Effectiveness of Corticosteroid vs. Ketorolac Shoulder Injections: A Prospective Double-Blinded Randomized Trial

Rotator Cuff Tendinitis Clinical Trial

Official title:

Effectiveness of Corticosteroid vs. Ketorolac Shoulder Injections: A Prospective Double-Blinded Randomized Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04115644
• Other study ID #: STU 092014-097
• Status: Terminated
• Phase: Phase 4
• Start date: May 1, 2017
• Est. completion date: September 14, 2017

Study information

• Verified date: November 2023
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the functional outcomes of patients with shoulder pathology treated with either ketorolac or corticosteroid injections, in a randomized double-blinded study. Investigators will compare the effectiveness of ketorolac compared to corticosteroid. Specific Aim 1: Hypothesis 1: Injection of the shoulder (in the subacromial space) with Ketorolac will be more effective than corticosteroid injection for the treatment of a variety of shoulder pathologies. The risks associated with this study primarily concern adverse reactions to the study drugs. The drugs used in this study are not narcotics or habit-forming but can have side effects. The patient's physician will screen for any heart, intestinal, or kidney disease or condition that would increase the chance for the patient to have an unwanted side effect.

Description:

The proposed study is a three arm, double-blinded, prospective randomized controlled clinical trial with follow-up immediately after the injection and at day 2, and weeks 1, 2, 4, 6, and 12. In this study investigators will compare the effectiveness of ketorolac compared to corticosteroid. Subjects being seen for a rotator cuff injury will be randomized into one of three treatment groups pertaining to their pathology. The intervention will begin once the subject has consented and answered the Baseline Outcome Shoulder Questionnaire. The Baseline Outcome Questionnaire consists of the Visual Analog Score, American Shoulder and Elbow Score, Single Assessment Numeric Evaluation, Pittsburgh Sleep Quality Index, Short Form-12, and questions pertaining to patient characteristics, injury characteristics, co-morbidities, patient history, medications, and demographics.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 82
• Est. completion date: September 14, 2017
• Est. primary completion date: September 14, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Rotator Cuff Tendinitis
• Atraumatic Rotator Cuff Tear
• Rotator Cuff Tear Arthropathy
• Subjects who speak English

Exclusion Criteria:

• Age: < 18 years old
• Prior Shoulder Surgery
• Fracture
• Acute Traumatic Rotator Cuff Tear
• Infection
• Uncontrolled Diabetes Mellitus (HbA1c >8)
• Recent Prior Shoulder Injection in either the Subacromial space
• Workers Compensation
• History of Gastric Ulcers
• Tumor Involving the Shoulder Region
• Prior history of gastrointestinal bleeding, allergic reactions, impaired renal function, seizures or cardiac arrhythmias
• Subject unable to provide informed consent
• Subjects who don't speak English
• Patients who are pregnant or lactating at time of screening or are of child bearing age
• Patients currently receiving an aspirin, NSAID regimen or any other anti-inflammatory agents that could affect inflammation response.
• Patients with any bleeding disorders.
• Patients with severe renal failure.
• Patients likely to have severe problems maintaining follow-up, including patients diagnosed with severe psychiatric conditions, patients who live too far outside the hospital's catchment area, patients who are incarcerated and patients who have unstable housing situations.
• Patients who are allergic to aspirin, ketorolac tromethamine and other NSAIDs

Related Conditions & MeSH terms

• Full Thickness Rotator Cuff Tear
• Rotator Cuff Injuries
• Rotator Cuff Tendinitis
• Tendinopathy

Intervention

Drug:
• Ketorolac
Group 2 (ketorolac): will receive an injection of 3 cc 0.25% Marcaine without epinephrine and 2 cc ketorolac 30 mg/ml
• Marcaine (placebo)
Group 1 (control): will receive an injection of 5 cc 0.25% Marcaine without epinephrine
• Kenalog
Group 3 (kenalog): 4 cc 0.25% Marcaine without epinephrine and 1 cc triamcinolone.

