and have been diagnosed with symptomatic unilateral or bilateral osteoarthritis (OA) of the knee, based on clinical and radiological criteria (if bilateral, then a target knee will be selected).Total study duration for individual subject will be about 4 months, which includes 3 weeks of Screening period, 10 days of pretreatment phase, treatment day, and 12 weeks of post-treatment period.

Timeline

Start

2024-08-16

Primary completion

2026-12-16

Completion

2027-01-16

Publications

• Background Russell SJ, Sala R, Conaghan PG, Habib G, Vo Q, Manning R, Kivitz A, Davis Y, Lufkin J, Johnson JR, Kelley S, Bodick N. Triamcinolone acetonide extended-release in patients with osteoarthritis and type 2 diabetes: a randomized, phase 2 study. Rheumatology (Oxford). 2018 Dec 1;57(12):2235-2241. doi: 10.1093/rheumatology/key265.
• Background Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986 Aug;29(8):1039-49. doi: 10.1002/art.1780290816.
• Background Arbuckle RA, Humphrey L, Vardeva K, Arondekar B, Danten-Viala M, Scott JA, Snoek FJ. Psychometric evaluation of the Diabetes Symptom Checklist-Revised (DSC-R)--a measure of symptom distress. Value Health. 2009 Nov-Dec;12(8):1168-75. doi: 10.1111/j.1524-4733.2009.00571.x. Epub 2009 Jun 24.
• Background Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, Kraus VB, Lohmander LS, Abbott JH, Bhandari M, Blanco FJ, Espinosa R, Haugen IK, Lin J, Mandl LA, Moilanen E, Nakamura N, Snyder-Mackler L, Trojian T, Underwood M, McAlindon TE. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019 Nov;27(11):1578-1589. doi: 10.1016/j.joca.2019.06.011. Epub 2019 Jul 3.
• Background Bashir MA, Ray R, Sarda P, Li S, Corbett S. Determination of a safe INR for joint injections in patients taking warfarin. Ann R Coll Surg Engl. 2015 Nov;97(8):589-91. doi: 10.1308/rcsann.2015.0044.
• Background Choudhry MN, Malik RA, Charalambous CP. Blood Glucose Levels Following Intra-Articular Steroid Injections in Patients with Diabetes: A Systematic Review. JBJS Rev. 2016 Mar 22;4(3):e5. doi: 10.2106/JBJS.RVW.O.00029.
• Background Derendorf H, Mollmann H, Gruner A, Haack D, Gyselby G. Pharmacokinetics and pharmacodynamics of glucocorticoid suspensions after intra-articular administration. Clin Pharmacol Ther. 1986 Mar;39(3):313-7. doi: 10.1038/clpt.1986.45.
• Background Johnston PC, Lansang MC, Chatterjee S, Kennedy L. Intra-articular glucocorticoid injections and their effect on hypothalamic-pituitary-adrenal (HPA)-axis function. Endocrine. 2015 Mar;48(2):410-6. doi: 10.1007/s12020-014-0409-5. Epub 2014 Sep 3.
• Background Kompel AJ, Roemer FW, Murakami AM, Diaz LE, Crema MD, Guermazi A. Intra-articular Corticosteroid Injections in the Hip and Knee: Perhaps Not as Safe as We Thought? Radiology. 2019 Dec;293(3):656-663. doi: 10.1148/radiol.2019190341. Epub 2019 Oct 15.
• Background Mader R, Lavi I, Luboshitzky R. Evaluation of the pituitary-adrenal axis function following single intraarticular injection of methylprednisolone. Arthritis Rheum. 2005 Mar;52(3):924-8. doi: 10.1002/art.20884.
• Background Patel J, Schneider BJ, Smith CC; Spine Intervention Society's Patient Safety Committee. Fact Finders for Patient Safety: Intra-Articular Corticosteroid Injections and Hyperglycemia. Pain Med. 2018 May 1;19(5):1091-1092. doi: 10.1093/pm/pnx303. No abstract available.
• Background Tamez-Perez HE, Quintanilla-Flores DL, Rodriguez-Gutierrez R, Gonzalez-Gonzalez JG, Tamez-Pena AL. Steroid hyperglycemia: Prevalence, early detection and therapeutic recommendations: A narrative review. World J Diabetes. 2015 Jul 25;6(8):1073-81. doi: 10.4239/wjd.v6.i8.1073.
• Background Young P, Homlar KC. Extreme Postinjection Flare in Response to Intra-Articular Triamcinolone Acetonide (Kenalog). Am J Orthop (Belle Mead NJ). 2016 Mar-Apr;45(3):E108-11.

Drugs

Indications