Effect of Methylprednisolone on Immune Signaling in Hip-arthroplasty Patients

Effect of Preoperative Intravenous High Dose Methylprednisolone on Immune Signaling in Patients Scheduled for Total Hip-arthroplasty

The study evaluates the pathophysiological effects of a single dose Methylprednisolone administered prior to total hip-arthroplasty (THA) surgery. The investigators examine the effect on immune signaling and recovery after surgery.

Half of participants will receive intravenous Solu-Medrol 125 mg, while the other half will receive placebo.

The investigators hypothesize that the group receiving Methylprednisolone will experience a positive modulation of the immune response and an enhanced recovery.

Study Overview

• Status: Completed
• Conditions: Osteoarthrosis
• Intervention / Treatment: Drug: Isotonic Sodium Chloride; Drug: Methylprednisolone

Detailed Description

The anti-inflammatory effects of glucocorticoids are well known. The beneficial effects on postoperative pain, postoperative nausea and vomiting are well-documented.

Hip-arthroplasty surgery and the inflammatory stress response in general affect the potential of recovery. The basic physiological mechanisms behind restoration of recovery after surgery are still unresolved. The many different immune cells involved in the complex signal response enables wound healing and recovery, and the individual immune signal pattern might be able to predict recovery. The effects of glucocorticoids on this immune signal pattern is unknown and calls for further investigation.

The study is to be considered as exploratory. This study is embedded in a primary study registrated as: NCT02445898

For further details please view the EudraCT registration:

EudraCT nr.: 2015-000102-19

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen NV, Denmark, 2400
    • Copenhagen University Hospital, Bispebjerg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 53 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Osteoarthrosis
• Undergoing total unilateral hip-arthroplasty surgery
• Speak and understand Danish
• Have given informed content

Exclusion Criteria:

• Revision or bilateral hip-arthroplasty surgery
• General anaesthesia
• Allergy or intolerance towards Methylprednisolone
• Local or systemic infection
• Permanent systemic treatment with steroids within 30 days peroperatively
• Insulin-dependent diabetes
• Atrial fibrillation
• Neurological disease incl. Parkinsons
• Daily use of hypnotics or sedatives
• Alcohol abuse >35 units per week
• Active treatment of ulcer within 3 months preoperatively
• Cancer disease
• Autoimmune disease incl. rheumatoid arthritis
• Pregnant or breast feeding women
• Menopause <1 year

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Methylprednisolone; Preoperative single high dose of Solu-Medrol 125 mg iv.	Drug: Methylprednisolone; Comparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride (placebo); Other Names: Solu-Medrol
Placebo Comparator: Placebo; Preoperative single dose of isotonic Sodium Chloride	Drug: Isotonic Sodium Chloride; Placebo; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in concentration of plasma-STAT3 (Signal transducer and activator of transcription) from baseline to 48 hours after surgery	48 hours after surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in concentration of plasma-STAT3 from baseline to 14 days after surgery	14 days after surgery
Change in concentration of plasma-CREB (Adenosine 3',5'-monophosphate response element-binding protein) from baseline to 14 days after surgery	14 days after surgery
Change in concentration of plasma-NF-kB (Nuclear factor kB) from baseline to 14 days after surgery	14 days after surgery
Change in Surgical Recovery Scale score from baseline to 28 days after surgery	28 days after surgery
Change in modified WOMAC (Western Ontario and McMaster Universities Arthritis Index) score from baseline to 28 days after surgery	28 days after surgery

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Bispebjerg Hospital
• Investigators: Principal Investigator: Viktoria Lindberg-Larsen, MD, Section for Surgical Pathophysiology, Rigshospitalet

Publications and helpful links

General Publications

• Baigrie RJ, Lamont PM, Kwiatkowski D, Dallman MJ, Morris PJ. Systemic cytokine response after major surgery. Br J Surg. 1992 Aug;79(8):757-60. doi: 10.1002/bjs.1800790813.
• Stoecklein VM, Osuka A, Lederer JA. Trauma equals danger--damage control by the immune system. J Leukoc Biol. 2012 Sep;92(3):539-51. doi: 10.1189/jlb.0212072. Epub 2012 May 31.
• Wilmore DW. From Cuthbertson to fast-track surgery: 70 years of progress in reducing stress in surgical patients. Ann Surg. 2002 Nov;236(5):643-8. doi: 10.1097/00000658-200211000-00015.
• Giannoudis PV, Smith RM, Perry SL, Windsor AJ, Dickson RA, Bellamy MC. Immediate IL-10 expression following major orthopaedic trauma: relationship to anti-inflammatory response and subsequent development of sepsis. Intensive Care Med. 2000 Aug;26(8):1076-81. doi: 10.1007/s001340051320.
• Gaudilliere B, Fragiadakis GK, Bruggner RV, Nicolau M, Finck R, Tingle M, Silva J, Ganio EA, Yeh CG, Maloney WJ, Huddleston JI, Goodman SB, Davis MM, Bendall SC, Fantl WJ, Angst MS, Nolan GP. Clinical recovery from surgery correlates with single-cell immune signatures. Sci Transl Med. 2014 Sep 24;6(255):255ra131. doi: 10.1126/scitranslmed.3009701.
• Ganio EA, Stanley N, Lindberg-Larsen V, Einhaus J, Tsai AS, Verdonk F, Culos A, Ghaemi S, Rumer KK, Stelzer IA, Gaudilliere D, Tsai E, Fallahzadeh R, Choisy B, Kehlet H, Aghaeepour N, Angst MS, Gaudilliere B. Preferential inhibition of adaptive immune system dynamics by glucocorticoids in patients after acute surgical trauma. Nat Commun. 2020 Jul 27;11(1):3737. doi: 10.1038/s41467-020-17565-y. Erratum In: Nat Commun. 2020 Sep 3;11(1):4495.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: September 3, 2015
• First Submitted That Met QC Criteria: September 3, 2015
• First Posted (Estimate): September 7, 2015

Study Record Updates

• Last Update Posted (Estimate): January 18, 2017
• Last Update Submitted That Met QC Criteria: January 17, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Recovery; Glucocorticoids; Immune Signaling; Hip arthroplasty, total
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: HK_VL_08_2015a; 2015-000102-19 (EudraCT Number)