Locations

Country	Name	City	State
United States	John Hopkins Shoulder & Sports Medicine	Baltimore	Maryland
United States	University of Texas Southwestern Medical Center	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Michael Khazzam

Country where clinical trial is conducted

United States, 

References & Publications (37)

Adebajo AO, Nash P, Hazleman BL. A prospective double blind dummy placebo controlled study comparing triamcinolone hexacetonide injection with oral diclofenac 50 mg TDS in patients with rotator cuff tendinitis. J Rheumatol. 1990 Sep;17(9):1207-10. — View Citation

Alvarez CM, Litchfield R, Jackowski D, Griffin S, Kirkley A. A prospective, double-blind, randomized clinical trial comparing subacromial injection of betamethasone and xylocaine to xylocaine alone in chronic rotator cuff tendinosis. Am J Sports Med. 2005 Feb;33(2):255-62. doi: 10.1177/0363546504267345. — View Citation

Balasubramaniam P, Prathap K. The effect of injection of hydrocortisone into rabbit calcaneal tendons. J Bone Joint Surg Br. 1972 Nov;54(4):729-34. No abstract available. — View Citation

Blair B, Rokito AS, Cuomo F, Jarolem K, Zuckerman JD. Efficacy of injections of corticosteroids for subacromial impingement syndrome. J Bone Joint Surg Am. 1996 Nov;78(11):1685-9. doi: 10.2106/00004623-199611000-00007. — View Citation

Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4. — View Citation

Choi WD, Cho DH, Hong YH, Noh JH, Lee ZI, Byun SD. Effects of subacromial bursa injection with corticosteroid and hyaluronidase according to dosage. Ann Rehabil Med. 2013 Oct;37(5):668-74. doi: 10.5535/arm.2013.37.5.668. Epub 2013 Oct 29. — View Citation

Dogan N, Erdem AF, Gundogdu C, Kursad H, Kizilkaya M. The effects of ketorolac and morphine on articular cartilage and synovium in the rabbit knee joint. Can J Physiol Pharmacol. 2004 Jul;82(7):502-5. doi: 10.1139/y04-066. — View Citation

Gerstenfeld LC, Al-Ghawas M, Alkhiary YM, Cullinane DM, Krall EA, Fitch JL, Webb EG, Thiede MA, Einhorn TA. Selective and nonselective cyclooxygenase-2 inhibitors and experimental fracture-healing. Reversibility of effects after short-term treatment. J Bone Joint Surg Am. 2007 Jan;89(1):114-25. doi: 10.2106/JBJS.F.00495. — View Citation

Glassman SD, Rose SM, Dimar JR, Puno RM, Campbell MJ, Johnson JR. The effect of postoperative nonsteroidal anti-inflammatory drug administration on spinal fusion. Spine (Phila Pa 1976). 1998 Apr 1;23(7):834-8. doi: 10.1097/00007632-199804010-00020. — View Citation

Gould D, Kelly D, Goldstone L, Gammon J. Examining the validity of pressure ulcer risk assessment scales: developing and using illustrated patient simulations to collect the data. J Clin Nurs. 2001 Sep;10(5):697-706. doi: 10.1046/j.1365-2702.2001.00525.x. — View Citation

Hawker, G.A., et al. Measures of Adult Pain. 2011; Available from: http://onlinelibrary.wiley.com/doi/10.1002/acr.20543/pdf

Haws MJ, Kucan JO, Roth AC, Suchy H, Brown RE. The effects of chronic ketorolac tromethamine (toradol) on wound healing. Ann Plast Surg. 1996 Aug;37(2):147-51. doi: 10.1097/00000637-199608000-00005. — View Citation

Ho ML, Chang JK, Wang GJ. Effects of ketorolac on bone repair: A radiographic study in modeled demineralized bone matrix grafted rabbits. Pharmacology. 1998 Sep;57(3):148-59. doi: 10.1159/000028236. — View Citation

Itzkowitch D, Ginsberg F, Leon M, Bernard V, Appelboom T. Peri-articular injection of tenoxicam for painful shoulders: a double-blind, placebo controlled trial. Clin Rheumatol. 1996 Nov;15(6):604-9. doi: 10.1007/BF02238552. — View Citation

Jean YH, Wen ZH, Chang YC, Hsieh SP, Tang CC, Wang YH, Wong CS. Intra-articular injection of the cyclooxygenase-2 inhibitor parecoxib attenuates osteoarthritis progression in anterior cruciate ligament-transected knee in rats: role of excitatory amino acids. Osteoarthritis Cartilage. 2007 Jun;15(6):638-45. doi: 10.1016/j.joca.2006.11.008. Epub 2007 Jan 2. — View Citation

Kapetanos G. The effect of the local corticosteroids on the healing and biomechanical properties of the partially injured tendon. Clin Orthop Relat Res. 1982 Mar;(163):170-9. — View Citation

Karthikeyan S, Kwong HT, Upadhyay PK, Parsons N, Drew SJ, Griffin D. A double-blind randomised controlled study comparing subacromial injection of tenoxicam or methylprednisolone in patients with subacromial impingement. J Bone Joint Surg Br. 2010 Jan;92(1):77-82. doi: 10.1302/0301-620X.92B1.22137. — View Citation

Kenalog: Drug Summary. Available from: http://www.pdr.net/drug-summary/kenalog-40?druglabelid=2494

Kenaolg Package Insert. July 2014; Available from: http://packageinserts.bms.com/pi/pi_kenalog-40.pdf.

