Clinical trial NCT02542592: Effect of Methylprednisolone on Immune Signaling in Hip-arthroplasty Patients
Official title: Effect of Preoperative Intravenous High Dose Methylprednisolone on Immune Signaling in Patients Scheduled for Total Hip-arthroplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Osteoarthrosis
Keywords: Glucocorticoids
Immune Signaling
Recovery
Hip arthroplasty, total
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Bispebjerg Hospital
First posted: 2015-09-07
Enrollment: 64
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Change in concentration of plasma-STAT3 (Signal transducer and activator of transcription) from baseline to 48 hours after surgery
timeFrame: 48 hours after surgery
Secondary outcomes:
measure: Change in concentration of plasma-STAT3 from baseline to 14 days after surgery
timeFrame: 14 days after surgery
measure: Change in concentration of plasma-CREB (Adenosine 3',5'-monophosphate response element-binding protein) from baseline to 14 days after surgery
timeFrame: 14 days after surgery
measure: Change in concentration of plasma-NF-kB (Nuclear factor kB) from baseline to 14 days after surgery
timeFrame: 14 days after surgery
measure: Change in Surgical Recovery Scale score from baseline to 28 days after surgery
timeFrame: 28 days after surgery
measure: Change in modified WOMAC (Western Ontario and McMaster Universities Arthritis Index) score from baseline to 28 days after surgery
timeFrame: 28 days after surgery
Other outcomes:
Locations:
city: Copenhagen NV
country: Denmark
facility: Copenhagen University Hospital, Bispebjerg
Study officials:
affiliation: Section for Surgical Pathophysiology, Rigshospitalet
name: Viktoria Lindberg-Larsen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.