Ketorolac: Drug Class and Mechanism. 2014; Available from: http://www.medicinenet.com/ketorolac-oral/article.htm

Koester MC, Dunn WR, Kuhn JE, Spindler KP. The efficacy of subacromial corticosteroid injection in the treatment of rotator cuff disease: A systematic review. J Am Acad Orthop Surg. 2007 Jan;15(1):3-11. doi: 10.5435/00124635-200701000-00002. — View Citation

Marder RA, Kim SH, Labson JD, Hunter JC. Injection of the subacromial bursa in patients with rotator cuff syndrome: a prospective, randomized study comparing the effectiveness of different routes. J Bone Joint Surg Am. 2012 Aug 15;94(16):1442-7. doi: 10.2106/JBJS.K.00534. — View Citation

Michener LA, McClure PW, Sennett BJ. American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, patient self-report section: reliability, validity, and responsiveness. J Shoulder Elbow Surg. 2002 Nov-Dec;11(6):587-94. doi: 10.1067/mse.2002.127096. — View Citation

Min KS, St Pierre P, Ryan PM, Marchant BG, Wilson CJ, Arrington ED. A double-blind randomized controlled trial comparing the effects of subacromial injection with corticosteroid versus NSAID in patients with shoulder impingement syndrome. J Shoulder Elbow Surg. 2013 May;22(5):595-601. doi: 10.1016/j.jse.2012.08.026. Epub 2012 Nov 22. — View Citation

Mullis BH, Copland ST, Weinhold PS, Miclau T, Lester GE, Bos GD. Effect of COX-2 inhibitors and non-steroidal anti-inflammatory drugs on a mouse fracture model. Injury. 2006 Sep;37(9):827-37. doi: 10.1016/j.injury.2005.12.018. Epub 2006 Feb 23. — View Citation

O'Keefe RJ, Tiyapatanaputi P, Xie C, Li TF, Clark C, Zuscik MJ, Chen D, Drissi H, Schwarz E, Zhang X. COX-2 has a critical role during incorporation of structural bone allografts. Ann N Y Acad Sci. 2006 Apr;1068:532-42. doi: 10.1196/annals.1346.012. — View Citation

Ogbru, O. Marcaine - Drug Class and Mechanism. 6/27/2014; Available from: http://www.medicinenet.com/bupivicaine-injection/article.htm.

Oxlund H. The influence of a local injection of cortisol on the mechanical properties of tendons and ligaments and the indirect effect on skin. Acta Orthop Scand. 1980 Apr;51(2):231-8. doi: 10.3109/17453678008990791. — View Citation

Park SY, Moon SH, Park MS, Oh KS, Lee HM. The effects of ketorolac injected via patient controlled analgesia postoperatively on spinal fusion. Yonsei Med J. 2005 Apr 30;46(2):245-51. doi: 10.3349/ymj.2005.46.2.245. — View Citation

Penning LI, de Bie RA, Walenkamp GH. The effectiveness of injections of hyaluronic acid or corticosteroid in patients with subacromial impingement: a three-arm randomised controlled trial. J Bone Joint Surg Br. 2012 Sep;94(9):1246-52. doi: 10.1302/0301-620X.94B9.28750. — View Citation

Pradhan BB, Tatsumi RL, Gallina J, Kuhns CA, Wang JC, Dawson EG. Ketorolac and spinal fusion: does the perioperative use of ketorolac really inhibit spinal fusion? Spine (Phila Pa 1976). 2008 Sep 1;33(19):2079-82. doi: 10.1097/BRS.0b013e31818396f4. — View Citation

Prisk V, Huard J. Muscle injuries and repair: the role of prostaglandins and inflammation. Histol Histopathol. 2003 Oct;18(4):1243-56. doi: 10.14670/HH-18.1243. — View Citation

Radi ZA, Khan NK. Effects of cyclooxygenase inhibition on bone, tendon, and ligament healing. Inflamm Res. 2005 Sep;54(9):358-66. doi: 10.1007/s00011-005-1367-4. — View Citation

Richards RR, An KN, Bigliani LU, Friedman RJ, Gartsman GM, Gristina AG, Iannotti JP, Mow VC, Sidles JA, Zuckerman JD. A standardized method for the assessment of shoulder function. J Shoulder Elbow Surg. 1994 Nov;3(6):347-52. doi: 10.1016/S1058-2746(09)80019-0. Epub 2009 Feb 13. — View Citation

Sucato DJ, Lovejoy JF, Agrawal S, Elerson E, Nelson T, McClung A. Postoperative ketorolac does not predispose to pseudoarthrosis following posterior spinal fusion and instrumentation for adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2008 May 1;33(10):1119-24. doi: 10.1097/BRS.0b013e31816f6a2a. — View Citation

Wei AS, Callaci JJ, Juknelis D, Marra G, Tonino P, Freedman KB, Wezeman FH. The effect of corticosteroid on collagen expression in injured rotator cuff tendon. J Bone Joint Surg Am. 2006 Jun;88(6):1331-8. doi: 10.2106/JBJS.E.00806. — View Citation

Wiggins ME, Fadale PD, Barrach H, Ehrlich MG, Walsh WR. Healing characteristics of a type I collagenous structure treated with corticosteroids. Am J Sports Med. 1994 Mar-Apr;22(2):279-88. doi: 10.1177/036354659402200221. — View Citation

* Note: There are 37 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual Analog Scale	Pain as measured by the Visual Analog Scale prior to first injection. The visual analog scale is a 0-10 scale, 0 being no pain, 10 being unbearable pain.	Baseline - pre-injection
Primary	Visual Analog Scale	Pain as measured by the Visual Analog Scale after first injection. The visual analog scale is a 0-10 scale, 0 being no pain, 10 being unbearable pain.	Baseline - immediately after the injection
Primary	Visual Analog Scale	Pain as measured by the Visual Analog Scale. The visual analog scale is a 0-10 scale, 0 being no pain, 10 being unbearable pain.	Day 2
Primary	Visual Analog Scale	Pain as measured by the Visual Analog Scale. The visual analog scale is a 0-10 scale, 0 being no pain, 10 being unbearable pain.	Week 1
Primary	Visual Analog Scale	Pain as measured by the Visual Analog Scale. The visual analog scale is a 0-10 scale, 0 being no pain, 10 being unbearable pain.	Week 2
Primary	Visual Analog Scale	Pain as measured by the Visual Analog Scale. The visual analog scale is a 0-10 scale, 0 being no pain, 10 being unbearable pain.	Week 4
Primary	Visual Analog Scale	Pain as measured by the Visual Analog Scale. The visual analog scale is a 0-10 scale, 0 being no pain, 10 being unbearable pain.	Week 6
Primary	Visual Analog Scale	Pain as measured by the Visual Analog Scale. The visual analog scale is a 0-10 scale, 0 being no pain, 10 being unbearable pain.	Week 12
Primary	American Shoulder and Elbow Score (ASES)	Pain, instability, and activities of daily living as measured by the American Shoulder and Elbow Score. The ASES is a 100-point scale that consists of two dimensions: pain and activities of daily living. One pain scale is worth 50 points, and activities of daily living worth 50 points. A higher score indicates a better outcome.	Baseline
Primary	American Shoulder and Elbow Score (ASES)	Pain, instability, and activities of daily living as measured by the American Shoulder and Elbow Score. The ASES is a 100-point scale that consists of two dimensions: pain and activities of daily living. One pain scale is worth 50 points, and activities of daily living worth 50 points. A higher score indicates a better outcome.	Week 6
Primary	American Shoulder and Elbow Score (ASES)	Pain, instability, and activities of daily living as measured by the American Shoulder and Elbow Score. The ASES is a 100-point scale that consists of two dimensions: pain and activities of daily living. One pain scale is worth 50 points, and activities of daily living worth 50 points. A higher score indicates a better outcome.	Week 12
Secondary	Single Assessment Numeric Evaluation (SANE)	Measure the patient's self-reported function on a scale of 0 to 100	Baseline
Secondary	Single Assessment Numeric Evaluation (SANE)	Measure the patient's self-reported function on a scale of 0 to 100	Week 6
Secondary	Single Assessment Numeric Evaluation (SANE)	Measure the patient's self-reported function on a scale of 0 to 100	Week 12
Secondary	Pittsburgh Sleep Quality Index (PSQI)	Sleep quality as measured by the Pittsburgh Sleep Quality Index	Baseline
Secondary	Pittsburgh Sleep Quality Index (PSQI)	Sleep quality as measured by the Pittsburgh Sleep Quality Index	Week 6
Secondary	Pittsburgh Sleep Quality Index (PSQI)	Sleep quality as measured by the Pittsburgh Sleep Quality Index	Week 12
Secondary	Short Form 12 (SF-12)	General health survey as measured by the Short Form 12 (SF-12)	Baseline
Secondary	Short Form 12 (SF-12)	General health survey as measured by the Short Form 12 (SF-12)	Week 6
Secondary	Short Form 12 (SF-12)	General health survey as measured by the Short Form 12 (SF-12)	Week 12